Candesartan as an Adjunctive Treatment for Bipolar Depression

NCT ID: NCT04430959

Last Updated: 2022-04-27

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: EARLY_PHASE1
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-10-01
• Study Completion Date: 2022-09-01

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.

Conditions

Bipolar Disorder Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Candesartan first then Placebo

4 weeks of candesartan with crossover to the other.

Group Type: EXPERIMENTAL

Candesartan

Intervention Type: DRUG

Candesartan 4 mg, tablets, orally, once daily for 4 weeks

Placebo

Intervention Type: DRUG

Candesartan placebo-matching tablets, orally, once daily for 4 weeks

Placebo first then Candesartan

4 weeks of placebo with crossover to the other.

Group Type: PLACEBO_COMPARATOR

Candesartan

Intervention Type: DRUG

Candesartan 4 mg, tablets, orally, once daily for 4 weeks

Placebo

Intervention Type: DRUG

Candesartan placebo-matching tablets, orally, once daily for 4 weeks

Interventions

Candesartan

Candesartan 4 mg, tablets, orally, once daily for 4 weeks

Intervention Type: DRUG

Placebo

Candesartan placebo-matching tablets, orally, once daily for 4 weeks

Intervention Type: DRUG

Other Intervention Names

Atacand

Eligibility Criteria

Inclusion Criteria

1. Age 18 to 65 years.

2. A diagnosis of BD type I or II according to DSM-5 criteria, established through the administration of the MINI.

3. Currently in a depressive episode, based on DSM-5 criteria.

4. MADRS >20 at entry in the study.

5. No history of hypertension, diabetes, stroke, liver, kidney, heart disease, bleeding disorders, cancer, hypothyroidism, auto-immune diseases, and any brain disorder (seizure disorder, stroke, dementia, or neurodegenerative diseases), as well as other conditions that could impact patient's safety associated with participation in the study.

6. On therapeutic doses of a mood stabilizing drug (anticonvulsants or atypical antipsychotics, but not lithium) or combinations of medications (including antidepressants, as long as receiving at least one mood stabilizing agent) for at least two weeks.

7. Allowed psychiatric comorbid conditions, such as anxiety disorders, PTSD and past history of substance use (as long as do NOT meet abuse or dependence criteria according to the SCID-I in the past 2 months).

Exclusion Criteria

1. Current use of angiotensin receptor antagonists, angiotensin converting enzyme inhibitors. (ACE inhibitors), or a history of allergies or poor tolerability to those medications

2. Current use of lithium or any other medications that could implicate in potentially dangerous. interactions with candesartan, based on available literature and the investigator's judgement.

3. Pregnancy or current breastfeeding.

4. Acute systemic infections or other acute medical conditions at the time of study entry.

5. Acute suicidal or homicidal ideation or other imminent concerns about safety, based on the investigator's judgement and/or on a score equal or higher than 4 in the item 10 of the MADRS.

6. Family history of hereditary neurologic disorder.

7. Unable to give informed consent for any reason.

8. Floating metallic objects in the body.

9. Positive urine drug screening at the time of study entry.

10. Current or previous diagnosis of intellectual disability, learning disability, or other severe neurodevelopmental disorders.

11. History of traumatic brain injury or head trauma with loss of consciousness for more than 30 minutes.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role: lead

Responsible Party

Marsal Sanches

Associate Director, UT Health Center of Excellence on Mood Disorders

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marsal Sanches, MD PhD

Role: PRINCIPAL_INVESTIGATOR

University of Texas, Science Center at Houston

Locations

The University of Texas Health Science Center at Houston

Houston, Texas, United States

Countries

United States

Other Identifiers

HSC-MS-19-1046

Identifier Type: -

Identifier Source: org_study_id