Bipolar Disorder DepressionEarly Phase 1NCT04430959
Candesartan as an Adjunctive Treatment for Bipolar Depression
A Early Phase 1 study testing Candesartan in people with Bipolar Disorder Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
Trial summary
This study will assess the safety and tolerability of Candesartan when used in patients with Bipolar Disorder, in addition to their medication treatment. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder Depression
- What is being tested?
- Candesartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2020to 1 Sep 2022
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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).
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Health Science Center at Houston
Houston, Texas, 77030
About this study
Official title: A Pilot, Proof of Concept, Placebo-controlled Trial of Candesartan as an Adjunctive Treatment for Bipolar Depression
This study will assess the safety and tolerability of Candesartan when used in patients with Bipolar Disorder, in addition to their medication treatment.
Read the 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
- Being tested
- Candesartan, Placebo
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CandesartanDrug
Also called Atacand
Candesartan 4 mg, tablets, orally, once daily for 4 weeks
PlaceboDrug
Candesartan placebo-matching tablets, orally, once daily for 4 weeks
| Study group | Role | What they receive |
|---|---|---|
| Candesartan first then Placebo | Experimental | 4 weeks of candesartan with crossover to the other. Receives: Drug: Candesartan; Drug: Placebo |
| Placebo first then Candesartan | Placebo comparator | 4 weeks of placebo with crossover to the other. Receives: Drug: Candesartan; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Four weeks
Secondary outcomes (4)
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
Measured: Four weeks
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
Measured: Four weeks
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.
Measured: Four weeks
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.
Measured: Four weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jun 2020
- Study start1 Oct 2020
- Primary completion1 Jul 2022 (estimated)
- Study completion1 Sep 2022 (estimated)
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Bipolar Disorder DepressionStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center, HoustonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marsal Sanches, The University of Texas Health Science Center, Houston
- Investigators
- Marsal Sanches, MD PhD, Principal investigator, University of Texas, Science Center at Houston
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04430959
- Sponsor's protocol ID
- HSC-MS-19-1046
- Status last verified
- Apr 2022
- First submitted
- 11 May 2020
- Last updated
- 27 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot, Proof of Concept, Placebo-controlled Trial of Candesartan as an Adjunctive Treatment for Bipolar Depression
- ClinicalTrials.gov ID
- NCT04430959
- Acronym / sponsor ID
- HSC-MS-19-1046
- Conditions
- Bipolar Disorder Depression
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason 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.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center, HoustonUniversity, hospital or other
- Study start
- 1 Oct 2020 (actual)
- Primary completion
- 1 Jul 2022 (estimated)
- Study completion
- 1 Sep 2022 (estimated)
- First posted
- 16 Jun 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Candesartan first then Placebo | Experimental | Drug: Candesartan, Drug: Placebo4 weeks of candesartan with crossover to the other. |
| Placebo first then Candesartan | Placebo comparator | Drug: Candesartan, Drug: Placebo4 weeks of placebo with crossover to the other. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CandesartanAlso: AtacandCandesartan 4 mg, tablets, orally, once daily for 4 weeks | Drug | Candesartan first then Placebo, Placebo first then Candesartan |
| PlaceboCandesartan placebo-matching tablets, orally, once daily for 4 weeks | Drug | Candesartan first then Placebo, Placebo first then Candesartan |
Primary outcome
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.
4 secondary outcomes
Hamilton Anxiety Rating Scale (HAM-A) scores at the end of each treatment period.
Time frame: Four weeks
Clinical Global Impression - Severity scale (CGI-S) scores at the end of each treatment period.
Time frame: Four weeks
Functional Assessment Screening Tool scores at the end of each treatment period.
Time frame: Four weeks
Young Mania Rating Scale (YMRS) at the end of each treatment period
Time frame: Four weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Marsal Sanches, MD PhD principal investigator
University of Texas, Science Center at Houston
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Candesartan in people with Bipolar Disorder Depression, run by The University of Texas Health Science Center, Houston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 27 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) scores at the end of each treatment period. (time frame: Four weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Apr 2022.