Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT01305889 |
Other study ID # |
10-02704 |
Secondary ID |
|
Status |
Completed |
Phase |
N/A
|
First received |
|
Last updated |
|
Start date |
March 2011 |
Est. completion date |
February 16, 2018 |
Study information
Verified date |
May 2022 |
Source |
University of California, San Francisco |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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. Mackin's 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; 2)sertraline 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.
Description:
Subjects: subjects will have non-psychotic unipolar major depression based on DSM IV criteria
(Structured Clinical Interview for DSM IV; SCID)and 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 VAMC/UCSF Center for Imaging of
Neurodegenerative Disease (CIND) under the direction of Michael Weiner, M.D. 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, Ph.D at UCSF. Serum will be assayed for BDNF
in duplicate, using a commercial BDNF ELISA assay kit (R&D 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 I/P; 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 mg/day 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 mg/day. At 8 weeks if response is limited, dose will be
increased to 150 mg/day. 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,
Ph.D.(Department of Biostatistics/Psychiatry; 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.