Ignite Creation Date:
2024-05-06 @ 1:08 AM
Last Modification Date:
2024-10-26 @ 10:59 AM
Study NCT ID:
NCT01739205
Status:
COMPLETED
Last Update Posted:
2012-12-03
First Post:
2012-11-27
Brief Title:
Biobehavioral Bases Management of Type 2 Diabetes
Sponsor:
University of Miami
Organization:
University of Miami
Study Overview
Official Title:
Biobehavioral Bases Management of Type 2 Diabetes
Status:
COMPLETED
Status Verified Date:
2012-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
CALM-D
Brief Summary:
The major objective of this project is to determine if compared to Standard Care SC a Community Approach to Lifestyle Modification for Diabetes CALM-D program including diet exercise and coping skills training can decrease depression weight and HbA1c and improve medication adherence in low income primarily Black and LatinoHispanic depressed overweight Type 2 diabetic patients seen in a large comprehensive community health center Type 2 diabetes is a major risk factor for coronary heart disease CHD Obesity poor glycemic control depression low socioeconomic status SES and being a member of a racialethnic minority group all increase this risk
The project will compare 100 CALM-D and 100 SC participants Following 3 run-in sessions assessment sessions to determine eligibility given to both SC and CALM-D participants SC patients will be treated in accordance with ADA Clinical Practice Guidelines 2005 and also assessed by project staff at baseline 6 months and 1 year The CALM-D participants will receive 2 individual stress management and lifestyle sessions followed by 2 weekly group sessions Then 4 bi-weekly sessions will be followed by 9 monthly sessions for a total of 17 sessions Secondary objectives of the project are to determine if compared to SC CALM-D can improve glucose tolerance to challenge insulin resistance oxidative stress inflammation procoagulation lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology psychosocial functioning and health quality of life As many of the participants will already have been prescribed aspirin statins oral hypoglycemics and other medications an important objective of the project will be to assess the extent to which improved adherence to medications - a goal of the CALM-D program - can account for improved intervention effects
The project will compare 100 CALM-D and 100 SC participants Following 3 run-in sessions assessment sessions to determine eligibility given to both SC and CALM-D participants SC patients will be treated in accordance with ADA Clinical Practice Guidelines 2005 and also assessed by project staff at baseline 6 months and 1 year The CALM-D participants will receive 2 individual stress management and lifestyle sessions followed by 2 weekly group sessions Then 4 bi-weekly sessions will be followed by 9 monthly sessions for a total of 17 sessions Secondary objectives of the project are to determine if compared to SC CALM-D can improve glucose tolerance to challenge insulin resistance oxidative stress inflammation procoagulation lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology psychosocial functioning and health quality of life As many of the participants will already have been prescribed aspirin statins oral hypoglycemics and other medications an important objective of the project will be to assess the extent to which improved adherence to medications - a goal of the CALM-D program - can account for improved intervention effects
Detailed Description:
This project will be conducted on type 2 diabetic patients Patients meeting eligibility criteria will be randomized to SC or the CALM-D condition which includes diet and exercise counseling and coping skills training that in part is intended to facilitate medication adherence Both CALM-D and SC patients will be prescribed antidepressant as well as other medications
Because patient retention and adherence to protocol will be a major emphasis in this project we intend to use a 3 session run-in prior to randomization Patients who appear to be medically eligible meet study criteria for major depression and who express willingness to participate return for a session in which the patient completes a medical history form undergoes a brief physical exam takes a maximum exercise stress test is given a standardized dietary assessment and is taught how to use a food diary and activity monitor At the beginning of the third run-in session the patient returns the completed food diary and data from the activity monitor is recorded The patient then takes a 2 hour oral glucose tolerance test OGTT during which time he or she answers questions about health habits psychosocial functioning and health quality of life After a brief rest and snack the patient is escorted to the Ultrasound Laboratory for assessment of echocardiography carotid artery imaging and brachial artery endothelial functioning Patients who satisfactorily complete all three run-in sessions meet eligibility requirements and are interested in participating are then asked to provide informed consent and are randomized into the CALM-D or SC conditions
Randomization will be implemented using a stratified randomized block design Eight strata will be designated on the basis of age 50 vs 50 years severity of depression 24 vs 24 on the HRSD and glycemic control 8 vs HbA1c at baseline Within each stratum random sequences will be generated in blocks of sizes 2 4 or 6 The block size will also be randomly chosen In this manner the resulting sequence will look purely random but will be fairly closely balanced with respect to the critical variables of age depression and severity of diabetes Piantadosi 1997 Elements in the random sequences will be paired with the subject number of participants assigned to each stratum The number of sequences generated for each stratum will vary depending on the number of eligible participants in that stratum These sequences will be concealed until the treatment conditions are actually assigned
The SC patients will be treated in accordance with ADA Clinical Practice Guidelines 2005 which will include at least 2 HbA1c tests lipid profile test for microalbuminuria dilated retinal eye exam complete foot exam and influenza immunization each year plus prescribed aspirin therapy and a screen for readiness to stop smoking if they smoke Smokers are encouraged to stop using ADA recommendations in the Guidelines In addition each patients physician will receive after baseline 6 months and 1 year a report including OGTT insulin resistance oxidative stress inflammation lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology psychosocial functioning and health quality of life Participants in the CALM-D condition will receive all of the above but also 2 individual counseling sessions on a getting started being active losing weight and managing stress and b negative thoughts and emotions including a discussion of ways to curb emotional eating Following the 2 individual sessions there will be 2 weekly group sessions followed by 4 bi-weekly sessions and then 9 monthly sessions Each session in CALM-D will be 1 hour long and will include deep breathing relaxation 5 min homework review including medication adherence activity level and fat and caloric intake 10 min session topics and homework assignment 45 min The group topics include such issues as Wheres the FatThree Ways to Eat Less Fat and Taking Your MedicationsStress and You Although participants and interventionists will be aware of the patients treatment assignment all staff who collect verify or classify end point data or follow-up assessments will be masked as much as possible
The primary outcomes of the study will be a depression b weight and waist circumference c HbA1c and d medication adherence Secondary outcomes will include a glucose tolerance b insulin resistance c inflammation d fibrinolysis e lipid profile f oxidative stress g endothelial function h resting blood pressure i cardiac and vascular function j cardiac morphology k psychosocial functioning and l health quality of life The above variables will be assessed at baseline after 6 months and after 1 year Data will be analyzed using mixed-model analyses to determine change over time as a function of experimental condition This will be done using the PROC Mixed module of SAS software Littell Milliken Stroup Wolfinger 1996 This methodology is useful for intent to treat analyses in that it does not require complete data across multiple time points
Approximately 50 of the patients we intend to recruit are likely to be LatinoHispanic based on our previous experience most of these LatinoHispanic participants will prefer to speak write and answer questions in Spanish All of the instruments proposed are available in Spanish To a large extent the CALM-D intervention developed for the present project is based on both the DPP and ENRICHD protocols We recognize of course that language and ethnicity are not the same However there is a great deal of diversity among LatinoHispanics in the patient sample we have enrolled from the Jackson Health Care System including Cubans Colombians Puerto Ricans Nicaraguans Dominicans Mexicans Peruvians and Guatamalans among others
During the 2 hour OGTT the participant will complete questionnaires including a Medical History Form eg demographics risk factors comorbid illnesses medications b health habits eg smoking alcohol use physical activity c psychosocial functioning eg BDI DISH and d health quality of life In addition to providing measures of blood glucose and plasma insulin the blood draw will permit assessment of HbA1c inflammation fibrinolysis and lipids After the OGTT the assessor will provide the participant with a snack and allow for a brief rest period Then the RD will conduct a dietary assessment and record the data from the activity monitor The participant will then be escorted to the Ultrasound Laboratory for assessment of echocardiography carotid artery imaging and brachial artery endothelial function At the completion of the session the participant will report to the Assessors review the days events be thanked for participating and paid 100 reimbursement for his or her time and transportation
Physical measures Activity monitor Between the second and third week of the run-in Baseline and 1 week before the 6 month and 12 month assessments all participants will wear activity monitors for physical activity The participants will also complete the Blair 1984 questionnaire for the same one-week period Participants in the CALM-D condition will be reminded one week prior to each of 17 intervention sessions to wear the accelerometer daily and bring it to the next session We intend to use the New Lifestyle NL-2000 activity monitor This device weighs 25 ounce count steps and estimates calories burned The caloric estimate subtracts calories burned in maintenance and adjusts for intensity based upon steps per unit of time This device has a 7 day automatic memory that starts each midnight at zero
Albuminuria Albumin and creatinine will be measured during the 2nd run-inassessment Baseline session by urine sample see Core B Serum creatinine will also be measured Patients will be excluded if there is evidence of renal disease ie urine dipstick protein 4 serum creatinine 14 mgdL in women or 15 mgdL in men or currently receiving dialysis In those patients who meet criteria for entry into the study the incidence and progression of microalbuminuria or greater level of excretion will be assessed using an albumincreatinine ratio at both 6 month and 12 month follow-up Serum creatinine will also be measured at these times
Cardiorespiratory fitness Fitness will be evaluated at Baseline second run-inassessment session and at 6- and 12-month follow-up with a maximal treadmill test see Core C The Baseline symptom-limited maximum stress test represents the current standard of care for an exercise prescription The primary measure for assessing change will be change in maximal oxygen uptake VO2 max Heart rate ECG changes blood pressure and VO2 max will be determined during the exercise test For the maximum exercise stress tests the participant will be continued on any prescribed medication for cardiovascular disease The following 3 abnormalities classify an individual at moderate to high risk for cardiac complication during exercise and will result in study exclusion 1 2 or more previous myocardial infarctions 2 previous episode of primary cardiac arrest 3 exercise capacity 6 METS 4 ischemic horizontal or downsloping ST segment depression 40 mm or 5 angina during exercise see Core C for details
Diabetes control CALM-D will include measurement of HbA1c fasting glucose and response to oral glucose challenge at Baseline run-inassessment session 2 and at both 6- and 12-month follow-up Patients will be excluded at Baseline if HbA1c 11
Psychosocial measures Beck Depression Inventory BDI The BDI Beck 1967 taps several domains of depression Of the 21 items on the scale 11 deal with cognition 2 with affect 2 with overt behavior 1 with interpersonal symptoms and 5 with somatic symptoms In overweight type 2 diabetic patients somatic symptoms may reflect physical disease processes eg fatigue or inflammation rather than primary depression For this reason subanalyses separating out effects of the intervention on somatic vs nonsomatic items will be important The BDI has been used extensively in English Spanish and various European speaking populations with internal reliability between α 85-93 eg Sanz Vázquez 1993
Perceived Stress Scale PSS The PSS Cohen S Williamson G 1988 is a 10 item scale that measures the degree to which situations in peoples lives are perceived as stressful unpredictable uncontrollable overwhelming and has good reliability α 85
Cook-Medley Hostility Scale Ho The Ho scale Cook Medley 1954 is composed of 50 true-false items taken from the MMPI that measures cynicism and mistrust of others and has adequate test -retest reliability internal consistency and construct validity Smith 1992 It has been shown in a number of large scale prospective studies to be associated with increased risk for CHD Miller et al 1996
Coping The Brief Cope Carver 1997 will be used to assess coping strategies that may be moderating CALM-D intervention effects This instrument has demonstrated high internal consistency adequate stability over time and substantial convergent validity Based on our previous studies using the Cope we shall be looking at the following 2 item subscales 1 active coping 2 using emotional support 3 using instrumental support and 4 behavioral disengagement Subscales 1 2 and 3 will also be used as a composite measure
Perceived Social Support Scale PSSS The PSSS Blumenthal et al 1987 is a 12-item scale that addresses perceived support from family friends and significant others It has established reliability and is related to CHD
Health quality of life Health Status Questionnaire Short Form SF-36 The SF-36 Ware Sherbourne 1992 is a 36-item instrument with 8 multi-item scales 1 physical functioning 2 social functioning 3 role limitations due to physical health problems 4 role limitations due to personal or emotional problems 5 general mental health 6 vitality 7 bodily pain and 8 general health perceptions Subscale reliabilities have been above 08 in multiple population studies conducted on adults It has successfully been used to evaluate functional status in depressed chronically ill and healthy individuals Wells et al 1989
Intervention In the present project all participants a will meet diagnostic criteria for major depressive disorder unless currently prescribed an antidepressant medication and have both a prior diagnosis of depression and current BDI score 11 It should be noted that a patient with type 2 diabetes has approximately the same risk of an MI as a patient who has already had an MI but does not have diabetes Haffner et al 1998
During the study half of the participants all of whom are depressed will be randomized to the CALM-D intervention and half into standard care
The CALM-D intervention consists of 17 sessions The first 4 sessions meet weekly Sessions 1 and 2 are individual sessions in which counselor and participant get to know one another and build rapport They also provide the participant with the opportunity to ask questions describe potential barriers and express reservations Sessions 3 and 4 which also meet weekly encourage participants to get to know one another and deal with issues concerning diet and medication adherence After the first 4 weekly sessions participants meet for 4 biweekly sessions followed by 9 monthly sessions One week prior to each bi-weekly and monthly session the therapist will call to remind the participant of the next meeting and request that the participant wear the accelerometer and fill-out the food diary daily until the upcoming session Immediately prior to each CALM-D intervention session the participant is weighed accelerometer results are recorded and the food diary is turned in Upon initial randomization into the intervention condition and again during session 1 the participant is told that he or she is invited to ask a partner family member living in the household or a friend to come to the intervention sessions The topic for each session are shown in Table D39
Table D29 Session Topic Weekly
1 I Welcome to the CALM-D Program Getting Started Being Active Losing Weight and Managing Stress
2 I Negative Thoughts and Emotions
3 G Wheres the FatThree Ways to Eat Less Fat
4 G Taking Your MedicationsStress and You Bi weekly
5 G Move Those MusclesBeing Active A Way of Life
6 G Challenging and Changing Negative Thoughts
7 G Healthy Eating
8 G Problem Solving Monthly
9 G Four Keys to Healthy Eating Out
10 G Social SupportCommunication
11 G Take Charge of Whats Around YouTip the Calorie Balance
12 G The Slippery Slope of Lifestyle Change
13 G Jump Start Your Activity Plan
14 G AssertivenessMake Social Cues Work for You
15 G You Can Manage Stress
16 G Life Goals
17 G Ways to Stay Motivated Abbreviations I Individual session G Group session
The objectives of the intervention are for participants to a lose 7 of their weight through healthy eating b do 25 hrs of brisk physical activity each wk eg walk briskly for 30 min 5x per week c manage stress better eg through coping strategies deep breathing and d always take their medication Participants are also taught how to fill out a food diary
At the outset of the intervention the counselor will discuss the effects of excess weight on diabetes and how complications of diabetes can be decreased with improved diet and increased activity level In terms of diet participants are taught how to use a fat counter and read labels weigh and measure foods eat less fat change eating habits to better match the food pyramid choose healthy eating behaviors make healthy food choices when eating out and relate calorie balance to weight loss To promote physical activity participants discuss current activity level benefits of being more active possible activities that can be undertaken regularly how to overcome barriers to activity and ways to prevent injury The participants also learn how to use an accelerometer Later in the program patients learn the definition of aerobic fitness and its relationship to frequency intensity time and type of activity Ways to add interest and variety to activity plans are also discussed
As a precursor to learning how to manage stress participants are taught how to identify types of negative thinking and the relationships among thoughts emotions and ways to curb emotional eating The counselor also stimulates discussion on how failure to take prescribed antidepressants can lead to mood related physical inactivity and other unhealthy health behaviors eg excessive alcohol use overeating Participants are taught how to assess if negative thoughts are accurate replace inaccurate negative thoughts with accurate thoughts handle situations in which one cant fix the problem identify sources of emotional and tangible support and use them effectively prevent stress and cope with stress The intervention also deals with the need for handling lapses and relapses regarding diet physical activity depression and medication adherence Participants are taught to identify high-risk situations and early warning signs as well as how to use adaptive coping strategies
Specific strategies to achieve the weight loss goal A weight loss goal of 7 is set which should lead to a loss of 7-21 lbs within 24 weeks Participants will be weighed in private at each session and this will be recorded on the weight graph in each participants notebook Participants will be encouraged if possible to weigh themselves outside of the study venues A total fat intake goal will be set based upon 25 total calories from fat A total caloric intake goal will also be set Daily self-monitoring of food intake fat and calories will be requested of participants with food measuring tools and a fat and calorie counter will be provided A more simplified form of self-monitoring will be provided for participants with very limited reading and math skills
Specific strategies to achieve the physical activity goal A physical activity goal of 700 kilocalories per week or 25 hours of moderate activity is set in a step-wise fashion to be reached in 5-weeks Another goal is to reach 10000 steps per week recorded on the accelerometer Participants will be asked to maintain daily physical activity records in their diaries based on information from the accelerometer Sites at which physical activity can be safely and effectively undertaken will be identified for each participant based on their residence
Specific strategies to achieve the medication adherence goals Participants list all of the medications they take and keep this list in a notebook The purpose of each medication is explained to the participant as well as the reasons for always taking the medication each day as prescribed Participants are encouraged to develop the habit of taking their medications as prescribed at the same time each day Discussions about handling weekends going on vacation etc are discussed during intervention sessions Reminders about taking medications are offered at each session and each phone call Refills of medications are carefully tracked When participants report that they are running low on a medication they are encouraged to obtain refills promptly Reported side effects of medications are carefully monitored and attempts made to determine if the side effects are easily remedied eg take just before bedtime take with breakfast or are due to not following instructions correctly If necessary the participant is referred to his or her physician for consideration of a change in medication
Counselors and their supervision The counselors we propose to use in this intervention are licensed PhD Clinical psychologists who have served as counselors in the post-MI project and in the adolescent intervention project of the present program project Supervision is carried out by Dr Patrice Saab PhD who helped to develop both of our intervention protocols and received supervisory training from the Beck Institute in conjunction with the ENRICHD trial and by Dr Ronald Goldberg MD who was the PI of the Miami site for the DPP Based on weekly reviews of audiotaped sessions Dr Saab will determine using a protocol check list intervention adherence to the manual point out any drift or lack of fidelity to the protocol and offer professional suggestions on how to remediate problems Using standards developed in DPP Dr Goldberg will assure that counselors are adhering to protocol with regard to such issues as using a fat counter weighing and measuring foods using the food pyramid and supervising exercise and food diary homework Weekly supervision is an institutionalized component of all of our intervention programs
Study hypotheses related to Primary aims and their association In accordance with the specific aims it is hypothesized that
From Primary Aim 1 Participants enrolled in the CALM-D intervention will show significantly greater improvement in BDI depression scores compared to participants in the SC condition
The greater improvement in BDI score in the CALM-D than in the SC condition will be mediated by increased medication adherence and improved coping skills by CALM-D participants
From Primary Aim 2 Participants enrolled in the CALM-D intervention will show significantly greater weight loss than participants in the SC condition
The greater weight loss in the CALM-D than in the SC condition will be mediated by decreased depression increased adherence to dietary instructions and increased physical activity
From Primary Aim 3 Participants enrolled in the CALM-D intervention will show significantly lower HbA1c in the SC condition
The greater decrease in HbA1c in the CALM-D than in the SC condition will be mediated by greater weight loss improved nutrition and increased exercise
From Primary Aim 4 Participants enrolled in the CALM-D intervention will show significantly greater medication adherence than participants in the SC condition
The greater increase in anti-depressant medication adherence in the CALM-D than in the SC condition will be mediated by improved coping skills and an increase in perceived social support
The greater increase in adherence to prescribed medications other than anti-depressants in the CALM-D than in the SC condition will be mediated by decreased depression and improved coping skills
Study hypotheses related to secondary aims In accordance with the studys secondary aims it is hypothesized that
Participants enrolled in the CALM-D intervention will show significantly improved insulin sensitivity and tolerance to oral glucose challenge compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved procoagulation and endothelial function and decreased inflammation and oxidative stress compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved lipid profiles compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show lower resting blood pressure and improved cardiac and vascular function as well as cardiac morphology compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved psychosocial functioning compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved health quality of life compared to participants in the SC condition
The greater improvement in improved tolerance to oral glucose challenge insulin sensitivity procoagulation oxidative stress lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology and health quality of life will each be associated with decreased waist circumference
Statistical analyses Preliminary analyses All data will be inspected employing quality control procedures Descriptive statistics will be computed for every study variable to ensure that all data values are within expected ranges and to eliminate any data errors that may have occurred If needed in the event that some of our variables are not normally distributed we will transform these variables using log transformations or use non-parametric statistics A mixed model analysis program using SAS Proc Mixed for growth models will be used to assess our 4 primary hypotheses Missing data will be handled using the full information likelihood algorithm which uses all the data available for all participants To assess our secondary hypotheses structural equation models will be used The secondary analyses will be conducted across several domains modeled as latent variables
Control variables The stratified randomized block design should lead to comparable groups with respect to key variables of interest namely age depression level and diabetes control at baseline To the extent that our groups are heterogeneous with respect to these variables they will be included as model covariates to reduce within group variability and increase power Gender and ethnicity may also be included in our models as dummy coded variables
Test of our Primary Hypothesis Because this project involves a longitudinal design with 2 conditions measured at multiple times we will use mixed modeling to test our primary hypothesis This approach will allow us to compare the SC and CALM-D conditions on the trajectory of change on our primary ie BDI weight HbA1c medication adherence variables Additionally the mixed model allows us to incorporate relevant covariates into our specified models See Core D for a fuller description of our modeling
In addition to mixed models we will use latent growth modeling to assess indirect paths to test potential mediators of the relationship between our conditions and outcome variables The program that will be used for these analyses is Mplus Muthen Muthen 1998 We will use hypothesis driven tests of mediation Briefly we will compare nested models one with direct and indirect paths and the second with indirect paths only but without the direct path If the difference between the models using the χ2 difference test is not significant than we dont need the direct path and this will support the hypothesis of mediation For example we will assess whether a significant CALM-D effect on decreasing depression is due to increased medication adherence In Core D we specify how we will combine data across projects for tests of mediation
Power Analyses Power calculations for the specific aims are included below All power calculations were done using the statistical software nQuery Elashoff 2000 Power is presented for a two group intervention vs control design In addition to needing to calculate the effect of our intervention on the primary endpoint we are also concerned with the need for calculating power for our mediation hypothesis which we consider to be exploratory
Because patient retention and adherence to protocol will be a major emphasis in this project we intend to use a 3 session run-in prior to randomization Patients who appear to be medically eligible meet study criteria for major depression and who express willingness to participate return for a session in which the patient completes a medical history form undergoes a brief physical exam takes a maximum exercise stress test is given a standardized dietary assessment and is taught how to use a food diary and activity monitor At the beginning of the third run-in session the patient returns the completed food diary and data from the activity monitor is recorded The patient then takes a 2 hour oral glucose tolerance test OGTT during which time he or she answers questions about health habits psychosocial functioning and health quality of life After a brief rest and snack the patient is escorted to the Ultrasound Laboratory for assessment of echocardiography carotid artery imaging and brachial artery endothelial functioning Patients who satisfactorily complete all three run-in sessions meet eligibility requirements and are interested in participating are then asked to provide informed consent and are randomized into the CALM-D or SC conditions
Randomization will be implemented using a stratified randomized block design Eight strata will be designated on the basis of age 50 vs 50 years severity of depression 24 vs 24 on the HRSD and glycemic control 8 vs HbA1c at baseline Within each stratum random sequences will be generated in blocks of sizes 2 4 or 6 The block size will also be randomly chosen In this manner the resulting sequence will look purely random but will be fairly closely balanced with respect to the critical variables of age depression and severity of diabetes Piantadosi 1997 Elements in the random sequences will be paired with the subject number of participants assigned to each stratum The number of sequences generated for each stratum will vary depending on the number of eligible participants in that stratum These sequences will be concealed until the treatment conditions are actually assigned
The SC patients will be treated in accordance with ADA Clinical Practice Guidelines 2005 which will include at least 2 HbA1c tests lipid profile test for microalbuminuria dilated retinal eye exam complete foot exam and influenza immunization each year plus prescribed aspirin therapy and a screen for readiness to stop smoking if they smoke Smokers are encouraged to stop using ADA recommendations in the Guidelines In addition each patients physician will receive after baseline 6 months and 1 year a report including OGTT insulin resistance oxidative stress inflammation lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology psychosocial functioning and health quality of life Participants in the CALM-D condition will receive all of the above but also 2 individual counseling sessions on a getting started being active losing weight and managing stress and b negative thoughts and emotions including a discussion of ways to curb emotional eating Following the 2 individual sessions there will be 2 weekly group sessions followed by 4 bi-weekly sessions and then 9 monthly sessions Each session in CALM-D will be 1 hour long and will include deep breathing relaxation 5 min homework review including medication adherence activity level and fat and caloric intake 10 min session topics and homework assignment 45 min The group topics include such issues as Wheres the FatThree Ways to Eat Less Fat and Taking Your MedicationsStress and You Although participants and interventionists will be aware of the patients treatment assignment all staff who collect verify or classify end point data or follow-up assessments will be masked as much as possible
The primary outcomes of the study will be a depression b weight and waist circumference c HbA1c and d medication adherence Secondary outcomes will include a glucose tolerance b insulin resistance c inflammation d fibrinolysis e lipid profile f oxidative stress g endothelial function h resting blood pressure i cardiac and vascular function j cardiac morphology k psychosocial functioning and l health quality of life The above variables will be assessed at baseline after 6 months and after 1 year Data will be analyzed using mixed-model analyses to determine change over time as a function of experimental condition This will be done using the PROC Mixed module of SAS software Littell Milliken Stroup Wolfinger 1996 This methodology is useful for intent to treat analyses in that it does not require complete data across multiple time points
Approximately 50 of the patients we intend to recruit are likely to be LatinoHispanic based on our previous experience most of these LatinoHispanic participants will prefer to speak write and answer questions in Spanish All of the instruments proposed are available in Spanish To a large extent the CALM-D intervention developed for the present project is based on both the DPP and ENRICHD protocols We recognize of course that language and ethnicity are not the same However there is a great deal of diversity among LatinoHispanics in the patient sample we have enrolled from the Jackson Health Care System including Cubans Colombians Puerto Ricans Nicaraguans Dominicans Mexicans Peruvians and Guatamalans among others
During the 2 hour OGTT the participant will complete questionnaires including a Medical History Form eg demographics risk factors comorbid illnesses medications b health habits eg smoking alcohol use physical activity c psychosocial functioning eg BDI DISH and d health quality of life In addition to providing measures of blood glucose and plasma insulin the blood draw will permit assessment of HbA1c inflammation fibrinolysis and lipids After the OGTT the assessor will provide the participant with a snack and allow for a brief rest period Then the RD will conduct a dietary assessment and record the data from the activity monitor The participant will then be escorted to the Ultrasound Laboratory for assessment of echocardiography carotid artery imaging and brachial artery endothelial function At the completion of the session the participant will report to the Assessors review the days events be thanked for participating and paid 100 reimbursement for his or her time and transportation
Physical measures Activity monitor Between the second and third week of the run-in Baseline and 1 week before the 6 month and 12 month assessments all participants will wear activity monitors for physical activity The participants will also complete the Blair 1984 questionnaire for the same one-week period Participants in the CALM-D condition will be reminded one week prior to each of 17 intervention sessions to wear the accelerometer daily and bring it to the next session We intend to use the New Lifestyle NL-2000 activity monitor This device weighs 25 ounce count steps and estimates calories burned The caloric estimate subtracts calories burned in maintenance and adjusts for intensity based upon steps per unit of time This device has a 7 day automatic memory that starts each midnight at zero
Albuminuria Albumin and creatinine will be measured during the 2nd run-inassessment Baseline session by urine sample see Core B Serum creatinine will also be measured Patients will be excluded if there is evidence of renal disease ie urine dipstick protein 4 serum creatinine 14 mgdL in women or 15 mgdL in men or currently receiving dialysis In those patients who meet criteria for entry into the study the incidence and progression of microalbuminuria or greater level of excretion will be assessed using an albumincreatinine ratio at both 6 month and 12 month follow-up Serum creatinine will also be measured at these times
Cardiorespiratory fitness Fitness will be evaluated at Baseline second run-inassessment session and at 6- and 12-month follow-up with a maximal treadmill test see Core C The Baseline symptom-limited maximum stress test represents the current standard of care for an exercise prescription The primary measure for assessing change will be change in maximal oxygen uptake VO2 max Heart rate ECG changes blood pressure and VO2 max will be determined during the exercise test For the maximum exercise stress tests the participant will be continued on any prescribed medication for cardiovascular disease The following 3 abnormalities classify an individual at moderate to high risk for cardiac complication during exercise and will result in study exclusion 1 2 or more previous myocardial infarctions 2 previous episode of primary cardiac arrest 3 exercise capacity 6 METS 4 ischemic horizontal or downsloping ST segment depression 40 mm or 5 angina during exercise see Core C for details
Diabetes control CALM-D will include measurement of HbA1c fasting glucose and response to oral glucose challenge at Baseline run-inassessment session 2 and at both 6- and 12-month follow-up Patients will be excluded at Baseline if HbA1c 11
Psychosocial measures Beck Depression Inventory BDI The BDI Beck 1967 taps several domains of depression Of the 21 items on the scale 11 deal with cognition 2 with affect 2 with overt behavior 1 with interpersonal symptoms and 5 with somatic symptoms In overweight type 2 diabetic patients somatic symptoms may reflect physical disease processes eg fatigue or inflammation rather than primary depression For this reason subanalyses separating out effects of the intervention on somatic vs nonsomatic items will be important The BDI has been used extensively in English Spanish and various European speaking populations with internal reliability between α 85-93 eg Sanz Vázquez 1993
Perceived Stress Scale PSS The PSS Cohen S Williamson G 1988 is a 10 item scale that measures the degree to which situations in peoples lives are perceived as stressful unpredictable uncontrollable overwhelming and has good reliability α 85
Cook-Medley Hostility Scale Ho The Ho scale Cook Medley 1954 is composed of 50 true-false items taken from the MMPI that measures cynicism and mistrust of others and has adequate test -retest reliability internal consistency and construct validity Smith 1992 It has been shown in a number of large scale prospective studies to be associated with increased risk for CHD Miller et al 1996
Coping The Brief Cope Carver 1997 will be used to assess coping strategies that may be moderating CALM-D intervention effects This instrument has demonstrated high internal consistency adequate stability over time and substantial convergent validity Based on our previous studies using the Cope we shall be looking at the following 2 item subscales 1 active coping 2 using emotional support 3 using instrumental support and 4 behavioral disengagement Subscales 1 2 and 3 will also be used as a composite measure
Perceived Social Support Scale PSSS The PSSS Blumenthal et al 1987 is a 12-item scale that addresses perceived support from family friends and significant others It has established reliability and is related to CHD
Health quality of life Health Status Questionnaire Short Form SF-36 The SF-36 Ware Sherbourne 1992 is a 36-item instrument with 8 multi-item scales 1 physical functioning 2 social functioning 3 role limitations due to physical health problems 4 role limitations due to personal or emotional problems 5 general mental health 6 vitality 7 bodily pain and 8 general health perceptions Subscale reliabilities have been above 08 in multiple population studies conducted on adults It has successfully been used to evaluate functional status in depressed chronically ill and healthy individuals Wells et al 1989
Intervention In the present project all participants a will meet diagnostic criteria for major depressive disorder unless currently prescribed an antidepressant medication and have both a prior diagnosis of depression and current BDI score 11 It should be noted that a patient with type 2 diabetes has approximately the same risk of an MI as a patient who has already had an MI but does not have diabetes Haffner et al 1998
During the study half of the participants all of whom are depressed will be randomized to the CALM-D intervention and half into standard care
The CALM-D intervention consists of 17 sessions The first 4 sessions meet weekly Sessions 1 and 2 are individual sessions in which counselor and participant get to know one another and build rapport They also provide the participant with the opportunity to ask questions describe potential barriers and express reservations Sessions 3 and 4 which also meet weekly encourage participants to get to know one another and deal with issues concerning diet and medication adherence After the first 4 weekly sessions participants meet for 4 biweekly sessions followed by 9 monthly sessions One week prior to each bi-weekly and monthly session the therapist will call to remind the participant of the next meeting and request that the participant wear the accelerometer and fill-out the food diary daily until the upcoming session Immediately prior to each CALM-D intervention session the participant is weighed accelerometer results are recorded and the food diary is turned in Upon initial randomization into the intervention condition and again during session 1 the participant is told that he or she is invited to ask a partner family member living in the household or a friend to come to the intervention sessions The topic for each session are shown in Table D39
Table D29 Session Topic Weekly
1 I Welcome to the CALM-D Program Getting Started Being Active Losing Weight and Managing Stress
2 I Negative Thoughts and Emotions
3 G Wheres the FatThree Ways to Eat Less Fat
4 G Taking Your MedicationsStress and You Bi weekly
5 G Move Those MusclesBeing Active A Way of Life
6 G Challenging and Changing Negative Thoughts
7 G Healthy Eating
8 G Problem Solving Monthly
9 G Four Keys to Healthy Eating Out
10 G Social SupportCommunication
11 G Take Charge of Whats Around YouTip the Calorie Balance
12 G The Slippery Slope of Lifestyle Change
13 G Jump Start Your Activity Plan
14 G AssertivenessMake Social Cues Work for You
15 G You Can Manage Stress
16 G Life Goals
17 G Ways to Stay Motivated Abbreviations I Individual session G Group session
The objectives of the intervention are for participants to a lose 7 of their weight through healthy eating b do 25 hrs of brisk physical activity each wk eg walk briskly for 30 min 5x per week c manage stress better eg through coping strategies deep breathing and d always take their medication Participants are also taught how to fill out a food diary
At the outset of the intervention the counselor will discuss the effects of excess weight on diabetes and how complications of diabetes can be decreased with improved diet and increased activity level In terms of diet participants are taught how to use a fat counter and read labels weigh and measure foods eat less fat change eating habits to better match the food pyramid choose healthy eating behaviors make healthy food choices when eating out and relate calorie balance to weight loss To promote physical activity participants discuss current activity level benefits of being more active possible activities that can be undertaken regularly how to overcome barriers to activity and ways to prevent injury The participants also learn how to use an accelerometer Later in the program patients learn the definition of aerobic fitness and its relationship to frequency intensity time and type of activity Ways to add interest and variety to activity plans are also discussed
As a precursor to learning how to manage stress participants are taught how to identify types of negative thinking and the relationships among thoughts emotions and ways to curb emotional eating The counselor also stimulates discussion on how failure to take prescribed antidepressants can lead to mood related physical inactivity and other unhealthy health behaviors eg excessive alcohol use overeating Participants are taught how to assess if negative thoughts are accurate replace inaccurate negative thoughts with accurate thoughts handle situations in which one cant fix the problem identify sources of emotional and tangible support and use them effectively prevent stress and cope with stress The intervention also deals with the need for handling lapses and relapses regarding diet physical activity depression and medication adherence Participants are taught to identify high-risk situations and early warning signs as well as how to use adaptive coping strategies
Specific strategies to achieve the weight loss goal A weight loss goal of 7 is set which should lead to a loss of 7-21 lbs within 24 weeks Participants will be weighed in private at each session and this will be recorded on the weight graph in each participants notebook Participants will be encouraged if possible to weigh themselves outside of the study venues A total fat intake goal will be set based upon 25 total calories from fat A total caloric intake goal will also be set Daily self-monitoring of food intake fat and calories will be requested of participants with food measuring tools and a fat and calorie counter will be provided A more simplified form of self-monitoring will be provided for participants with very limited reading and math skills
Specific strategies to achieve the physical activity goal A physical activity goal of 700 kilocalories per week or 25 hours of moderate activity is set in a step-wise fashion to be reached in 5-weeks Another goal is to reach 10000 steps per week recorded on the accelerometer Participants will be asked to maintain daily physical activity records in their diaries based on information from the accelerometer Sites at which physical activity can be safely and effectively undertaken will be identified for each participant based on their residence
Specific strategies to achieve the medication adherence goals Participants list all of the medications they take and keep this list in a notebook The purpose of each medication is explained to the participant as well as the reasons for always taking the medication each day as prescribed Participants are encouraged to develop the habit of taking their medications as prescribed at the same time each day Discussions about handling weekends going on vacation etc are discussed during intervention sessions Reminders about taking medications are offered at each session and each phone call Refills of medications are carefully tracked When participants report that they are running low on a medication they are encouraged to obtain refills promptly Reported side effects of medications are carefully monitored and attempts made to determine if the side effects are easily remedied eg take just before bedtime take with breakfast or are due to not following instructions correctly If necessary the participant is referred to his or her physician for consideration of a change in medication
Counselors and their supervision The counselors we propose to use in this intervention are licensed PhD Clinical psychologists who have served as counselors in the post-MI project and in the adolescent intervention project of the present program project Supervision is carried out by Dr Patrice Saab PhD who helped to develop both of our intervention protocols and received supervisory training from the Beck Institute in conjunction with the ENRICHD trial and by Dr Ronald Goldberg MD who was the PI of the Miami site for the DPP Based on weekly reviews of audiotaped sessions Dr Saab will determine using a protocol check list intervention adherence to the manual point out any drift or lack of fidelity to the protocol and offer professional suggestions on how to remediate problems Using standards developed in DPP Dr Goldberg will assure that counselors are adhering to protocol with regard to such issues as using a fat counter weighing and measuring foods using the food pyramid and supervising exercise and food diary homework Weekly supervision is an institutionalized component of all of our intervention programs
Study hypotheses related to Primary aims and their association In accordance with the specific aims it is hypothesized that
From Primary Aim 1 Participants enrolled in the CALM-D intervention will show significantly greater improvement in BDI depression scores compared to participants in the SC condition
The greater improvement in BDI score in the CALM-D than in the SC condition will be mediated by increased medication adherence and improved coping skills by CALM-D participants
From Primary Aim 2 Participants enrolled in the CALM-D intervention will show significantly greater weight loss than participants in the SC condition
The greater weight loss in the CALM-D than in the SC condition will be mediated by decreased depression increased adherence to dietary instructions and increased physical activity
From Primary Aim 3 Participants enrolled in the CALM-D intervention will show significantly lower HbA1c in the SC condition
The greater decrease in HbA1c in the CALM-D than in the SC condition will be mediated by greater weight loss improved nutrition and increased exercise
From Primary Aim 4 Participants enrolled in the CALM-D intervention will show significantly greater medication adherence than participants in the SC condition
The greater increase in anti-depressant medication adherence in the CALM-D than in the SC condition will be mediated by improved coping skills and an increase in perceived social support
The greater increase in adherence to prescribed medications other than anti-depressants in the CALM-D than in the SC condition will be mediated by decreased depression and improved coping skills
Study hypotheses related to secondary aims In accordance with the studys secondary aims it is hypothesized that
Participants enrolled in the CALM-D intervention will show significantly improved insulin sensitivity and tolerance to oral glucose challenge compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved procoagulation and endothelial function and decreased inflammation and oxidative stress compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved lipid profiles compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show lower resting blood pressure and improved cardiac and vascular function as well as cardiac morphology compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved psychosocial functioning compared to participants in the SC condition
Participants enrolled in the CALM-D intervention will show improved health quality of life compared to participants in the SC condition
The greater improvement in improved tolerance to oral glucose challenge insulin sensitivity procoagulation oxidative stress lipid profile endothelial function resting blood pressure cardiac and vascular function cardiac morphology and health quality of life will each be associated with decreased waist circumference
Statistical analyses Preliminary analyses All data will be inspected employing quality control procedures Descriptive statistics will be computed for every study variable to ensure that all data values are within expected ranges and to eliminate any data errors that may have occurred If needed in the event that some of our variables are not normally distributed we will transform these variables using log transformations or use non-parametric statistics A mixed model analysis program using SAS Proc Mixed for growth models will be used to assess our 4 primary hypotheses Missing data will be handled using the full information likelihood algorithm which uses all the data available for all participants To assess our secondary hypotheses structural equation models will be used The secondary analyses will be conducted across several domains modeled as latent variables
Control variables The stratified randomized block design should lead to comparable groups with respect to key variables of interest namely age depression level and diabetes control at baseline To the extent that our groups are heterogeneous with respect to these variables they will be included as model covariates to reduce within group variability and increase power Gender and ethnicity may also be included in our models as dummy coded variables
Test of our Primary Hypothesis Because this project involves a longitudinal design with 2 conditions measured at multiple times we will use mixed modeling to test our primary hypothesis This approach will allow us to compare the SC and CALM-D conditions on the trajectory of change on our primary ie BDI weight HbA1c medication adherence variables Additionally the mixed model allows us to incorporate relevant covariates into our specified models See Core D for a fuller description of our modeling
In addition to mixed models we will use latent growth modeling to assess indirect paths to test potential mediators of the relationship between our conditions and outcome variables The program that will be used for these analyses is Mplus Muthen Muthen 1998 We will use hypothesis driven tests of mediation Briefly we will compare nested models one with direct and indirect paths and the second with indirect paths only but without the direct path If the difference between the models using the χ2 difference test is not significant than we dont need the direct path and this will support the hypothesis of mediation For example we will assess whether a significant CALM-D effect on decreasing depression is due to increased medication adherence In Core D we specify how we will combine data across projects for tests of mediation
Power Analyses Power calculations for the specific aims are included below All power calculations were done using the statistical software nQuery Elashoff 2000 Power is presented for a two group intervention vs control design In addition to needing to calculate the effect of our intervention on the primary endpoint we are also concerned with the need for calculating power for our mediation hypothesis which we consider to be exploratory
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None