Suicidal IdeationPhase 3NCT05427981
Anti-suicidal Effects of Buprenorphine In Depressed Individuals
A Phase 3 study testing Belbuca Buccal Product in people with Suicidal Ideation and Major Depressive Disorder, run by New York State Psychiatric Institute at 1 site in United States.
Trial summary
This study aims to examine the effect of low-dose buprenorphine as an add-on to treatment-as-usual for suicidal ideation in individuals with major depression, and investigate the functional brain activity related to its potential anti-suicidal effect. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Suicidal Ideation, Major Depressive Disorder
- What is being tested?
- Belbuca Buccal Product
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 10 Oct 2022to 14 Jan 2024
- Phase
- Phase 3
- 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
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female.
- Aged 18-65 years.
- Ability to take oral medication and be willing to adhere to the treatment regimen.
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- Current major depressive episode.
- Hamilton Depression Rating Scale (HDRS) Score > 16.
- Active suicidal ideation (Columbia Suicide Severity Rating Scale (C-SSRS) of 3 or more).
- Participants must have been on a medication regimen for depression that includes an adequate dose of antidepressant for at least the past 4 weeks.
Who cannot join
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current active psychosis or mania.
- Current or past alcohol use disorder or substance use disorder involving any prescribed or any illicit drug (opioid, benzodiazepine, or other drug use) including mild severity.
- Family history of alcohol or substance use disorder in a first-degree relative.
- Current or past history of prescription or non-prescription opioid use.
- History of other risk factors for the development of opioid misuse and opioid use disorder other than comorbid depression (e.g., homelessness, criminal record, aggressive or violent behavior that resulted in injury to another person).
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- Current acute or chronic pain.
- Neurological disorders (e.g., epilepsy, brain tumors or patients with increased intracranial pressure due to other reasons).
- A history of prior head trauma with evidence of cognitive impairment. Participants who endorse a history of prior head trauma will be administered the Trail-making A and B test. Those who score 1.5 standard deviations below the mean on the Trail-making A or B will be excluded from study participation.
- Active significant medical illness that would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study (e.g., oral mucositis, orthostatic hypotension, history of hypotensive disorders, hypokalemia, hypomagnesemia, or clinically unstable cardiac disease, including unstable atrial fibrillation, symptomatic bradycardia, unstable congestive heart failure, or active myocardial ischemia, history of Long QT syndrome or immediate family member with this condition, moderate to severe hepatic impairment or hepatitis, liver cirrhosis , severe chronic pulmonary diseases, significant respiratory depression, acute or severe bronchial asthma, known or suspected gastrointestinal obstruction, including paralytic ileus).
- Participants taking medications that prolong the QT interval (e.g., Class IA antiarrhythmic medications (e.g., quinidine, procainamide, disopyramide) or Class III antiarrhythmic medications (e.g., sotalol, amiodarone, dofetilide)).
- Participants taking medications with potentially clinically-significant drug interactions with BELBUCA , including benzodiazepines, central nervous system (CNS) depressants (e.g., alcohol, anxiolytics, general anaesthetics, hypnotics, neuroleptics, phenothiazines, sedatives, tranquilizers), other opioid analgesics, muscle relaxants, diuretics, anticholinergic drugs, non-nucleoside reverse transcriptase inhibitors (e.g., efavirenz, nevirapine, etravirine, delavirdine), protease inhibitors (e.g., atazanavir, ritonavir). Additionally, patients must discontinue CYP3A4 strong inhibitors (e.g., clarithromycin, telithromycin, nefazodone, itraconazole, ketoconazole) 2 weeks before initiation of the study.
- Known allergy or sensitivity to buprenorphine.
- If female, pregnancy, abortion or miscarriage in the previous two months, current breastfeeding or plans to conceive during the course of study participation. Patients who are not on contraceptives will be asked to at least use barrier methods during sexual intercourse. All patients must commit to not attempting to become pregnant during participation in the study.
- Inability to read and speak English fluently.
- Metal implants or paramagnetic objects contained within the body (including heart pacemaker, shrapnel, or surgical prostheses) which may present a risk to the subject or interfere with the MR scan, according to the guidelines set forth in the following reference book commonly used by neuroradiologists: "Guide to MR procedures and metallic objects", F. G. Shellock, Lippincott Williams and Wilkins NY 2001. Additionally, transdermal patches will be removed during the MRI.
- Claustrophobia significant enough to interfere with MRI scanning.
- Weight over 350 lbs or inability to fit into MRI scanner.
Trial locations and contacts
1 site in 1 country.
United States1 site
New York State Psychiatric Institute
New York, New York, 10032
About this study
Official title: Functional Brain Mechanisms Underlying the Anti-Suicidal Effects of Low-dose Buprenorphine in Major Depression
This study aims to examine the effect of low-dose buprenorphine as an add-on to treatment-as-usual for suicidal ideation in individuals with major depression, and investigate the functional brain activity related to its potential anti-suicidal effect.
Read the detailed description
Buprenorphine is an approved treatment for pain and opioid relapse prevention. Buprenorphine has recently shown promise in the treatment of depression and suicidal ideation relatively faster than currently available antidepressants, but its mechanisms in treating these conditions are unknown. Buprenorphine activates the mu opioid receptor in the brain and blocks the kappa opioid receptor. Activation of the mu receptors produces pleasant emotions while the kappa receptors are linked to dysphoria and other negative emotional states. By blocking kappa receptors, buprenorphine may reduce negative emotions and improve suicidal thoughts.
In this project, we will compare buprenorphine to placebo as adjunctive to usual treatments for patients who still have depression and suicidal thoughts despite being treated with adequate antidepressant medications for at least 4 weeks. We hypothesize that suicidal ideation will decrease after two weeks of treatment in the buprenorphine group relative to the placebo group.
Using functional magnetic resonance imaging, we will also examine the effects of buprenorphine on the activity of brain regions involved in the brain's response to negative emotions and test whether these effects are associated with the reduction in suicidal thoughts. This would provide some evidence that the antidepressant and anti-suicidal effects of buprenorphine are related to its kappa opioid receptor blockade.
The mechanism of action of buprenorphine is different from the currently available antidepressants. This study will help understand this mechanism which may help refine the use of buprenorphine in this context. Research in this area may also facilitate the development of new anti-suicidal treatments (i.e., other opioid-active compounds).
- Conditions
- Suicidal Ideation, Major Depressive Disorder
- Being tested
- Belbuca Buccal Product, Placebo
- Medical subject headings
- Suicidal Ideation, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Belbuca Buccal ProductDrug
Buprenorphine Buccal Films
PlaceboOther
Placebo Buccal Films
| Study group | Role | What they receive |
|---|---|---|
| Buprenorphine | Experimental | Buccal Films Receives: Drug: Belbuca Buccal Product |
| Placebo | Placebo comparator | Buccal Films Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Beck Scale for Suicidal Ideation (SSI) scores from pre- to Week 2 post-treatment.
Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted), higher scores mean more intense suicidal ideas.
Measured: 2 Weeks
Secondary outcomes (1)
Changes in functional magnetic resonance imaging (fMRI) blood oxygen- level dependent (BOLD) signal in the amygdala in response to negative vs. neutral pictures from pre- to Week 2 post-treatment
fMRI negative picture task administered at baseline and week 2 post-treatment
Measured: 2 Weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2022
- Study start10 Oct 2022
- Primary completion14 Jan 2024 (estimated)
- Study completion14 Jan 2024 (estimated)
Why it stopped: U.S. Department of Health and Human Services OHRP issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023. This study will not resume recruitment after the resumption of research.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Suicidal IdeationStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- New York State Psychiatric Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mina.Rizk, New York State Psychiatric Institute
- Investigators
- Mina M Rizk, MD, Principal investigator, New York State Psychiatric InstituteJeffrey M Miller, MD, Principal investigator, New York State Psychiatric Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05427981
- Sponsor's protocol ID
- IRB #8086
- Status last verified
- Nov 2023
- First submitted
- 16 Jun 2022
- Last updated
- 14 Nov 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Nov 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Functional Brain Mechanisms Underlying the Anti-Suicidal Effects of Low-dose Buprenorphine in Major Depression
- ClinicalTrials.gov ID
- NCT05427981
- Acronym / sponsor ID
- IRB #8086
- Conditions
- Suicidal Ideation, Major Depressive Disorder
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: U.S. Department of Health and Human Services OHRP issued an FWA restriction on NYSPI research that included a pause of human subjects research as of June 23, 2023. This study will not resume recruitment after the resumption of research.
- Enrolment
- 0 participants (actual)
- Lead sponsor
- New York State Psychiatric InstituteUniversity, hospital or other
- Study start
- 10 Oct 2022 (actual)
- Primary completion
- 14 Jan 2024 (estimated)
- Study completion
- 14 Jan 2024 (estimated)
- First posted
- 22 Jun 2022 (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 aims to examine the effect of low-dose buprenorphine as an add-on to treatment-as-usual for suicidal ideation in individuals with major depression, and investigate the functional brain activity related to its potential anti-suicidal effect.
Detailed description
Buprenorphine is an approved treatment for pain and opioid relapse prevention. Buprenorphine has recently shown promise in the treatment of depression and suicidal ideation relatively faster than currently available antidepressants, but its mechanisms in treating these conditions are unknown. Buprenorphine activates the mu opioid receptor in the brain and blocks the kappa opioid receptor. Activation of the mu receptors produces pleasant emotions while the kappa receptors are linked to dysphoria and other negative emotional states. By blocking kappa receptors, buprenorphine may reduce negative emotions and improve suicidal thoughts.
In this project, we will compare buprenorphine to placebo as adjunctive to usual treatments for patients who still have depression and suicidal thoughts despite being treated with adequate antidepressant medications for at least 4 weeks. We hypothesize that suicidal ideation will decrease after two weeks of treatment in the buprenorphine group relative to the placebo group.
Using functional magnetic resonance imaging, we will also examine the effects of buprenorphine on the activity of brain regions involved in the brain's response to negative emotions and test whether these effects are associated with the reduction in suicidal thoughts. This would provide some evidence that the antidepressant and anti-suicidal effects of buprenorphine are related to its kappa opioid receptor blockade.
The mechanism of action of buprenorphine is different from the currently available antidepressants. This study will help understand this mechanism which may help refine the use of buprenorphine in this context. Research in this area may also facilitate the development of new anti-suicidal treatments (i.e., other opioid-active compounds).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Buprenorphine | Experimental | Drug: Belbuca Buccal ProductBuccal Films |
| Placebo | Placebo comparator | Other: PlaceboBuccal Films |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
- Provision of signed and dated informed consent form.
- Stated willingness to comply with all study procedures and availability for the duration of the study.
- Male or female.
- Aged 18-65 years.
Key exclusion criteria (18 listed)
- An individual who meets any of the following criteria will be excluded from participation in this study:
- Current active psychosis or mania.
- Current or past alcohol use disorder or substance use disorder involving any prescribed or any illicit drug (opioid, benzodiazepine, or other drug use) including mild severity.
- Family history of alcohol or substance use disorder in a first-degree relative.
- Current or past history of prescription or non-prescription opioid use.
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 |
|---|---|---|
| Belbuca Buccal ProductBuprenorphine Buccal Films | Drug | Buprenorphine |
| PlaceboPlacebo Buccal Films | Other | Placebo |
Primary outcome
Changes in Beck Scale for Suicidal Ideation (SSI) scores from pre- to Week 2 post-treatment.
Time frame: 2 Weeks
Clinician-based questionnaire measuring level of suicidal ideas over the last 7 days; 21 items scored 0 to 2; total score ranges from 0 to 38 (last 2 items not counted), higher scores mean more intense suicidal ideas.
1 secondary outcome
Changes in functional magnetic resonance imaging (fMRI) blood oxygen- level dependent (BOLD) signal in the amygdala in response to negative vs. neutral pictures from pre- to Week 2 post-treatment
Time frame: 2 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 14 Nov 2023.
- Individual participant dataSharing planned: No
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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.
Mina M Rizk, MD principal investigator
New York State Psychiatric Institute
Jeffrey M Miller, MD principal investigator
New York State Psychiatric Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Belbuca Buccal Product in people with Suicidal Ideation and Major Depressive Disorder, run by New York State Psychiatric Institute 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 10 inclusion and 18 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 14 Nov 2023. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
Changes in Beck Scale for Suicidal Ideation (SSI) scores from pre- to Week 2 post-treatment. (time frame: 2 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 14 Nov 2023.