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

NCT01794455 | Terminated Phase 4 Results

• 1 other identifier: VR5642
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Depression; Hypertension

Keywords

Depression; Depressive Disorder; Geriatrics; Hypertension

Outcome Measures

Primary Outcomes (2)

• MRI Arterial Spin Labeling

  MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 1 sertraline arm.

  Change in perfusion from baseline to week 8

• Montgomery Asberg Depression Rating Scale (MADRS)

  MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.

  Week 8

Secondary Outcomes (4)

• Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)

  Week 8

• Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)

  Week 20

• Montgomery-Asberg Depression Rating Scale

  Week 20

• MRI Arterial Spin Labeling

  Change from week 8 to week 20

Study Arms (2)

Phase 1: Sertraline

EXPERIMENTAL

Eight-week trial of sertraline mono therapy, dosing ranging from 50mg- 200mg daily.

Drug: Sertraline

Phase 2: Candesartan

EXPERIMENTAL

For subjects who do not remit to sertraline, they will receive candesartan for 12 weeks, with doses ranging from 4mg - 32mg daily.

Drug: Candesartan

Interventions

Sertraline DRUG

50mg - 200mg daily

Also known as: Zoloft

Phase 1: Sertraline

Candesartan DRUG

4mg - 32mg daily

Also known as: Atacand

Phase 2: Candesartan

Eligibility Criteria

• Age: 60 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• Other psychiatric Axis I disorders
• Acute suicidality
• Electroconvulsive therapy in the last 6 months
• Primary neurological disorder, including dementia and stroke
• Significant cardiovascular disease, specifically diagnosis of congestive heart failure, known bilateral renal artery stenosis, symptomatic hypotension, or critical aortic or mitral stenosis
• Myocardial infarction or open-heart surgery in last 6 weeks
• Serum creatinine ≥ 265 micromol /L
• Serum potassium ≥ 5.5 mmol/L
• MRI contraindications
• Known allergy to sertraline or candesartan specifically or known allergy to other SSRIs or ARBs.
• History of prolonged (\> 3 weeks) or self-described severe discontinuation syndrome in the past after stopping an antidepressant.
• Current use of an angiotensin receptor blocker
• Current or planned psychotherapy
• 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.

Sponsors & Collaborators

• Vanderbilt University: lead

Study Sites (1)

Vanderbilt Psychiatric Hospital

Nashville, Tennessee, 37212, United States

Location

MeSH Terms

Conditions

Depression; Hypertension; Depressive Disorder

Interventions

Sertraline; candesartan; candesartan cilexetil

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior; Vascular Diseases; Cardiovascular Diseases; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

1-Naphthylamine; Amines; Organic Chemicals; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds

Limitations and Caveats

Study was ended early due to difficulty with subject recruitment. MRI data could not be obtained on that one individual due to MRI contraindications.

Results Point of Contact

• Title: Dr. Warren Taylor
• Organization: Vanderbilt University

warren.d.taylor@vanderbilt.edu

615-936-3555

Study Officials

• Warren D Taylor, MD, MHSc

  Vanderbilt University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Psychiatry

Study Record Dates

• First Submitted: February 12, 2013
• First Posted: February 18, 2013
• Study Start: May 1, 2013
• Primary Completion: March 1, 2015
• Study Completion: March 1, 2015
• Last Updated: October 20, 2016
• Results First Posted: October 20, 2016

Record last verified: 2016-08

Locations

US (1)