Bipolar DisorderPhase 2IsradipineNCT01784666
Adjunctive Isradipine for the Treatment of Bipolar Depression
A Phase 2 study testing Isradipine in people with Bipolar Disorder, run by Massachusetts General Hospital at 1 site in United States.
Trial summary
This study investigates the medication isradipine, which is currently approved by the FDA to treat high blood pressure, in the treatment of depression in bipolar disorder. Isradipine or placebo (contains no active medication) will be used as an "add-on" to lithium, valproate, and/or atypical antipsychotics for… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Isradipine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2013to Apr 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 18-65
- written informed consent
- meets Diagnostic and Statistical Manual-IV (DSM-IV) criteria (by Structured Clinical Interview for Diagnostic and Statistical Manual - IV -I/P (SCID)) for bipolar I disorder, current episode depressed
- Montgomery-Asberg Depression Scale (MADRS) score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
- Young Mania Rating Scale (YMRS) score < 12 at screen and baseline visit
- currently treated with a lithium preparation (carbonate or citrate) at stable dose for at least 4 wks with level >0.6 and <1.0; and/or valproate at stable dose for at least 4 wks at level >60 and <110; and/or other atypical antipsychotic at stable dose for at least 4 weeks (at least minimum FDA-labeled dose)
- Caucasian by self-report - please see discussion below
Who cannot join
- Psychotic features in the current episode, as assessed by YMRS item #8 > 6 [where treatment guidelines urge use of antipsychotics that may confound isradipine results]
- felt by the study clinician to require inpatient hospitalization for adequate management (to include serious suicide or homicide risk, as assessed by evaluating clinician)
- 3 or more failed pharmacologic interventions in the current major depressive episode, excluding lithium/valproate/other atypical antipsychotic [response rates for these subjects is likely to be extremely low and would require a substantially larger-scale study to identify treatment effects]
- obsessive-compulsive disorder, or any diagnosis of a DSM-IV anxiety disorder where the anxiety disorder and not bipolar disorder is the primary focus of clinical attention
- current substance use disorder other than nicotine, by SCID-I/P
- a primary clinical diagnosis of a personality disorder, or comorbid diagnosis of antisocial or borderline personality disorder
Show all 16Show fewer
- pregnant women or women of child bearing potential who are not using a medically accepted means of contraception (to include oral contraceptive or implant, condom, diaphragm, spermicide, intrauterine device, tubal ligation, or partner with vasectomy)
- women who are breastfeeding
- other unstable medical illness including cardiovascular, hepatic, renal, respiratory, endocrine, neurological, or hematological disease, based on review of medical history, physical examination, and screening laboratory tests (this will include any clinical or laboratory evidence of hypothyroidism; if maintained on thyroid medication must be euthyroid for at least 1 month before Visit 1)
- history of hypertension or current treatment for hypertension
- current use of isradipine or history of anaphylactic reaction or intolerance to isradipine or any component of the preparation
- ECG abnormalities at entry: prolonged QTC interval or complete or incomplete bundle branch block
- patients who have taken an investigational psychotropic drug within the last 3 months
- patients receiving other excluded antipsychotics or antidepressants within 2 weeks prior to study entry
- patients requiring continued treatment with excluded medications (see below).
- Excluded medications: antidepressants, antipsychotics, and anticonvulsants (other than valproate), which could influence calcium signaling or impact mood; other calcium channel blockers; any other antihypertensive because of the risk of cause hypotension; any other drug known to interact with isradipine. Benzodiazepines or other sedative-hypnotic agents (e.g., zolpidem) may not be initiated after study entry; subjects requiring these agents will be removed from the study. Allowed: Sedative-hypnotic agents if dosage has been stable for 4 weeks prior to study entry; thyroid or estrogen replacement provided dosage has been stable for 3 months. Acceptable anticonvulsants include lamotrigine, valproate, gabapentin, topiramate, oxcarbazepine, carbamazepine.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital
Boston, Massachusetts, 02114
About this study
This study investigates the medication isradipine, which is currently approved by the FDA to treat high blood pressure, in the treatment of depression in bipolar disorder. Isradipine or placebo (contains no active medication) will be used as an "add-on" to lithium, valproate, and/or atypical antipsychotics for individuals currently experiencing a major depressive episode. Our hypothesis is that isradipine will be superior to placebo in improving depressive symptoms.
Read the detailed description
Primary Aim: To estimate the antidepressant efficacy of isradipine versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotics among individuals with bipolar I disorder in a nonpsychotic major depressive episode.
Hypothesis: Isradipine will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).
- Conditions
- Bipolar Disorder
- Being tested
- Isradipine, Placebo
- Keywords
- Bipolar Disorder, Depression, Lithium, Valproate, Isradipine
- Medical subject headings
- Bipolar Disorder, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IsradipineDrug
The study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to isradipine versus placebo add-on for 4 weeks, with the placebo nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the isradipine treatment effect. Subjects who respond in phase 1, and all subjects who receive isradipine in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed.
PlaceboDrug
Subjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to isradipine vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed.
| Study group | Role | What they receive |
|---|---|---|
| Isradipine-Isradipine | Experimental | Subjects will receive isradipine in phase 1 (4 weeks) and phase 2 (4 weeks) Receives: Drug: Isradipine |
| Placebo -> Isradipine | Experimental | Placebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the next 4 weeks Receives: Drug: Isradipine; Drug: Placebo |
| Placebo-Placebo | Placebo comparator | Placebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the subsequent 4 weeks Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in MADRS (4 Weeks)
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in isradipine-treated epochs versus placebo-treated epochs.
These scores represent total scores, and on the MADRS total scores range from 0-60. A higher score indicates increased depression severity.
Measured: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2013 (estimated)
- Study startFeb 2013
- Primary completionApr 2014
- Study completionApr 2014
Why it stopped: Lack of Enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe 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
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Roy Perlis, Massachusetts General Hospital
- Investigators
- Roy H Perlis, MD, MSc, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01784666
- Sponsor's protocol ID
- 2012-P-002449/1
- Acronym
- Isradipine
- Status last verified
- Apr 2017
- First submitted
- 4 Feb 2013
- Last updated
- 20 Apr 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 20 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Adjunctive Isradipine for the Treatment of Bipolar Depression
- ClinicalTrials.gov ID
- NCT01784666
- Acronym / sponsor ID
- Isradipine / 2012-P-002449/1
- Conditions
- Bipolar Disorder
- Keywords
- Bipolar Disorder, Depression, Lithium, Valproate, Isradipine
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of Enrollment
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Study start
- Feb 2013
- Primary completion
- Apr 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 6 Feb 2013 (estimated)
- Results
- Posted 20 Apr 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study investigates the medication isradipine, which is currently approved by the FDA to treat high blood pressure, in the treatment of depression in bipolar disorder. Isradipine or placebo (contains no active medication) will be used as an "add-on" to lithium, valproate, and/or atypical antipsychotics for individuals currently experiencing a major depressive episode. Our hypothesis is that isradipine will be superior to placebo in improving depressive symptoms.
Detailed description
Primary Aim: To estimate the antidepressant efficacy of isradipine versus placebo as an adjunct to lithium, valproate, and/or other atypical antipsychotics among individuals with bipolar I disorder in a nonpsychotic major depressive episode.
Hypothesis: Isradipine will be superior to placebo in improvement of depressive symptoms assessed by the Montgomery-Asberg Depression Rating Scale (MADRS).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Isradipine-Isradipine | Experimental | Drug: IsradipineSubjects will receive isradipine in phase 1 (4 weeks) and phase 2 (4 weeks) |
| Placebo -> Isradipine | Experimental | Drug: Isradipine, Drug: PlaceboPlacebo non-responders after the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the next 4 weeks |
| Placebo-Placebo | Placebo comparator | Drug: PlaceboPlacebo nonresponders for the 1st 4 weeks will be re-randomized 1:1 to placebo or isradipine for the subsequent 4 weeks |
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 18-65
- written informed consent
- meets Diagnostic and Statistical Manual-IV (DSM-IV) criteria (by Structured Clinical Interview for Diagnostic and Statistical Manual - IV -I/P (SCID)) for bipolar I disorder, current episode depressed
- Montgomery-Asberg Depression Scale (MADRS) score of at least 20 (i.e., moderate depression) and no greater than 34 (i.e., severe depression) at screen and baseline visit
- Young Mania Rating Scale (YMRS) score < 12 at screen and baseline visit
Key exclusion criteria (16 listed)
- Psychotic features in the current episode, as assessed by YMRS item #8 > 6 [where treatment guidelines urge use of antipsychotics that may confound isradipine results]
- felt by the study clinician to require inpatient hospitalization for adequate management (to include serious suicide or homicide risk, as assessed by evaluating clinician)
- 3 or more failed pharmacologic interventions in the current major depressive episode, excluding lithium/valproate/other atypical antipsychotic [response rates for these subjects is likely to be extremely low and would require a substantially larger-scale study to identify treatment effects]
- obsessive-compulsive disorder, or any diagnosis of a DSM-IV anxiety disorder where the anxiety disorder and not bipolar disorder is the primary focus of clinical attention
- current substance use disorder other than nicotine, by SCID-I/P
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 |
|---|---|---|
| IsradipineThe study uses the Sequential Parallel Comparison design (SPCD), with two 4-week phases: n=30 subjects are randomized 1:1 to isradipine versus placebo add-on for 4 weeks, with the placebo nonresponders re-randomized 1:1 for a further 4 weeks. The SPCD will allow us to pool data from both phases to estimate the isradipine treatment effect. Subjects who respond in phase 1, and all subjects who receive isradipine in phase 1, continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. | Drug | Isradipine-Isradipine, Placebo -> Isradipine |
| PlaceboSubjects (n=15) are randomized to placebo add-on for 4 weeks, with the nonresponders re-randomized 1:1 to isradipine vs placebo for a further 4 weeks. Subjects who respond in phase 1 continue blinded treatment in phase 2 to preserve the blind, but only phase 1 results are analyzed. | Drug | Placebo -> Isradipine, Placebo-Placebo |
Primary outcome
Change in MADRS (4 Weeks)
Time frame: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4)
Change in Montgomery-Asberg Depression Rating Scale (MADRS) in isradipine-treated epochs versus placebo-treated epochs. These scores represent total scores, and on the MADRS total scores range from 0-60. A higher score indicates increased depression severity.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Apr 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Bipolar Disorder
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)
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.
Roy H Perlis, MD, MSc principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Isradipine in people with Bipolar Disorder, run by Massachusetts General Hospital 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 16 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: stopped early, as of the sponsor's last update on 20 Apr 2017. 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?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in MADRS (4 Weeks) (time frame: Baseline vs week 4 (and, for placebo nonresponders in 1st 4 weeks, week 8 vs week 4)). 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 20 Apr 2017.