A Pilot, Proof of Concept, Placebo-controlled Trial of Candesartan as an Adjunctive Treatment for Bipolar Depression
Overview
- Phase
- Early Phase 1
- Intervention
- Candesartan
- Conditions
- Bipolar Disorder Depression
- Sponsor
- The University of Texas Health Science Center, Houston
- Locations
- 1
- Primary Endpoint
- Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period.
- Status
- Withdrawn
- Last Updated
- 4 years ago
Overview
Brief Summary
This study will assess the safety and tolerability of Candesartan when used in patients with Bipolar Disorder, in addition to their medication treatment.
Detailed Description
Pharmacological options for the treatment of Bipolar disorder (BD) are limited and a large proportion of patients does not show adequate response to treatment, especially in the case of bipolar depression. It has been hypothesized that dysfunctions in the renin-angiotensin system (RAS) may be involved in the pathophysiology of BD. We propose a double-blind, randomized, placebo-controlled, cross-over, proof-of-concept trial to investigate the effects of candesartan, an angiotensin-II receptor antagonist capable to cross the blood-brain barrier, as an adjunctive agent in the treatment of bipolar depression. Bipolar patients on a depressive episode will be randomly assigned to undergo two consecutive 4-week treatment periods with either candesartan (4 mg daily) or placebo in a crossover study. At the beginning of each treatment period, participants will complete a resting-state functional MRI scan, to be performed 1.5 hours after the first dose of the study medication. Subjects will be followed weekly and the Montgomery-Asberg Depression Rating Scale (MADRS) will be adopted as the primary outcome measure. Response will be defined as a decrease equal or higher than 50% in the MADRS score from the time of study entry to the 4th week of each treatment period. Possible associations between changes in brain connectivity (measured through resting state functional MRI) and subsequent response to treatment will also be analyzed.
Investigators
Marsal Sanches
Associate Director, UT Health Center of Excellence on Mood Disorders
The University of Texas Health Science Center, Houston
Eligibility Criteria
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
Candesartan first then Placebo
4 weeks of candesartan with crossover to the other.
Intervention: Candesartan
Candesartan first then Placebo
4 weeks of candesartan with crossover to the other.
Intervention: Placebo
Placebo first then Candesartan
4 weeks of placebo with crossover to the other.
Intervention: Candesartan
Placebo first then Candesartan
4 weeks of placebo with crossover to the other.
Intervention: Placebo
Outcomes
Primary Outcomes
Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period.
Time Frame: Four weeks
MADRS scores range from 0-60; higher scores indicate a higher level of severity of depressive symptoms. Response will be defined as a decrease equal or higher than 50% in the total MADRS score between the baseline and the 4th week of each treatment period.
Secondary Outcomes
- Clinical Global Impression - Severity scale (CGI-S) scores at the end of each treatment period.(Four weeks)
- Functional Assessment Screening Tool scores at the end of each treatment period.(Four weeks)
- Hamilton Anxiety Rating Scale (HAM-A) scores at the end of each treatment period.(Four weeks)
- Young Mania Rating Scale (YMRS) at the end of each treatment period(Four weeks)