Assessing a Clinically-meaningful Opioid Withdrawal Phenotype

Phase 2

Recruiting

• Conditions: Opioid Withdrawal; Opioid Use Disorder; Opioid Craving
• Interventions: Drug: Morphine; Drug: Naloxone + lofexidine pretreatment; Drug: Naloxone + placebo pretreatment; Drug: Lofexidine

• Registration Number: NCT05027919
• Lead Sponsor: University of Maryland, Baltimore

Brief Summary

Evaluate individual differences in the expression of opioid withdrawal symptoms in persons with opioid use disorder (OUD) while completing a clinically-indicated medication taper.

Detailed Description

Individuals who have opioid use disorder and are interested in being tapered off of opioids will be admitted to a residential research unit for an 11-day period. All participants will be maintained on morphine for 5 days. During this period participants will complete 2 sessions (on two different days) wherein participants will receive an intramuscular injection of naloxone to precipitate a short withdrawal syndrome. Participants will take a capsule prior to both sessions that will contain either placebo or the opioid withdrawal medication lofexidine. Beginning on day 6 participants will be tapered off of morphine using lofexidine (as clinically indicated). At the end of the study all participants will be able to transition to buprenorphine maintenance or receive oral naltrexone and an injection of Vivitrol (extended release naltrexone), consistent with standard of care practices. Investigators will collect a variety of biological samples and questionnaire ratings during the study and primary outcomes will be measures of withdrawal collected throughout the study. Investigators will use these data to learn more about why individuals express opioid withdrawal symptoms differently, which will help inform how to change current treatment practices to be more effective for persons with OUD.

Study Timeline

• Study First Submitted: 2021-08-24
• Study First Submitted QC: 2021-08-24
• Study First Posted: 2021-08-31
• Study Start: 2022-02-01
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-28
• Last Update Posted: 2025-05-01
• Primary Completion: 2025-11-30
• Study Completion: 2026-02-28

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

• 18 years - 65 year old
• Opioid-positive urine sample
• Current opioid use disorder with evidence of physical dependence
• Interest in undergoing opioid taper

Exclusion Criteria

• Evidence of physical dependence on alcohol or benzodiazepines that requires medical intervention
• Being pregnant or breastfeeding
• Enrolled in methadone or buprenorphine maintenance treatment
• Clinically significant hypotension (<90/60mmHg) or bradycardia (<45bpm)
• History of myocardial infarction
• Subjects who are positive for hepatitis B surface antigen and/or hepatitis C antibody with liver function tests outside the normal range (persons with a positive hepatitis C antibody and normal liver functions tests are NOT excluded from the study)
• Significant mental health or physical disorder, or life circumstances, that is expected to interfere with study participation

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Within-subject design	Naloxone + lofexidine pretreatment	All participants will undergo the same study design, which includes morphine stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).
Within-subject design	Naloxone + placebo pretreatment	All participants will undergo the same study design, which includes morphine stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).
Within-subject design	Morphine	All participants will undergo the same study design, which includes morphine stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).
Within-subject design	Lofexidine	All participants will undergo the same study design, which includes morphine stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).

Primary Outcome Measures

Name	Time	Method
Withdrawal severity during lofexidine taper	Days 6 through 10	Withdrawal severity as assessed by the Subjective Opioid Withdrawal Scale. (The score range is 0 through 64) with higher score indicating more severe withdrawal.
Withdrawal severity during naloxone challenge	Days 1 through 5	Withdrawal severity as assessed by the Subjective Opioid Withdrawal scale scores (The range is 0 through 64) with higher score indicating more severe withdrawal. Collected during two naloxone challenges (pretreatment with lofexidine and pretreatment with placebo).

Trial Locations

Locations (1)

Johns Hopkins University Bayview Medical Campus; 🇺🇸 Baltimore, Maryland, United States