Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
|Official Title:||Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression|
- MRI Arterial Spin Labeling [ Time Frame: Change in perfusion from baseline to week 8 ] [ Designated as safety issue: No ]MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.
- Montgomery Asberg Depression Rating Scale (MADRS) [ Time Frame: Week 8 ] [ Designated as safety issue: No ]MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.
- Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16) [ Time Frame: Week 8 ] [ Designated as safety issue: No ]Self-report measure of depression severity. This applies to the sertraline Phase 1 arm.
- Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16) [ Time Frame: Week 20 ] [ Designated as safety issue: No ]Self-report measure of depression severity (range 0 - 27, higher scores indicate more severe depressive symptoms). This applies to the candesartan Phase 2 arm.
- Montgomery-Asberg Depression Rating Scale [ Time Frame: Week 20 ] [ Designated as safety issue: No ]MADRS is a measure of depression severity (range 0 - 60, higher scores indicate more severe depressive symptoms). This outcome applies to the candesartan Phase 2 arm.
- MRI Arterial Spin Labeling [ Time Frame: Change from week 8 to week 20 ] [ Designated as safety issue: No ]MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 2 candesartan arm.
|Study Start Date:||May 2013|
|Study Completion Date:||March 2015|
|Primary Completion Date:||March 2015 (Final data collection date for primary outcome measure)|
Experimental: Phase 1: Sertraline
Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.
50mg - 200mg daily
Other Name: Zoloft
Experimental: Phase 2: Candesartan
For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.
4mg - 32mg daily
Other Name: Atacand
This study will examine how magnetic resonance imaging (MRI) measures of cerebral perfusion relate to antidepressant response. There are two phases to the study. In the first phase, we will examine how cerebral perfusion is related to response to sertraline, a commonly used antidepressant. In the second phase, we will examine individuals who do not respond to sertraline or other selective serotonin reuptake inhibitors (SSRI). We will examine if candesartan, an ARB, improves depression and if it does so by improving cerebral perfusion.
After providing informed consent, participants will undergo medical and psychiatric screening. Participants determined to be eligible at the screen will proceed to a baseline evaluation, which will include brief cognitive neuropsychological testing and MRI. Participants will then begin open-label sertraline for eight weeks (baseline to week 8). Dosing will begin at 50mg daily and, based on response and tolerability, can increase up to the FDA approved maximum dose of 200mg daily.
After the eight weeks, participants will be re-evaluated and complete another MRI. Those who respond to sertraline and experience remission of their depression will end their study participation. Those who do not experience remission will continue to the phase 2 open-label candesartan arm.
The candesartan arm will last for 12 weeks (week 8 to week 20). Dosing will begin at 4mg daily and can increase to a maximum dose of 32mg, based on tolerability and response. Participants will be monitored closely, and other antihypertensive medications adjusted to avoid low blood pressure. At the end of the 12-week trial, participants will again complete MRI and neuropsychological testing. Their study participation will then end.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01794455
|United States, Tennessee|
|Vanderbilt Psychiatric Hospital|
|Nashville, Tennessee, United States, 37212|
|Principal Investigator:||Warren D Taylor, MD, MHSc||Vanderbilt University|