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

Hypertension Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01794455
• Other study ID #: VR5642
• Status: Terminated
• Phase: Phase 4
• First received: February 12, 2013
• Last updated: June 1, 2015
• Start date: May 2013
• Est. completion date: March 2015

Study information

• Verified date: June 2015
• Source: Vanderbilt University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 60 Years and older

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Hypertension

Intervention

Drug:
• Sertraline
50mg - 200mg daily
• Candesartan
4mg - 32mg daily

Locations

Country	Name	City	State
United States	Vanderbilt Psychiatric Hospital	Nashville	Tennessee

Sponsors (1)

Lead Sponsor	Collaborator
Vanderbilt University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Montgomery Asberg Depression Rating Scale (MADRS)	MADRS is a measure of depression severity. This outcome applies to the sertraline Phase 1 arm.	Week 8	No
Secondary	Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)	Self-report measure of depression severity. This applies to the sertraline Phase 1 arm.	Week 8	No
Secondary	Quick Inventory of Depressive Symptoms, Self-Rated (QIDS-SR16)	Self-report measure of depression severity. This applies to the candesartan Phase 2 arm.	Week 20	No
Secondary	Montgomery-Asberg Depression Rating Scale	MADRS is a measure of depression severity. This outcome applies to the candesartan Phase 2 arm.	Week 20	No
Secondary	MRI Arterial Spin Labeling	MRI arterial spin labeling is a noninvasive approach to measuring cerebral blood flow. This relates to the Phase 2 candesartan arm.	Change from week 8 to week 20	No