Assessing a Clinically-meaningful Opioid Withdrawal Phenotype

NCT ID: NCT05027919

Last Updated: 2025-09-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-01

Study Completion Date

2027-02-28

Brief Summary

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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

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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.

Conditions

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Opioid Withdrawal Opioid Use Disorder Opioid Craving

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

The order of medication pre-treatment during the two Naloxone Challenges will be blinded to participants and the investigator.

Study Groups

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Within-subject design

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).

Group Type OTHER

Hydromorphone

Intervention Type DRUG

Up to 120mg oral per day in q4 dosing to manage withdrawal

Naloxone + lofexidine pretreatment

Intervention Type DRUG

0.2-0.4mg naloxone injection during the Naloxone challenge + pretreatment with oral lofexidine (25% of max daily dose scheduled during lofexidine taper)

Naloxone + placebo pretreatment

Intervention Type DRUG

0.2-0.4mg naloxone injection during the Naloxone challenge

Lofexidine

Intervention Type DRUG

Oral Lofexidine dosed per FDA label (4 times daily) on days 6 through 10.

Interventions

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Hydromorphone

Up to 120mg oral per day in q4 dosing to manage withdrawal

Intervention Type DRUG

Naloxone + 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)

Intervention Type DRUG

Naloxone + placebo pretreatment

0.2-0.4mg naloxone injection during the Naloxone challenge

Intervention Type DRUG

Lofexidine

Oral Lofexidine dosed per FDA label (4 times daily) on days 6 through 10.

Intervention Type DRUG

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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National Institute on Drug Abuse (NIDA)

NIH

Sponsor Role collaborator

University of Maryland, Baltimore

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kelly E Dunn, Ph.D, M.B.A.

Role: PRINCIPAL_INVESTIGATOR

University of Maryland

Locations

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University of Maryland

Baltimore, Maryland, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Kelly E Dunn, Ph.D, M.B.A.

Role: CONTACT

802-922-1682

Facility Contacts

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Kelly E Dunn, PhD, MBA

Role: primary

802-922-1682

Other Identifiers

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1R01DA052937

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00279895

Identifier Type: -

Identifier Source: org_study_id

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