Opioid Craving, Opioid Use Disorder, Opioid Withdrawal
Conditions
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.
Interventions
DRUGHydromorphone
Up to 120mg oral per day in q4 dosing to manage withdrawal
DRUGNaloxone + lofexidine pretreatment
0.2-0.4mg naloxone injection during the Naloxone challenge + pretreatment with oral lofexidine (25% of max daily dose scheduled during lofexidine taper)
DRUGNaloxone + placebo pretreatment
0.2-0.4mg naloxone injection during the Naloxone challenge
DRUGLofexidine
Oral Lofexidine dosed per FDA label (4 times daily) on days 6 through 10.
Sponsors
National Institute on Drug Abuse (NIDA)
University of Maryland, Baltimore
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Masking description
The order of medication pre-treatment during the two Naloxone Challenges will be blinded to participants and the investigator.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Countries
United States
Contacts
Primary ContactKelly E Dunn, Ph.D, M.B.A.
Outcome results
None listed