Ignite Creation Date:
2024-05-06 @ 3:03 AM
Last Modification Date:
2024-10-26 @ 11:27 AM
Study NCT ID:
NCT02190097
Status:
COMPLETED
Last Update Posted:
2022-12-01
First Post:
2014-06-20
Brief Title:
Paleo Versus Healthy ADA Diets for Treatment of Polycystic Ovarian Syndrome PCOS
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
PALEOLITHIC VS Healthy ADA DIETS FOR TREATMENT OF POLYCYSTIC OVARIAN SYNDROME PCOS
Status:
COMPLETED
Status Verified Date:
2022-11
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:
None
Brief Summary:
Polycystic ovary syndrome PCOS is a syndrome which includes elevated androgen levels irregular menstrual cycles and insulin resistance Standard treatments which include weight loss and medications to improve insulin secretion are only partly successful and may require that young women take medications for decades
The study investigators have been evaluating the effects of specific diets on insulin resistance in healthy volunteers and subjects with type 2 diabetes and have found that subjects with insulin resistance seem to respond particularly well to these diet regimens
Volunteers with PCOS are being asked to participate to see if following these diets can help regularize your menstrual cycles The results of this study may help improve fertility treatments for women with PCOS
The study investigators have been evaluating the effects of specific diets on insulin resistance in healthy volunteers and subjects with type 2 diabetes and have found that subjects with insulin resistance seem to respond particularly well to these diet regimens
Volunteers with PCOS are being asked to participate to see if following these diets can help regularize your menstrual cycles The results of this study may help improve fertility treatments for women with PCOS
Detailed Description:
Experimental Design and Methods This is a prospective open labeled randomized diet intervention study done on adult participants with PCOS After signing informed consents participants will be asked to eat a recommended ADA diet for two weeks run in period Participants will then have baseline testing including urine and blood tests to evaluate insulin resistance fasting glucose and insulin 2 hour oral glucose tolerance test electrolytes to assess acid-base status ovarian volume and testosterone levels measured to assess severity of PCOS and questionnaires about menstrual frequency eating habits and stress Participants will then be randomized to either a high fruits and vegetable Paleo Diet for 4-8 months or a standard ADA-recommended diet for the first 4 months followed by Paleo Diet for 0-4 monthsAll participants will have the option of limiting their participation to just 4 months or extending participation to the full 8 months depending on their ongoing level of interest All testing will be repeated at 4 months crossover point and at completion of the diets at 8 months The primary outcome variables are menstrual cycle frequency and ovarian volume and secondary outcomes include metabolic profiles and eatingbehavior questionnaires
Procedures
1 Diet All participants will initially be given diet information on ADA diet for the Run In period including printed ADA diet instructions and advice on caloric intake The ADA diet includes foods that are excluded in the Paleo Diet such as grains legumes and dairy products and will also contain less potassium All participants will be instructed not to add salt to their food when cooking or eating At 2 weeks participants will be randomized to Paleo Diet arm or ADA diet arm Participants on the Paleo Diet arm will require a ramp-up phase for one week start out with 1 Paleo meal per day then two and then all meals will be on a Paleolithic-type menu which contains approximately an average of 142 grams of protein and 12200 mg of potassium per 3000 kcal Participants on the ADA diet arm will continue on the run-in diet
After 16 weeks the participants in the ADA arm will be changed over to the Paleo arm if they wish to continue participation They will also require a ramp-up phase for 1 week In our previous studies we have seen a crossover effect at one month going from the Paleo to the ADA diet but not from the ADA to the Paleo arm
We will give all participants pertinent websites and written information about their specific diet as well as sample menus We will give participants in the Paleo arm a list of foods to avoid eg dairy grains legumes processed foods
The main obstacles to compliance with outpatient diets include the cost the amount of time needed and ignorance about where to get specific kinds of foods We will give them lists of various supermarkets and farmers markets times and dates we will advise participants about making up batches of foods on the weekends and freezing them and if they have families or other support we will try to get them involved in support
2 Monitoring dietary compliance We will monitor compliance in a number of ways
We have recruited four nutrition student volunteers from UC Berkeley who will work closely with the participants to help them adapt the study diets to their everyday living situations The nutrition students will help design the materials we will give the participants as well as give dietary advice We are working on a number of electronic and social media methods for keeping track of what our subjects are eating These include
Initially daily or near daily contacts for the first week of each diet then at least weekly contacts and then at least monthly contacts
online data system that monitors food and activity eg the USDA super tracker myfitnesspal etc
tweets or texts that ask the subjects to go to an elink and answer a few questions eg did you eat grains today The answers are downloaded to a database that can be compiled to reflect dietary compliance for each subject
We will also develop a secure website so that participants from each group can discuss with others what problems and solutions they are using
Last we will also assess 24 hour urines for creatinine sodium and potassium at 0 16 and 32 weeks Both of these diets will be higher in potassium and lower in sodium than typical American diets Although we expect our subjects will be motivated enough to follow these diets from our previous studies we have found that some subjects were not honest about what they were eating and this was reflected in the 24 hour urine excretion of potassium and sodium
Assays
Samples will be drawn at time 0 week 8 week 16 week 24 and week 32 We will collect serum plasma and urine at all these timepoints for banking The following tests will be performed at time table 2
1 CBC Chemical profile blood lipids cardiovascular risk factors and inflammatory cytokines and adipokines time 0 week 16 week 32 Electrolytes liver function tests fasting glucose lipid panel and insulin levels will be measured by Quest labs PAI-1 will be measured by a colorimetric assay Chemicon Temecula CA Homocysteine fibrinogen hsCRP and ICAM-1 will be assayed by the UCSF clinical laboratory using standard analytical methods Commercial kits will be used to measure fasting serum non-esterified fatty acids Wako Diagnostics kit Richmond Virginia serum TNF-α IL-6 adiponectin and leptin Quantikine HS high sensitivity ELISA R D Systems Minneapolis MN
2 Systemic oxidative stress time 0 weeks 16 32 we will measure 4 serum markers of oxidative stress protein carbonyls a product of protein oxidation TBARS a measurement of lipid peroxidation TRAP a measure of total antioxidant activity and isoprostanes formed from the peroxidation of arachidonic acid in lipoproteins and membranes Blood samples will be drawn in the fasted state both at initial screening and after ALA treatment Protein carbonyls TBARS and TRAP will be performed at UC Davis Clinical Laboratories employing standard techniques Serum 8-isoprostane-F2α will be measured by KRONOS Science laboratory Phoenix Arizona We will also measure urine markers of oxidative stress before and after CRLA treatment These will include 8-isoprostane-F2α and 8-hydroxy guanosine a marker of oxidized DNA These urine assays will be performed KRONOS Science laboratory Phoenix Arizona and Dr Jack Roberts Vanderbilt University
3 Telomere assessment The length of telomeres the DNA caps at the ends of chromosomes is emerging as an indicator of stress-related biological aging Data have implicated accelerated telomere shortening in the context of increased psychological stress and stress arousal 10 11Blood drawn by a licensed phlebotomist 4 mL for telomere assessment at baseline 0 weeks and 16-weeks will be assayed for telomere length Samples will be frozen and transferred on dry ice to the Blackburn Laboratory at UCSF located at 600 16th Street San Francisco California by a laboratory technician Assays will be completed according to the polymerase chain reaction PCR method
4 24 hr urine collections collections as per clinical protocol We will measure volume Na K pH creatinine and calcium
Reproductive testing
Subjects will undergo assessment of 1SHBG and androgen levels total testosterone androstenedione and DHEAS 2 clinical hyperandrogenism hirsutism by modified Ferriman-Gallwey and acne scores 3 menstrual cyclicity cycle interval and pattern and 4 ovarian morphology follicle count and ovarian volume
Androgen levels times 0 weeks 16 32 Two serum samples will be obtained 30 minutes apart Serum will be isolated and aliquoted for future analysis of androstenedione A testosterone T DHEAS 17 hydroxyprogesterone 17-OHP and SHBG
Clinical hyperandrogenism The presence and extent of hirsutism will be determined using a modification of the Ferriman-Gallwey FG scoring method12 while acne will be scored according to the American Academy of Dermatology Subjects will be requested to avoid any mechanical treatment for hair removal for 4 weeks prior to the baseline visit and to list all such treatments that are utilized during the study and their frequency
Menstrual cyclicity Menstrual frequency will be assessed as a menstrual frequency ratio as described by Elkind-Hirsch 13so that menstrual events are normalized to the normal interval of 12 menses per year MFR10 or for instance those with 6 cycles per year would have an MFR of 05
Ovarian morphology All subjects will undergo a transvaginal ultrasound TVUS to obtain an antral follicle count at baseline 8 and 16 weeks The study investigator will image both the left and right adnexal areas in two planes and make measurements of the transverse longitudinal and anteroposterior diameters of each ovary using electronic calipers on a Shimadzu SDU-450XL machine with a variable 4-8 mHz vaginal transducer The examination of each adnexa will ensure an adequate opportunity to locate the organs Inability to locate adnexa in this age group is less than 1 internal data All echo-free structures in the ovaries will be regarded as follicles Follicles with a mean diameter of two dimensions between 2 and 10 mm will be counted Calculation of all follicles 2-10mm as well as those 2- 5mm will be possible as these numbers will be recorded separately The total between the two ovaries 2- 10mm will be considered the AFC The volume of each ovary will be calculated by measuring the three perpendicular diameters and applying the formula for an ellipsoid L x H x W x π6 Data will be entered directly onto scannable datasheets Examination will also determine whether cystsother abnormalities exist and provide images to document number and type of abnormalities Clinical alerts will be generated for ovarian cysts of greater than 3cm diameter or solid adnexal masses of any size Dr Huddleston will be responsible for relaying information about clinical alerts to patients and physicians
5 Body composition Total body water TBW and extracellular water ECW volumes will be determined by bioimpedance spectroscopy Intermed Inc Melbourne Australia at baseline 16 and 32 weeks Subjects will also be weighed at each visit We will also do waist and hip measurements at baseline 16 and 32 weeks
6 Blood pressure BP and heart rate HR These will be measured at each visit in the morning after 10 minutes of rest in the sitting position using an automated oscillometric device Dinamap Critikon Inc programmed to obtain 3 readings within 3 minutes and then will calculate average daily pressure
j Questionnaires Participants will complete the following questionnaires per the schedule specified in Table 1 Questionnaires tap psychological experience health and eating behavior and adherence
Procedures
1 Diet All participants will initially be given diet information on ADA diet for the Run In period including printed ADA diet instructions and advice on caloric intake The ADA diet includes foods that are excluded in the Paleo Diet such as grains legumes and dairy products and will also contain less potassium All participants will be instructed not to add salt to their food when cooking or eating At 2 weeks participants will be randomized to Paleo Diet arm or ADA diet arm Participants on the Paleo Diet arm will require a ramp-up phase for one week start out with 1 Paleo meal per day then two and then all meals will be on a Paleolithic-type menu which contains approximately an average of 142 grams of protein and 12200 mg of potassium per 3000 kcal Participants on the ADA diet arm will continue on the run-in diet
After 16 weeks the participants in the ADA arm will be changed over to the Paleo arm if they wish to continue participation They will also require a ramp-up phase for 1 week In our previous studies we have seen a crossover effect at one month going from the Paleo to the ADA diet but not from the ADA to the Paleo arm
We will give all participants pertinent websites and written information about their specific diet as well as sample menus We will give participants in the Paleo arm a list of foods to avoid eg dairy grains legumes processed foods
The main obstacles to compliance with outpatient diets include the cost the amount of time needed and ignorance about where to get specific kinds of foods We will give them lists of various supermarkets and farmers markets times and dates we will advise participants about making up batches of foods on the weekends and freezing them and if they have families or other support we will try to get them involved in support
2 Monitoring dietary compliance We will monitor compliance in a number of ways
We have recruited four nutrition student volunteers from UC Berkeley who will work closely with the participants to help them adapt the study diets to their everyday living situations The nutrition students will help design the materials we will give the participants as well as give dietary advice We are working on a number of electronic and social media methods for keeping track of what our subjects are eating These include
Initially daily or near daily contacts for the first week of each diet then at least weekly contacts and then at least monthly contacts
online data system that monitors food and activity eg the USDA super tracker myfitnesspal etc
tweets or texts that ask the subjects to go to an elink and answer a few questions eg did you eat grains today The answers are downloaded to a database that can be compiled to reflect dietary compliance for each subject
We will also develop a secure website so that participants from each group can discuss with others what problems and solutions they are using
Last we will also assess 24 hour urines for creatinine sodium and potassium at 0 16 and 32 weeks Both of these diets will be higher in potassium and lower in sodium than typical American diets Although we expect our subjects will be motivated enough to follow these diets from our previous studies we have found that some subjects were not honest about what they were eating and this was reflected in the 24 hour urine excretion of potassium and sodium
Assays
Samples will be drawn at time 0 week 8 week 16 week 24 and week 32 We will collect serum plasma and urine at all these timepoints for banking The following tests will be performed at time table 2
1 CBC Chemical profile blood lipids cardiovascular risk factors and inflammatory cytokines and adipokines time 0 week 16 week 32 Electrolytes liver function tests fasting glucose lipid panel and insulin levels will be measured by Quest labs PAI-1 will be measured by a colorimetric assay Chemicon Temecula CA Homocysteine fibrinogen hsCRP and ICAM-1 will be assayed by the UCSF clinical laboratory using standard analytical methods Commercial kits will be used to measure fasting serum non-esterified fatty acids Wako Diagnostics kit Richmond Virginia serum TNF-α IL-6 adiponectin and leptin Quantikine HS high sensitivity ELISA R D Systems Minneapolis MN
2 Systemic oxidative stress time 0 weeks 16 32 we will measure 4 serum markers of oxidative stress protein carbonyls a product of protein oxidation TBARS a measurement of lipid peroxidation TRAP a measure of total antioxidant activity and isoprostanes formed from the peroxidation of arachidonic acid in lipoproteins and membranes Blood samples will be drawn in the fasted state both at initial screening and after ALA treatment Protein carbonyls TBARS and TRAP will be performed at UC Davis Clinical Laboratories employing standard techniques Serum 8-isoprostane-F2α will be measured by KRONOS Science laboratory Phoenix Arizona We will also measure urine markers of oxidative stress before and after CRLA treatment These will include 8-isoprostane-F2α and 8-hydroxy guanosine a marker of oxidized DNA These urine assays will be performed KRONOS Science laboratory Phoenix Arizona and Dr Jack Roberts Vanderbilt University
3 Telomere assessment The length of telomeres the DNA caps at the ends of chromosomes is emerging as an indicator of stress-related biological aging Data have implicated accelerated telomere shortening in the context of increased psychological stress and stress arousal 10 11Blood drawn by a licensed phlebotomist 4 mL for telomere assessment at baseline 0 weeks and 16-weeks will be assayed for telomere length Samples will be frozen and transferred on dry ice to the Blackburn Laboratory at UCSF located at 600 16th Street San Francisco California by a laboratory technician Assays will be completed according to the polymerase chain reaction PCR method
4 24 hr urine collections collections as per clinical protocol We will measure volume Na K pH creatinine and calcium
Reproductive testing
Subjects will undergo assessment of 1SHBG and androgen levels total testosterone androstenedione and DHEAS 2 clinical hyperandrogenism hirsutism by modified Ferriman-Gallwey and acne scores 3 menstrual cyclicity cycle interval and pattern and 4 ovarian morphology follicle count and ovarian volume
Androgen levels times 0 weeks 16 32 Two serum samples will be obtained 30 minutes apart Serum will be isolated and aliquoted for future analysis of androstenedione A testosterone T DHEAS 17 hydroxyprogesterone 17-OHP and SHBG
Clinical hyperandrogenism The presence and extent of hirsutism will be determined using a modification of the Ferriman-Gallwey FG scoring method12 while acne will be scored according to the American Academy of Dermatology Subjects will be requested to avoid any mechanical treatment for hair removal for 4 weeks prior to the baseline visit and to list all such treatments that are utilized during the study and their frequency
Menstrual cyclicity Menstrual frequency will be assessed as a menstrual frequency ratio as described by Elkind-Hirsch 13so that menstrual events are normalized to the normal interval of 12 menses per year MFR10 or for instance those with 6 cycles per year would have an MFR of 05
Ovarian morphology All subjects will undergo a transvaginal ultrasound TVUS to obtain an antral follicle count at baseline 8 and 16 weeks The study investigator will image both the left and right adnexal areas in two planes and make measurements of the transverse longitudinal and anteroposterior diameters of each ovary using electronic calipers on a Shimadzu SDU-450XL machine with a variable 4-8 mHz vaginal transducer The examination of each adnexa will ensure an adequate opportunity to locate the organs Inability to locate adnexa in this age group is less than 1 internal data All echo-free structures in the ovaries will be regarded as follicles Follicles with a mean diameter of two dimensions between 2 and 10 mm will be counted Calculation of all follicles 2-10mm as well as those 2- 5mm will be possible as these numbers will be recorded separately The total between the two ovaries 2- 10mm will be considered the AFC The volume of each ovary will be calculated by measuring the three perpendicular diameters and applying the formula for an ellipsoid L x H x W x π6 Data will be entered directly onto scannable datasheets Examination will also determine whether cystsother abnormalities exist and provide images to document number and type of abnormalities Clinical alerts will be generated for ovarian cysts of greater than 3cm diameter or solid adnexal masses of any size Dr Huddleston will be responsible for relaying information about clinical alerts to patients and physicians
5 Body composition Total body water TBW and extracellular water ECW volumes will be determined by bioimpedance spectroscopy Intermed Inc Melbourne Australia at baseline 16 and 32 weeks Subjects will also be weighed at each visit We will also do waist and hip measurements at baseline 16 and 32 weeks
6 Blood pressure BP and heart rate HR These will be measured at each visit in the morning after 10 minutes of rest in the sitting position using an automated oscillometric device Dinamap Critikon Inc programmed to obtain 3 readings within 3 minutes and then will calculate average daily pressure
j Questionnaires Participants will complete the following questionnaires per the schedule specified in Table 1 Questionnaires tap psychological experience health and eating behavior and adherence
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