Evaluating Buspirone to Treat Opioid Withdrawal

Sponsor
Johns Hopkins University (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05511909
Collaborator
(none)
100
1
3
53.5
1.9

Study Details

Study Description

Brief Summary

The investigators propose a rigorous, Phase II, three-group, placebo-controlled double-blind randomized controlled trial (RCT) to evaluate the efficacy of buspirone for both withdrawal and craving among individuals with opioid use disorder (OUD) undergoing a standardized stepwise taper. During this 10 to 12-day residential study, participants with OUD will be enrolled, stabilized on a short-acting opioid, undergo an opioid stepwise taper, and complete a post-taper observation period where participants will have the opportunity to initiate long-term buprenorphine or extended-release naltrexone.

Condition or Disease Intervention/Treatment Phase
Phase 2

Detailed Description

This R01 will conduct a rigorous and appropriately powered randomized clinical trial to evaluate the efficacy of buspirone to decrease opioid withdrawal and craving, improve treatment retention and decrease rates of relapse. The use of buspirone for opioid use disorder (OUD) is mechanistically-supported and has demonstrated initial efficacy in small clinical trials including mostly male samples. Since the latest promising results were published 15 years ago, buspirone has yet to be evaluated in a rigorous and appropriately representative and powered randomized clinical trial. Buspirone stands to provide immediate aid to unmet treatment needs among individuals with OUD because it is FDA-approved and generically available. The investigators have designed a Phase-II, three-group, double-blind, placebo controlled evaluation of buspirone for opioid withdrawal and craving during a residential stepwise opioid taper. The study will take place in a clinical research unit over 10-12 days where participants will undergo a short-term stabilization period, an opioid taper, and a post-taper observation period where participants will initiate extended release naltrexone (XR-NTX) or buprenorphine or will receive a referral to a treatment program of the participants' choice. One hundred participants with OUD and interested in completing a residential opioid taper will be enrolled and randomized to one of three conditions: (1) an opioid stepwise taper with placebo (control), (2) an opioid stepwise taper with lofexidine (positive control), and (3) an opioid stepwise taper with buspirone (experimental). Based on previous retention rates, the investigators anticipate completing 90 participants (n=30/condition). Withdrawal and tonic craving will be collected daily throughout the course of the study using standardized questionnaires. Acute craving will be assessed in a cue-induced craving task, which was developed by Co-I Huhn, once during the residential phase and once during the outpatient phase. Finally, the safety and acceptability by the study participants will be assessed through Adverse Events (AEs), abnormal ECGs, acceptability scores, and negative comments.

The Primary Aim will compare the changes in opioid withdrawal across the three conditions. The investigators hypothesize that the opioid taper + buspirone and opioid taper + lofexidine will significantly decrease withdrawal (SOWS, COWS) relative to opioid taper alone.

Secondary Aim 1 will compare changes in craving across the three conditions. The investigators hypothesize that individuals will have significantly lower tonic and cue-induced craving scores when the individuals are actively receiving opioid taper + buspirone relative to opioid taper alone and opioid taper + buspirone. Individuals who receive opioid taper + lofexidine will have significantly lower craving following cue-induced craving + stress tasks compared to opioid taper alone and opioid taper + buspirone conditions. Secondary Aim 2 will compare the safety and acceptability by the participants in the three conditions. The investigators hypothesize that buspirone will produce the fewest adverse events and instances of negative qualitative feedback and the greatest acceptability scores, followed by opioid taper + lofexidine. Opioid taper alone is expected to produce the highest number of adverse events and the lowest acceptability.

The Exploratory Aim will compare the changes in anxiety and acute stress response across the three conditions. The investigators offer no hypothesis on this aim.

This study will determine whether buspirone is an effective medication for treating opioid withdrawal and craving. This study will demonstrate the utility of using mechanistically supported medications to treat opioid withdrawal symptoms. If proven to have a positive impact on OUD and related sequelae, these data would support additional research evaluating the benefits of buspirone in other short -and long-term treatment settings for opioid use disorder. Further, this medication should be evaluated among chronic pain patients interested in tapering off of opioids but requiring additional therapeutic support to address acute and protracted withdrawal. The re-purposing of buspirone to treat OUD could occur rapidly and offers a safe pharmacotherapy for individuals requiring additional support for OUD.

Study Design

Study Type:
Interventional
Anticipated Enrollment :
100 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Evaluating a Mechanistically-Supported Pharmacotherapy to Treat Opioid Withdrawal
Anticipated Study Start Date :
Oct 15, 2022
Anticipated Primary Completion Date :
Jan 31, 2027
Anticipated Study Completion Date :
Mar 31, 2027

Arms and Interventions

Arm Intervention/Treatment
Experimental: opioid stepwise taper + buspirone

up to 45mg/day buspirone during the opioid stepwise taper

Drug: Buspirone
Buspirone administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).

Active Comparator: opioid stepwise taper + lofexidine

up to 2.16mg/day lofexidine during the opioid stepwise taper

Drug: Lofexidine
Lofexidine administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).

Placebo Comparator: opioid stepwise taper + placebo

placebo during the opioid stepwise taper

Drug: Placebo
Participants administration begins 2 days prior to opioid taper (study day -2) and continues until the second day of the post-taper observation phase (study day 7).

Outcome Measures

Primary Outcome Measures

  1. Change in Opioid Withdrawal as assessed by the Subjective Opiate Withdrawal Scale (SOWS) [Days -2 to 8]

    Opioid withdrawal severity will be measured with the Subjective Opiate Withdrawal Scale (SOWS) and will be computed as a daily peak total SOWS score for study days -2 to 8. The SOWS consists of 16 opioid withdrawal symptoms that are assessed for severity on a scale from 0-4 ("Not at all" to "Extremely"). Total scores range from 0-64 where a score between 0-10 is considered mild, between 11-20 is considered moderate, and greater than 21 is considered severe.

Secondary Outcome Measures

  1. Change in tonic craving scores [Days -2 to 8]

    Craving will be measured by tonic craving will be computed as daily peak total craving scores. The tonic craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.

  2. Change in cue-induced craving scores [Days -2 to 8]

    Cue-induced craving will be computed as total craving scores before and after the craving task. The craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.

  3. Change in stress-induced craving scores [Days -2 to 8]

    Stress-induced craving will be computed as total craving scores before and after stress/craving task. The craving assessment consists of 5 items related to craving that are completed on a visual analog scale (VAS) where 0 = not at all and 100 = A lot.

  4. Frequency of Adverse Events [Up to day 8]

    Safety will be assessed with the number of adverse events per treatment condition not including unrelated adverse events.

  5. Frequency of QTc Interval Prolongation [Up to day 8]

    Corrected QT (QTc) interval prolongation frequency will be compared across conditions. QTc interval is considered prolonged if >440 ms among male participants and >460 ms among female participants.

  6. Acceptability of buspirone for opioid withdrawal and craving [Up to day 8]

    Acceptability will be measured by acceptability questionnaires completed at discharge and will be computed as the average acceptability score. Scores range from 0-10, where 0 reflects no acceptability and 10 reflects high acceptability.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 75 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  • Aged 18-75

  • Opioid positive urine sample

  • Current moderate-severe opioid use disorder with evidence of physical dependence

  • Interested in undergoing opioid detoxification

Exclusion Criteria:
  • Being pregnant or breastfeeding

  • Enrolled in methadone or buprenorphine maintenance treatment

  • Allergic to study medication or taking medications that are contraindicated with study medication (e.g., CYP3A4 inhibitors or inducers and/or monoamine oxidase (MAO) inhibitors)

  • Significant mental health or physical disorder, or life circumstance, that is expected to interfere with study participation (detailed further in protection of human subjects form).

  • Hypotension and/or prolonged QTc interval

Contacts and Locations

Locations

Site City State Country Postal Code
1 Behavioral Pharmacology Research Unit Baltimore Maryland United States 21224

Sponsors and Collaborators

  • Johns Hopkins University

Investigators

  • Principal Investigator: Cecilia Bergeria, Ph.D., Johns Hopkins University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Johns Hopkins University
ClinicalTrials.gov Identifier:
NCT05511909
Other Study ID Numbers:
  • IRB00315529
First Posted:
Aug 23, 2022
Last Update Posted:
Aug 23, 2022
Last Verified:
Aug 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Aug 23, 2022