None listed
Conditions
Brief summary
Depression is the single major unmet need in bipolar disorder and current therapies are more efficacious in mania than depression. Key biological factors in the pathophysiology of bipolar disorder may be targeted by the AT1R antagonist, candesartan. Candesartan reduces stress reactivity, impacts the HPA axis, oxidative and inflammatory stress and enhances neurogenesis; all documented pathological markers. The CADET-BD study will test the efficacy of candesartan 16 mg/day as an adjunctive treatment for bipolar depression. CADET-BD is a multi-site, double-blind, randomised, placebo-controlled 16-week trial of candesartan as an add-on to treatment as usual. We plan to recruit 240 participants aged 18 years and above with moderate to severe bipolar depressive disorder.
Sponsors
Deakin University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
I. A DSM-5 diagnosis of bipolar disorder I or II, determined using the SCID-5-RV; II. Currently experiencing a major depressive episode, determined using the SCID-5-RV III. Moderate to severe depression indexed by a MADRS score of greater than or equal to 20. If there is a delay of >7 days between screening and baseline assessments, or baseline assessment and medication commencement, the inclusion scale (MADRS) should be administered again to ensure the participant still meets eligibility criteria; IV. Aged 18 years and above; V. Have the capacity to consent to the study and to follow its instructions and procedures; VI. Participants will need to have been on stable pre-existing pharmacological or psychotherapy regimens for two weeks prior to study entry; VII. Be using effective contraception if female, sexually active and of childbearing age, VIII. Be able to speak, read, write and understand the English language, IX. Participants will be required to nominate a current treating physician, X. Willing to consent to blood collection for safety monitoring.
Exclusion criteria
I. A diagnosis of another psychotic disorder and/or current substance use disorder, assessed using the SCID-5-RV; II. Undergoing electroconvulsive therapy (ECT) or transcranial magnetic stimulus (TMS) therapy within one month of randomisation in the study; III. Known or suspected clinically unstable systemic medical disorder, including heart disease especially congestive heart failure, cerebrovascular, liver or kidney disease including renal artery stenosis; IV. Participants on current use of any AT1R blockers or ACE inhibitors medications (such as captopril, enalapril, losartan, irbesartan) will be ineligible, although previous use of these (i.e., cessation at least two weeks prior to entrance in the study) will not preclude participation; V. Systolic blood pressure less than 110mmHg at the baseline; VI. Symptoms or measures of postural hypotension (reduction in systolic blood pressure of 20mmHg or more after standing from sitting/lying for at least one minute), VII. Safety blood results not cleared by a Principal Investigator or eGFR less than 30 at the baseline; VIII. Current pregnancy or breastfeeding for females; IX. Current use of medications contraindicated with concurrent use of candesartan: aliskiren, digoxin, spironolactone, diuretics, or daily use of non-steroidal anti-inflammatory drugs (such as ibuprofen or celecoxib; PRN use will be accepted); X. Intolerance or allergy to candesartan or any of the trial preparations; XI. Current enrolment in another psychiatric intervention study. XII. Participants on lithium will be accepted on the study but will require additional monitoring of lithium levels; XIII. Participants with current suicidal ideation with a specific plan, defined as a score of 5 or 6 on the MADRS item 10.
Outcome results
None listed