Ignite Creation Date:
2024-05-05 @ 11:20 PM
Last Modification Date:
2024-10-26 @ 10:32 AM
Study NCT ID:
NCT01305889
Status:
COMPLETED
Last Update Posted:
2022-05-26
First Post:
2011-02-25
Brief Title:
The Effect of Problem Solving Therapy and Antidepressant Therapy on Cerebral Perfusion and Brain Derived Neurotropic Factor BDNF in Depressed Elders
Sponsor:
University of California San Francisco
Organization:
University of California San Francisco
Study Overview
Official Title:
The Effect of Problem Solving Therapy and Antidepressant Therapy on Cerebral Perfusion and Brain Derived Neurotropic Factor in Depressed Elders
Status:
COMPLETED
Status Verified Date:
2022-05
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:
The focus of this study is to gather preliminary data regarding the effects of a psychological therapy-Problem Solving Therapy-and an antidepressant medication-sertraline-on 1 cerebral perfusion CP 2 brain derived neurotrophic factor BDNF and 3 measures of cognitive function in subjects with late life major depression LLMD This research goal will be achieved by recruiting 38 individuals over the age of 65 with LLMD The primary outcomes will be change in CP change in BDNF and change in cognitive measures from baseline to the end of 12 weeks of either therapy We will also examine predictors of treatment outcome including severity of executive dysfunction baseline BDNF concentrations and baseline CP measures The baseline neuropsychological testing brain imaging and depression assessment will be obtained in a companion study PI S Mackin CHR H42689-32681-01 that is IRB approved and is already in progress In the current study a baseline serum BDNF level will be added to Dr Mackins protocol Patients will then receive either 12 weeks of Problem Solving Therapy or antidepressant treatment with sertraline Both treatments are evidence based and commonly administered in our clinic Outcome variables will be measures of depression severity the BDNF serum concentration cerebral perfusion using a MRI arterial spin labeling ASL technique and cognitive changes in memory and executive dysfunction This is a preliminary or pilot study The primary objectives are to determine if the methods appear feasible and to determine if change in BDNF or CP occur after treatment and secondarily to determine if there are changes in cognitive functioning The study is not powered to show differences between treatments The hypotheses are 1 PST will result in increased perfusion in frontal regions of the brain but that frontal perfusion will not change with sertraline 2sertraline will result in an increase in BDNF but PST will not Change in cognitive measures of memory learning and executive dysfunction will be examined on an exploratory basis
Detailed Description:
Subjects subjects will have non-psychotic unipolar major depression based on DSM IV criteria Structured Clinical Interview for DSM IV SCIDand be 65 years or older and will have depression of moderate or greater depression severity Hamilton Depression Rating Scale score or 19 Depression severity will be assessed with the clinician rated Hamilton Depression Rating Scale HDRS and the subject rated Quick Inventory of Depressive Symptoms QIDS Ratings will be performed weekly for the first month and then every 2 weeks until the end of the trial
Neuroimaging The MRI studies included in this protocol are commonly utilized in clinical practice In addition to conventional structural MRI this protocol will utilize techniques developed to evaluate cerebral blood flow arterial spin labeling white matter integrity diffusion tensor imaging and brain biochemistry MR spectroscopy and will be performed using a 4 Tesla magnet Imaging will be performed at the VAMCUCSF Center for Imaging of Neurodegenerative Disease CIND under the direction of Michael Weiner MD Brain derived neurotropic factor BDNF a blood sample will be drawn pretreatment to determine the serum concentration of BDNF This test will be repeated post-treatment The assay for BDNF will be performed in the laboratory of Synthia Mellon PhD at UCSF Serum will be assayed for BDNF in duplicate using a commercial BDNF ELISA assay kit RD Systems Minneapolis MN USA
Cognition will be assessed with a battery of neuropsychological tests including the Stroop Color-Word Test the Trail Making Test A and B Dementia Rating Scale IP Boston Naming Test and the Hopkins Verbal Learning Test-Short
Treatment assignment If patients have a preference for PST or sertraline they will receive that treatment If they have no preference they will be randomized to one or the other until 19 subjects have been assigned to each treatment
Sertraline a selective serotonin reuptake inhibitor SSRI will be administered as the antidepressant It will be started at 25 mgday for one week and then increased to 50 mg and continued for 3 weeks At the end of 4 weeks if the patient has had limited response the dose will be increased to 100 mgday At 8 weeks if response is limited dose will be increased to 150 mgday At any time the dose can be lowered for tolerability reasons
Problem Solving Therapy Patients receiving PST will be seen weekly for 12 individual 45 minute sessions Problem Solving Therapy Arean Raue and Julian UCSF unpublished manuscript 2003 consists of 12 weekly sessions to teach participants a five-step problem-solving model This model is taught over the first five weeks of treatment Subsequent sessions are dedicated to refining PST skills In the last two PST sessions participants create a relapse prevention plan using the PST model There will be two therapists in the study both trained to perform PST and with experience in prior studies of PST for MDD in older adults
Data will be analyzed by Drs Nelson and Mackin in consultation with Kevin Delucchi PhDDepartment of BiostatisticsPsychiatry UCSF All analyses will be performed within treatment groups psychotherapy or drug treatment and will compare baseline values with post-treatment values in patients completing at least 8 weeks of treatment All analyses will begin by graphically and numerically summarizing all measures to assess the distribution of scores To statistically control for appropriate associations of other demographic variables such as age sex and education and clinical variables such as social support medical comorbidity physical frailty and medication use with the outcome measure we will use linear regression modeling methods Missing data if any will be carefully described and analyzed The methodology to be used assuming missing at random MAR which is a reasonable assumption for this type of data and the relatively low levels of missing data we anticipate based on prior research with this population Because we have specific a priori hypotheses regarding BDNF and the composite score for executive dysfunction we will not correct for multiple comparisons Analysis of the cerebral blood flow data however will employ corrections for multiple comparisons As stated the aim of the study is to gather preliminary data regarding change from baseline to the study endpoint within the sertraline or within the PST treatment group Attrition is estimated at 20 allowing for 15 patients to complete each treatment arm
Neuroimaging The MRI studies included in this protocol are commonly utilized in clinical practice In addition to conventional structural MRI this protocol will utilize techniques developed to evaluate cerebral blood flow arterial spin labeling white matter integrity diffusion tensor imaging and brain biochemistry MR spectroscopy and will be performed using a 4 Tesla magnet Imaging will be performed at the VAMCUCSF Center for Imaging of Neurodegenerative Disease CIND under the direction of Michael Weiner MD Brain derived neurotropic factor BDNF a blood sample will be drawn pretreatment to determine the serum concentration of BDNF This test will be repeated post-treatment The assay for BDNF will be performed in the laboratory of Synthia Mellon PhD at UCSF Serum will be assayed for BDNF in duplicate using a commercial BDNF ELISA assay kit RD Systems Minneapolis MN USA
Cognition will be assessed with a battery of neuropsychological tests including the Stroop Color-Word Test the Trail Making Test A and B Dementia Rating Scale IP Boston Naming Test and the Hopkins Verbal Learning Test-Short
Treatment assignment If patients have a preference for PST or sertraline they will receive that treatment If they have no preference they will be randomized to one or the other until 19 subjects have been assigned to each treatment
Sertraline a selective serotonin reuptake inhibitor SSRI will be administered as the antidepressant It will be started at 25 mgday for one week and then increased to 50 mg and continued for 3 weeks At the end of 4 weeks if the patient has had limited response the dose will be increased to 100 mgday At 8 weeks if response is limited dose will be increased to 150 mgday At any time the dose can be lowered for tolerability reasons
Problem Solving Therapy Patients receiving PST will be seen weekly for 12 individual 45 minute sessions Problem Solving Therapy Arean Raue and Julian UCSF unpublished manuscript 2003 consists of 12 weekly sessions to teach participants a five-step problem-solving model This model is taught over the first five weeks of treatment Subsequent sessions are dedicated to refining PST skills In the last two PST sessions participants create a relapse prevention plan using the PST model There will be two therapists in the study both trained to perform PST and with experience in prior studies of PST for MDD in older adults
Data will be analyzed by Drs Nelson and Mackin in consultation with Kevin Delucchi PhDDepartment of BiostatisticsPsychiatry UCSF All analyses will be performed within treatment groups psychotherapy or drug treatment and will compare baseline values with post-treatment values in patients completing at least 8 weeks of treatment All analyses will begin by graphically and numerically summarizing all measures to assess the distribution of scores To statistically control for appropriate associations of other demographic variables such as age sex and education and clinical variables such as social support medical comorbidity physical frailty and medication use with the outcome measure we will use linear regression modeling methods Missing data if any will be carefully described and analyzed The methodology to be used assuming missing at random MAR which is a reasonable assumption for this type of data and the relatively low levels of missing data we anticipate based on prior research with this population Because we have specific a priori hypotheses regarding BDNF and the composite score for executive dysfunction we will not correct for multiple comparisons Analysis of the cerebral blood flow data however will employ corrections for multiple comparisons As stated the aim of the study is to gather preliminary data regarding change from baseline to the study endpoint within the sertraline or within the PST treatment group Attrition is estimated at 20 allowing for 15 patients to complete each treatment arm
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