Effects of Cerebral Hypoperfusion and Its Reversal on Late-Life Depression

This study is currently recruiting participants. (see Contacts and Locations)
Verified May 2013 by Vanderbilt University
Sponsor:
Information provided by (Responsible Party):
Warren Taylor, Vanderbilt University
ClinicalTrials.gov Identifier:
NCT01794455
First received: February 12, 2013
Last updated: May 28, 2013
Last verified: May 2013
  Purpose

This pilot proposal will test the hypothesis that altered cerebral vessel reactivity and cerebral hypoperfusion (decreased blood flow to the brain) is a core mechanism underlying the relationship between vascular disease and depression in older adults. The long-term objective of this line of research is to: A) determine the relationship between vascular reactivity, cerebral hypoperfusion and the persistence of late-life depression and B) determine if improving cerebral perfusion with angiotensin receptor blockers (ARBs) improves depression outcomes.


Condition Intervention Phase
Depression
Hypertension
Drug: Sertraline
Drug: Candesartan
Phase 4

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Vanderbilt University:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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. 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. 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.


Estimated Enrollment: 18
Study Start Date: May 2013
Estimated Study Completion Date: February 2015
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase 1: Sertraline
Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.
Drug: Sertraline
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.
Drug: Candesartan
4mg - 32mg daily
Other Name: Atacand

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   60 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Age 60 years or older
  2. Diagnosis of Major Depressive Disorder, single or recurrent episode, without psychotic features by Diagnostic and Statistical Manual IV Text Revision (DSMIV-TR) criteria
  3. Presence of hypertension (defined as systolic > 140 or diastolic > 90 or currently receiving antihypertensive therapy)
  4. Minimum depression severity of ≥ 15 on the Montgomery-Asberg Depression Rating Scale (MADRS)
  5. Cognitively intact or with mild cognitive deficits, with a minimum score ≥ 23 on the Montreal Cognitive Assessment (MoCA).

Exclusion Criteria:

  1. Other psychiatric Axis I disorders
  2. Acute suicidality
  3. Electroconvulsive therapy in the last 6 months
  4. Primary neurological disorder, including dementia and stroke
  5. Significant cardiovascular disease, specifically diagnosis of congestive heart failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical aortic or mitral stenosis
  6. Myocardial infarction or open-heart surgery in last 6 weeks
  7. Serum creatinine ≥ 265 micromol /L
  8. Serum potassium ≥ 5.5 mmol/L
  9. MRI contraindications
  10. Known allergy to sertraline or candesartan specifically or known allergy to other SSRIs or ARBs.
  11. History of prolonged (> 3 weeks) or self-described severe discontinuation syndrome in the past after stopping an antidepressant.
  12. Current use of an angiotensin receptor blocker
  13. Current or planned psychotherapy
  14. Need for continuous oxygen use or any medical disorder where the hypercapnia challenge would be contraindicated or put the subject at increased risk. This would include acute respiratory disease, chronic angina, or other unstable cardiac conditions.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01794455

Contacts
Contact: Dean Holbert 615-322-1030 dean.holbert@vanderbilt.edu

Locations
United States, Tennessee
Vanderbilt Psychiatric Hospital Recruiting
Nashville, Tennessee, United States, 37212
Contact: Dean Holbert    615-322-1030    dean.holbert@vanderbilt.edu   
Principal Investigator: Warren D Taylor, MD, MHSc         
Sponsors and Collaborators
Vanderbilt University
Investigators
Principal Investigator: Warren D Taylor, MD, MHSc Vanderbilt University
  More Information

No publications provided

Responsible Party: Warren Taylor, Associate Professor of Psychiatry, Vanderbilt University
ClinicalTrials.gov Identifier: NCT01794455     History of Changes
Other Study ID Numbers: VR5642
Study First Received: February 12, 2013
Last Updated: May 28, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Vanderbilt University:
Depression
Depressive Disorder
Geriatrics
Hypertension

Additional relevant MeSH terms:
Depression
Depressive Disorder
Hypertension
Behavioral Symptoms
Mood Disorders
Mental Disorders
Vascular Diseases
Cardiovascular Diseases
Sertraline
Candesartan
Candesartan cilexetil
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Serotonin Agents
Physiological Effects of Drugs
Antihypertensive Agents
Cardiovascular Agents
Angiotensin II Type 1 Receptor Blockers
Angiotensin Receptor Antagonists

ClinicalTrials.gov processed this record on July 10, 2014