Back to resultsCandesartan as an Adjunctive Treatment for Bipolar Depression
Primary Purpose
Bipolar Disorder Depression
Status
Withdrawn
Phase
Early Phase 1
Locations
United States
Study Type
Interventional
Intervention
Candesartan
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder Depression
Eligibility Criteria
A diagnosis of BD type I or II, and currently in a depressive episode, based on DSM-5 criteria.
Inclusion criteria:
- Age 18 to 65 years.
- A diagnosis of BD type I or II according to DSM-5 criteria, established through the administration of the MINI.
- Currently in a depressive episode, based on DSM-5 criteria.
- MADRS >20 at entry in the study.
- 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.
- 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.
- 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:
- Current use of angiotensin receptor antagonists, angiotensin converting enzyme inhibitors. (ACE inhibitors), or a history of allergies or poor tolerability to those medications
- 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.
- Pregnancy or current breastfeeding.
- Acute systemic infections or other acute medical conditions at the time of study entry.
- 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.
- Family history of hereditary neurologic disorder.
- Unable to give informed consent for any reason.
- Floating metallic objects in the body.
- Positive urine drug screening at the time of study entry.
- Current or previous diagnosis of intellectual disability, learning disability, or other severe neurodevelopmental disorders.
- History of traumatic brain injury or head trauma with loss of consciousness for more than 30 minutes.
Sites / Locations
- The University of Texas Health Science Center at Houston
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Candesartan first then Placebo
Placebo first then Candesartan
Arm Description
4 weeks of candesartan with crossover to the other.
4 weeks of placebo with crossover to the other.
Outcomes
Primary Outcome Measures
Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period.
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
Hamilton Anxiety Rating Scale (HAM-A) scores at the end of each treatment period.
HAM-A scores range from 0-56, with higher scores indicating more severe anxiety
Clinical Global Impression - Severity scale (CGI-S) scores at the end of each treatment period.
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.
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.
Young Mania Rating Scale (YMRS) at the end of each treatment period
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.
Full Information
NCT ID
NCT04430959
First Posted
May 11, 2020
Last Updated
April 19, 2022
Sponsor
The University of Texas Health Science Center, Houston
1. Study Identification
Unique Protocol Identification Number
NCT04430959
Brief Title
Candesartan as an Adjunctive Treatment for Bipolar Depression
Official Title
A Pilot, Proof of Concept, Placebo-controlled Trial of Candesartan as an Adjunctive Treatment for Bipolar Depression
Study Type
Interventional
2. Study Status
Record Verification Date
April 2022
Overall Recruitment Status
Withdrawn
Why Stopped
The reason the study was withdrawn was due to lack of funds. In addition, the PI is moving to a different institution and it would not be feasible to proceed with the study under these circumstances.
Study Start Date
October 1, 2020 (Actual)
Primary Completion Date
July 1, 2022 (Anticipated)
Study Completion Date
September 1, 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
The University of Texas Health Science Center, Houston
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder Depression
7. Study Design
Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Candesartan first then Placebo
Arm Type
Experimental
Arm Description
4 weeks of candesartan with crossover to the other.
Arm Title
Placebo first then Candesartan
Arm Type
Placebo Comparator
Arm Description
4 weeks of placebo with crossover to the other.
Intervention Type
Drug
Intervention Name(s)
Candesartan
Other Intervention Name(s)
Atacand
Intervention Description
Candesartan 4 mg, tablets, orally, once daily for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Candesartan placebo-matching tablets, orally, once daily for 4 weeks
Primary Outcome Measure Information:
Title
Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period.
Description
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.
Time Frame
Four weeks
Secondary Outcome Measure Information:
Title
Hamilton Anxiety Rating Scale (HAM-A) scores at the end of each treatment period.
Description
HAM-A scores range from 0-56, with higher scores indicating more severe anxiety
Time Frame
Four weeks
Title
Clinical Global Impression - Severity scale (CGI-S) scores at the end of each treatment period.
Description
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
Time Frame
Four weeks
Title
Functional Assessment Screening Tool scores at the end of each treatment period.
Description
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.
Time Frame
Four weeks
Title
Young Mania Rating Scale (YMRS) at the end of each treatment period
Description
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.
Time Frame
Four weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
A diagnosis of BD type I or II, and currently in a depressive episode, based on DSM-5 criteria.
Inclusion criteria:
Age 18 to 65 years.
A diagnosis of BD type I or II according to DSM-5 criteria, established through the administration of the MINI.
Currently in a depressive episode, based on DSM-5 criteria.
MADRS >20 at entry in the study.
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.
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.
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:
Current use of angiotensin receptor antagonists, angiotensin converting enzyme inhibitors. (ACE inhibitors), or a history of allergies or poor tolerability to those medications
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.
Pregnancy or current breastfeeding.
Acute systemic infections or other acute medical conditions at the time of study entry.
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.
Family history of hereditary neurologic disorder.
Unable to give informed consent for any reason.
Floating metallic objects in the body.
Positive urine drug screening at the time of study entry.
Current or previous diagnosis of intellectual disability, learning disability, or other severe neurodevelopmental disorders.
History of traumatic brain injury or head trauma with loss of consciousness for more than 30 minutes.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marsal Sanches, MD PhD
Organizational Affiliation
University of Texas, Science Center at Houston
Official's Role
Principal Investigator
Facility Information:
Facility Name
The University of Texas Health Science Center at Houston
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Candesartan as an Adjunctive Treatment for Bipolar Depression
We'll reach out to this number within 24 hrs