Assessing a Clinically-meaningful Opioid Withdrawal Phenotype

University of Maryland Baltimore (UMB)

Status and phase: Enrolling; Phase 2

Conditions: Opioid Withdrawal; Opioid Craving; Opioid Use Disorder

Treatments: Drug: Naloxone + lofexidine pretreatment; Drug: Lofexidine; Drug: Hydromorphone; Drug: Naloxone + placebo pretreatment

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05027919

1R01DA052937 (U.S. NIH Grant/Contract)

IRB00279895

Details and patient eligibility

About

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

Full 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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

Within-subject design

Other group

Description:

All participants will undergo the same study design, which includes hydromorphone stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).

Treatment:

Drug: Naloxone + placebo pretreatment

Drug: Hydromorphone

Drug: Lofexidine

Drug: Naloxone + lofexidine pretreatment