Anti-suicidal Effects of Buprenorphine in Opioid Use Disorder

Functional Brain Mechanisms Underlying the Anti-suicidal Effects of Buprenorphine in Opioid Use Disorder

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.

Study Overview

• Status: Withdrawn
• Conditions: Suicidal Ideation; Opioid-use Disorder
• Intervention / Treatment: Drug: Buprenorphine/Naloxone 8/2 milligram (mg) Sublingual Film; Drug: Morphine Sulfate 30 mg

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.

• Study Type: Interventional
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10032
      • New York State Psychiatric Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Buprenorphine; Sublingual buprenorphine-naloxone films	Drug: 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.; Other Names: buprenorphine
Active Comparator: Morphine; Oral morphine sulphate tablets	Drug: Morphine Sulfate 30 mg; oral morphine sulphate 30 mg immediate release tablets q.i.d. + two sublingual Listerine strips at 8 pm; Other Names: morphine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in Beck Scale for Suicidal Ideation (SSI) scores from baseline 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.	2 weeks
Changes in functional magnetic resonance imaging (fMRI) blood oxygen-level dependent (BOLD) signal in the amygdala in response to negative vs. neutral pictures from baseline to Week 2 post-treatment	fMRI negative picture task administered at baseline and week 2 post-treatment	2 weeks

Collaborators and Investigators

• Sponsor: New York State Psychiatric Institute
• Investigators: Principal Investigator: Mina M Rizk, MD, Columbia University

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Actual): June 10, 2021
• Study Completion (Actual): June 10, 2021

Study Registration Dates

• First Submitted: January 16, 2020
• First Submitted That Met QC Criteria: January 16, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Actual): June 18, 2021
• Last Update Submitted That Met QC Criteria: June 14, 2021
• Last Verified: June 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Chemically-Induced Disorders; Self-Injurious Behavior; Narcotic-Related Disorders; Suicide; Substance-Related Disorders; Suicidal Ideation; Opioid-Related Disorders; Physiological Effects of Drugs; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Opioid; Narcotics; Narcotic Antagonists; Buprenorphine; Naloxone; Buprenorphine, Naloxone Drug Combination; Morphine
• Other Study ID Numbers: IRB #7855

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No