Anti-suicidal Effects of Buprenorphine in Opioid Use Disorder

NCT ID: NCT04234516

Last Updated: 2021-06-18

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-01-20
• Study Completion Date: 2021-06-10

Brief Summary

The study aims to examine the effect of buprenorphine on suicidal ideation in individuals with opioid use disorder, and to investigate the functional brain activity related to its potential anti-suicidal effect.

Detailed Description

The current opioid epidemic is an urgent public health problem, contributing significantly to the climbing U.S. suicide rates over the past two decades.

Although initially rewarding, chronic opioid use leads to tolerance and escalating negative affective states. This may promote suicidal ideation and may further impair decision-making functions leading to suicidal behavior.

Buprenorphine, a treatment for opioid use disorder (OUD), has promise in reducing suicidal ideation. However, the neural mechanism of its anti-suicidal properties remains unknown. Blocking kappa opioid receptors is one mechanism of buprenorphine hypothesized to reverse the negative emotional sensitivity in OUD and thus may underlie its anti-suicidal effects.

In this morphine-controlled study, we will examine the effect of buprenorphine on the functional activity of brain regions involved in negative emotional reactivity and investigate whether this effect is associated with its anti-suicidal properties.

Buprenorphine has a different mechanism of action than currently available antidepressants and anti-suicidal medications. Understanding this mechanism can help refine its use in this context. Success will guide a future larger study to elucidate molecular mechanisms underlying anti-suicidal properties of buprenorphine.

Conditions

Opioid-use Disorder; Suicidal Ideation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Buprenorphine

Sublingual buprenorphine-naloxone films

Group Type: ACTIVE_COMPARATOR

Buprenorphine/Naloxone 8/2 milligram (mg) Sublingual Film

Intervention Type: DRUG

3 x 8 mg sublingual buprenorphine/naloxone films wrapped inside one Listerine strip at 8 pm daily + oral placebo pills q.i.d.

Morphine

Oral morphine sulphate tablets

Group Type: ACTIVE_COMPARATOR

Morphine Sulfate 30 mg

Intervention Type: DRUG

oral morphine sulphate 30 mg immediate release tablets q.i.d. + two sublingual Listerine strips at 8 pm

Interventions

Buprenorphine/Naloxone 8/2 milligram (mg) Sublingual Film

3 x 8 mg sublingual buprenorphine/naloxone films wrapped inside one Listerine strip at 8 pm daily + oral placebo pills q.i.d.

Intervention Type: DRUG

Morphine Sulfate 30 mg

oral morphine sulphate 30 mg immediate release tablets q.i.d. + two sublingual Listerine strips at 8 pm

Intervention Type: DRUG

Other Intervention Names

buprenorphine; morphine

Eligibility Criteria

Inclusion Criteria

• Age 18-55 years old
• Current opioid use disorder (mild, moderate or severe)
• Seeking treatment for opioid use disorder and willing to accept agonist-based therapy and be stabilized on buprenorphine when study is over
• Active suicidal ideation
• Participant must agree to voluntary admission to New York State Psychiatric Institute (NYSPI) inpatient research unit with confirmed bed availability
• Capacity to provide informed consent

Exclusion Criteria

• Presence of chronic pain of sufficient severity as to require ongoing pain management with opioids
• Current active psychosis or mania
• Current moderate-severe alcohol, benzodiazepine, or other drug use likely to require a medical detoxification
• Unstable epilepsy or other neurological disorder
• A history of prior head trauma with evidence of cognitive impairment. Participants who endorse a history of prior head trauma will be administered Trail-making A and B test. Those who score 1.5 standard deviations below the mean on Trail- making A or B will be excluded from study participation
• Active significant medical illness that, in the opinion of the study physician, would make study participation hazardous to the participant or compromise study findings or would prevent the participant from completing the study (e.g., uncompensated heart failure, cirrhosis or end-stage liver disease)
• Liver Function Tests (ALT, AST) greater than 5 times upper limit of normal
• On methadone-maintenance therapy
• Contraindication to any study treatment (e.g., Known allergy or sensitivity to buprenorphine)
• Pending legal action or other reasons that might prevent an individual from completing the study
• If female, currently pregnant or breastfeeding, or planning on conception
• Inadequate understanding of English
• 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 MRI scan
• Claustrophobia significant enough to interfere with MRI scanning
• Weight over 350 lbs or inability to fit into MRI scanner

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

New York State Psychiatric Institute

OTHER

Sponsor Role: lead

Responsible Party

Mina.Rizk

Paul Janssen Postdoctoral Fellow

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mina M Rizk, MD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

New York State Psychiatric Institute

New York, New York, United States

Countries

United States

Other Identifiers

IRB #7855

Identifier Type: -

Identifier Source: org_study_id