Candesartan as an Adjunctive Treatment for Bipolar Depression

Early Phase 1

Withdrawn

• Conditions: Bipolar Disorder Depression
• Interventions: Drug: Candesartan; Drug: Placebo

• Registration Number: NCT04430959
• Lead Sponsor: The University of Texas Health Science Center, Houston

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.

Study Timeline

• Study First Submitted: 2020-05-11
• Study First Submitted QC: 2020-06-10
• Study First Posted: 2020-06-16
• Study Start: 2020-10-01
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-19
• Last Update Posted: 2022-04-27
• Primary Completion: 2022-07-01
• Study Completion: 2022-09-01

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Candesartan first then Placebo	Candesartan	4 weeks of candesartan with crossover to the other.
Candesartan first then Placebo	Placebo	4 weeks of candesartan with crossover to the other.
Placebo first then Candesartan	Placebo	4 weeks of placebo with crossover to the other.
Placebo first then Candesartan	Candesartan	4 weeks of placebo with crossover to the other.

Primary Outcome Measures

Name	Time	Method
Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period.	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 Outcome Measures

Name	Time	Method
Clinical Global Impression - Severity scale (CGI-S) scores at the end of each treatment period.	Four weeks	The CGI-S is a 7-point scale used to rate the severity of the patient's illness at the time of assessment, compared to the clinician's past experience regarding patients with similar diagnosis
Functional Assessment Screening Tool scores at the end of each treatment period.	Four weeks	The Functional Assessment Screening Tool (FAST) identifies factors that may influence problem behaviors. It is a self-report checklist that contains 16 items, with each questions being marked as either "yes", "no", or "not applicable". The checklist is designed to identify whether maladaptive behavior is maintained in four domains: attention/preferred items, escape from tasks/activities, sensory stimulation, pain attenuation.
Hamilton Anxiety Rating Scale (HAM-A) scores at the end of each treatment period.	Four weeks	HAM-A scores range from 0-56, with higher scores indicating more severe anxiety
Young Mania Rating Scale (YMRS) at the end of each treatment period	Four weeks	The YMRS is one of the most frequently utilized rating scales to assess manic symptoms. The scale has 11 items, based on the patient's subjective report and observations made during the clinical interview. Higher scores indicate a greater severity of manic symptoms. Given the cyclic nature of BD, the YMRS will be utilized to monitor patients as for the possibility of a manic switch over each four-week treatment period.

Trial Locations

Locations (1)

The University of Texas Health Science Center at Houston; 🇺🇸 Houston, Texas, United States