Opioid WithdrawalPhase 2NCT05027919
Assessing a Clinically-meaningful Opioid Withdrawal Phenotype
A Phase 2 study testing Hydromorphone, Naloxone + lofexidine pretreatment and Lofexidine in people with Opioid Withdrawal and Opioid Use Disorder, run by University of Maryland, Baltimore at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Opioid Withdrawal, Opioid Use Disorder, Opioid Craving
- What is being tested?
- Hydromorphone, Naloxone + lofexidine pretreatment and Lofexidine
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 28 Feb 2027
- Phase
- Phase 2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 18 years - 65 year old
- Opioid-positive urine sample
- Current opioid use disorder with evidence of physical dependence
- Interest in undergoing opioid taper
Who cannot join
- 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 locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
University of Maryland
Baltimore, Maryland, 21201
Kelly E Dunn, PhD, MBA, 802-922-1682, kelly.dunn@som.umaryland.edu
Kelly E Dunn, PhD, MBA
About this study
Evaluate individual differences in the expression of opioid withdrawal symptoms in persons with opioid use disorder (OUD) while completing a clinically-indicated medication taper.
Read the 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.
- Conditions
- Opioid Withdrawal, Opioid Use Disorder, Opioid Craving
- Being tested
- Hydromorphone, Naloxone + lofexidine pretreatment, Naloxone + placebo pretreatment, Lofexidine
- Medical subject headings
- Opioid-Related Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydromorphoneDrug
Up to 120mg oral per day in q4 dosing to manage withdrawal
Naloxone + lofexidine pretreatmentDrug
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 pretreatmentDrug
0.2-0.4mg naloxone injection during the Naloxone challenge
LofexidineDrug
Oral Lofexidine dosed per FDA label (4 times daily) on days 6 through 10.
| Study group | Role | What they receive |
|---|---|---|
| Within-subject design | Other | 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). Receives: Drug: Hydromorphone; Drug: Naloxone + lofexidine pretreatment; Drug: Naloxone + placebo pretreatment; Drug: Lofexidine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Withdrawal severity during lofexidine taper
Withdrawal severity as assessed by the Subjective Opioid Withdrawal Scale. (The score range is 0 through 64) with higher score indicating more severe withdrawal.
Measured: Days 6 through 10
Withdrawal severity during naloxone challenge
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).
Measured: Days 1 through 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Aug 2021
- Study start1 Dec 2021
- Primary completion30 Nov 2026 (estimated)
- Study completion28 Feb 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Opioid WithdrawalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Sponsor
- Investigators
- Kelly E Dunn, Ph.D, M.B.A., Principal investigator, University of Maryland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05027919
- Sponsor's protocol ID
- IRB00279895
- Other IDs
- 1R01DA052937
- Status last verified
- Sep 2025
- First submitted
- 24 Aug 2021
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessing a Clinically-meaningful Opioid Withdrawal Phenotype
- ClinicalTrials.gov ID
- NCT05027919
- Acronym / sponsor ID
- IRB00279895
- Conditions
- Opioid Withdrawal, Opioid Use Disorder, Opioid Craving
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 30 Nov 2026 (estimated)
- Study completion
- 28 Feb 2027 (estimated)
- First posted
- 31 Aug 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Within-subject design | Other | Drug: Hydromorphone, Drug: Naloxone + lofexidine pretreatment, Drug: Naloxone + placebo pretreatment, Drug: LofexidineAll 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). |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 18 years - 65 year old
- Opioid-positive urine sample
- Current opioid use disorder with evidence of physical dependence
- Interest in undergoing opioid taper
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydromorphoneUp to 120mg oral per day in q4 dosing to manage withdrawal | Drug | Within-subject design |
| Naloxone + lofexidine pretreatment0.2-0.4mg naloxone injection during the Naloxone challenge + pretreatment with oral lofexidine (25% of max daily dose scheduled during lofexidine taper) | Drug | Within-subject design |
| Naloxone + placebo pretreatment0.2-0.4mg naloxone injection during the Naloxone challenge | Drug | Within-subject design |
| LofexidineOral Lofexidine dosed per FDA label (4 times daily) on days 6 through 10. | Drug | Within-subject design |
Primary outcome
Withdrawal severity during lofexidine taper
Time frame: 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
Time frame: 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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kelly E Dunn, Ph.D, M.B.A. principal investigator
University of Maryland
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydromorphone, Naloxone + lofexidine pretreatment and Lofexidine in people with Opioid Withdrawal and Opioid Use Disorder, run by University of Maryland, Baltimore at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kelly E Dunn, Ph.D, M.B.A. (802-922-1682, kelly.dunn@som.umaryland.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Withdrawal severity during lofexidine taper (time frame: Days 6 through 10). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.