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Purpose

This study will assess the safety and tolerability of Candesartan when used in patients with Bipolar Disorder, in addition to their medication treatment.

Condition

Eligibility

Eligible Ages
Between 18 Years and 65 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Crossover Assignment
Primary Purpose
Treatment
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
Candesartan first then Placebo 		4 weeks of candesartan with crossover to the other.
  • Drug: Candesartan
    Candesartan 4 mg, tablets, orally, once daily for 4 weeks
    Other names:
    • Atacand
  • Drug: Placebo
    Candesartan placebo-matching tablets, orally, once daily for 4 weeks
Placebo Comparator
Placebo first then Candesartan 		4 weeks of placebo with crossover to the other.
  • Drug: Candesartan
    Candesartan 4 mg, tablets, orally, once daily for 4 weeks
    Other names:
    • Atacand
  • Drug: Placebo
    Candesartan placebo-matching tablets, orally, once daily for 4 weeks

More Details

Status
Withdrawn
Sponsor
The University of Texas Health Science Center, Houston

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.