Opioid-use DisorderPhase 2NCT03718065

Impact of Lofexidine on Stress, Craving and Opioid Use

A Phase 2 study testing Lofexidine in people with Opioid-use Disorder and Opiate Dependence, run by Medical University of South Carolina at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 60 years
Conditions the study is for: Opioid-use Disorder, Opiate Dependence
What is being tested?: Lofexidine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 112 participants
Where: 1 siteUnited States
Study dates: 26 Jun 2019to 30 Jan 2024
Phase: Phase 2
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 60 years
All sexes
No healthy volunteers
Adult

Who may be able to join

Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
Meet DSM-5 criteria for opioid use disorder (within the past three months). While individuals may also meet criteria for mild use disorders of other substances, they must identify opioids as their primary substance of abuse and must not meet criteria for any other moderate or severe substance use disorder (except tobacco, caffeine, or marijuana) within the last 60 days.
On a stable dose of daily buprenorphine or methadone for at least 2 weeks.
Age 18-65.
Women of childbearing potential must agree to use an effective means of birth control.
Consent to remain abstinent from opioids during the 1-week baseline assessment period.
Must consent to random assignment.

Who cannot join

Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
Evidence or history of major medical illnesses, including liver diseases, abnormal vaginal bleeding, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, insulin-dependent diabetes, history of stroke or other medical conditions that the investigator deems as contraindicated for the individual to be in the study.
History of or current psychotic disorder or bipolar I affective disorder.
Current suicidal or homicidal ideation/risk.
Taking medications known to act on adrenergic systems (B-blockers; alpha agonists or antagonists)
Hypotensive individuals with a sitting blood pressure of < 90/50

Show all 9Show fewer

QTc interval of >440 in males and > 460 in females as the combination of lofexidine plus buprenorphine may increase the QTc interval.
Known allergy to lofexidine
Unable to comply with study procedures or pose threat to study staff.

Trial locations and contacts

1 site in 1 country.

United States1 site

Medical University of South Carolina
Charleston, South Carolina, 29403

Other trials in United States

About this study

Individuals with opioid use disorder who are stabilized on buprenorphine or methadone will be randomly assigned to receive placebo or lofexidine for 5 weeks. At the end of five weeks, they will complete a human laboratory stress task and scripted opioid imagery task. Throughout the study a CREMA app (Cue Reactivity Ecological Momentary Assessment) will be used to monitor stress, craving and use in the natural environment.

Read the detailed description

Participants will complete a screening visit to determine study eligibility. During the first week, participants will be asked to abstain from opioid use other than buprenorphine. Participants will come to the clinic 2 times that week for urine drug testing. If all 2 tests are negative, participants will be randomly assigned to take either lofexidine or placebo (inactive medication) two to three times a day for 5 weeks. During this time, participants will upload videos of themselves taking their medication. They will come to the clinic 3 times a week for urine drug screens and to have their vital signs measured. They will also participate in "CREMA" sessions (Cue Reactivity Ecologic Momentary Assessment) 3 times a day. These sessions include looking at stressful and neutral pictures and rating stress and craving. At the end of five weeks, participants will return to the clinic and participate in a stress task and a scripted opioid imagery task the following day. For the next five days, participants will taper their medication dose. During this time they will continue to come to clinic to have their vital signs measured and complete a follow-up visit.

Conditions: Opioid-use Disorder, Opiate Dependence
Being tested: Lofexidine, Placebo
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.

LofexidineDrug
Also called Lucemyra
Lofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure, but more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist.
PlaceboDrug
Placebo comparator.

Study groups in NCT03718065
Study group	Role	What they receive
Lofexidine Men	Experimental	Men will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study. Receives: Drug: Lofexidine
Lofexidine Women	Experimental	Women will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study. Receives: Drug: Lofexidine
Placebo Men	Placebo comparator	Men will receive matching placebo for five weeks. Receives: Drug: Placebo
Placebo Women	Placebo comparator	Women will receive matching placebo for five weeks. Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Drug Cue+ Stressor Induced Craving
Participants will rate craving on a 0 to 7 Likert scale with 0 indicate "Strongly disagree" that they crave and 7 indicating "strongly agree" that they crave so that higher scores indicate more craving.
Measured: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline
Drug Cue+ Stressor Induced Stress Response
Participants will rate stress on a 0 to 4 Likert scale with 0 indicate "not at all" and 4 indicating "extremely" so that higher scores indicate a more robust stress response.
Measured: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

26 Jun 201930 Jan 2024

First posted24 Oct 2018
Study start26 Jun 2019
Primary completion30 Jan 2024
Study completion30 Jan 2024

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Opioid-use DisorderStudies of the same condition, open and under way.
More trials run by Medical University of South CarolinaThe sponsor's other registered studies.
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: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 112 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03718065
Sponsor's protocol ID: Pro00081381
Other IDs: 2U54DA016511-16
Status last verified: Feb 2025
First submitted: 23 Oct 2018
Last updated: 7 Feb 2025
Results posted: Yes, on ClinicalTrials.gov
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Guille C, King C, Ramakrishnan V, Baker N, Cortese B, Nunn L, Rogers T, McRae-Clark A, Brady K. The impact of lofexidine on stress-related opioid craving and relapse: Design and methodology of a randomized clinical trial. Contemp Clin Trials. 2021 Dec;111:106616. doi: 10.1016/j.cct.2021.106616. Epub 2021 Nov 2.
PubMed 34737091

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Impact of Lofexidine on Stress, Craving and Opioid Use
ClinicalTrials.gov ID: NCT03718065
Acronym / sponsor ID: Pro00081381
Conditions: Opioid-use Disorder, Opiate Dependence
Phase: Phase 2
Study type: Interventional
Recruitment status: Completed
Enrolment: 112 participants (actual)
Lead sponsor: Medical University of South CarolinaUniversity, hospital or other
Collaborators: National Institutes of Health (NIH), National Institute on Drug Abuse (NIDA)
Study start: 26 Jun 2019 (actual)
Primary completion: 30 Jan 2024 (actual)
Study completion: 30 Jan 2024 (actual)
First posted: 24 Oct 2018 (actual)
Results: Posted 7 Feb 2025

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4

Arm	Type	Receives
Lofexidine Men	Experimental	Drug: LofexidineMen will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study.
Lofexidine Women	Experimental	Drug: LofexidineWomen will receive lofexidine (Lucemyra) for 5 weeks. Titration schedule is as follows: 0.36 mg on the first two evenings, 0.36 mg in the morning and evening on days 3 and 4; 0.36 mg in the morning, afternoon, and at bedtime on days 5 and 6; 0.36 mg in the morning and afternoon and 0.72 mg at bedtime on days 7 and 8; 0.36 mg in the morning and 0.72 mg in the afternoon and at bedtime on days 9 and 10, and 0.72 mg in the morning, afternoon and at bedtime on Day 11 and throughout the rest of the study.
Placebo Men	Placebo comparator	Drug: PlaceboMen will receive matching placebo for five weeks.
Placebo Women	Placebo comparator	Drug: PlaceboWomen will receive matching placebo for five weeks.

Who may qualify

Ages: 18 to 60 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult

Key inclusion criteria (7 listed)

Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
Meet DSM-5 criteria for opioid use disorder (within the past three months). While individuals may also meet criteria for mild use disorders of other substances, they must identify opioids as their primary substance of abuse and must not meet criteria for any other moderate or severe substance use disorder (except tobacco, caffeine, or marijuana) within the last 60 days.
On a stable dose of daily buprenorphine or methadone for at least 2 weeks.
Age 18-65.
Women of childbearing potential must agree to use an effective means of birth control.

Key exclusion criteria (9 listed)

Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
Evidence or history of major medical illnesses, including liver diseases, abnormal vaginal bleeding, suspected or known malignancy, thrombophlebitis, deep vein thrombosis, pulmonary embolus, clotting or bleeding disorders, heart disease, insulin-dependent diabetes, history of stroke or other medical conditions that the investigator deems as contraindicated for the individual to be in the study.
History of or current psychotic disorder or bipolar I affective disorder.
Current suicidal or homicidal ideation/risk.
Taking medications known to act on adrenergic systems (B-blockers; alpha agonists or antagonists)

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
LofexidineAlso: LucemyraLofexidine, sold under the brand name Lucemyra among others, is a medication historically used to treat high blood pressure, but more commonly used to help with the physical symptoms of opioid withdrawal. It is taken by mouth. It is an α2A adrenergic receptor agonist.	Drug	Lofexidine Men, Lofexidine Women
PlaceboPlacebo comparator.	Drug	Placebo Men, Placebo Women

Primary outcome

Drug Cue+ Stressor Induced Craving
Time frame: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline
Participants will rate craving on a 0 to 7 Likert scale with 0 indicate "Strongly disagree" that they crave and 7 indicating "strongly agree" that they crave so that higher scores indicate more craving.
Drug Cue+ Stressor Induced Stress Response
Time frame: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline
Participants will rate stress on a 0 to 4 Likert scale with 0 indicate "not at all" and 4 indicating "extremely" so that higher scores indicate a more robust stress response.

Results and safety

Results posted to the registry on 7 Feb 2025, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Lofexidine Men	35	30
Lofexidine Women	24	18
Placebo Men	24	23
Placebo Women	29	25

Primary outcome: Drug Cue+ Stressor Induced Craving

Time frame: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline. Mean (Standard Deviation). Unit: units on a scale

Measure	Lofexidine Men n = 27	Lofexidine Women n = 19	Placebo Men n = 22	Placebo Women n = 23
Pre-Cue	1.52 (1.56)	1 (0)	1.72 (1.69)	1.96 (1.61)
Cue + 0 Minutes	2.33 (2.06)	3.58 (2.97)	2.05 (2.10)	3.56 (2.54)
Cue + 5 Minutes	2 (1.75)	2.74 (3.02)	1.86 (1.73)	2.83 (2.35)
Cue + 30 Minutes	1.56 (1.48)	1.68 (1.67)	1.77 (1.57)	2.09 (2.13)
Cue + 60 Minutes	1.48 (1.37)	1.32 (0.95)	1.86 (1.73)	1.87 (2.07)
Pre-TSST	1.39 (0.69)	1.11 (0.32)	1.68 (1.58)	2.19 (2.02)
TSST + 0 Minutes	1.64 (1.31)	2.72 (2.16)	2.27 (2.33)	2.95 (2.78)
TSST + 5 Minutes	1.64 (1.45)	1.89 (1.23)	2 (1.8)	2.52 (2.36)

Population analysed: Participants with available data on the Trier Social Stress Task (TSST) or Scripted Imagery Cue (Cue). TSST and Cue Tasks were counterbalanced.

Primary outcome: Drug Cue+ Stressor Induced Stress Response

Measure	Lofexidine Men n = 27	Lofexidine Women n = 19	Placebo Men n = 22	Placebo Women n = 21
Pre-Cue	2.81 (2.63)	2.74 (1.66)	2.77 (2.22)	2.65 (2.33)
Cue + 0 Minutes	3.70 (2.85)	5.37 (2.81)	3.23 (2.6)	3.61 (2.31)
Cue + 5 Minutes	2.78 (2.53)	4.16 (3.08)	2.68 (2.06)	3.09 (2)
Cue + 30 Minutes	2.56 (2.5)	2.74 (2.05)	2.59 (2.21)	2.30 (1.74)
Cue + 60 Minutes	2.63 (2.64)	2.38 (1.45)	2.64 (2.34)	2.61 (2.19)
Pre-TSST	2.57 (2.15)	2.61 (1.75)	3 (2.18)	2.57 (1.89)
TSST + 0 Minutes	4.89 (3.41)	5.78 (2.90)	3.86 (2.55)	4.95 (3.12)
TSST + 5 Minutes	3.54 (3.05)	3.61 (1.97)	2.82 (2.26)	3.10 (1.87)

Population analysed: Participants with available data on the Trier Social Stress Task (TSST) or Scripted Imagery Cue (Cue). TSST and Cue Tasks were counterbalanced.

Adverse events

Time frame: Baseline to end of study taper- 6 weeks.. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Lofexidine Men	0 of 35 (0%)	28 of 35 (80%)	0 of 35
Lofexidine Women	0 of 24 (0%)	17 of 24 (70.8%)	0 of 24
Placebo Men	0 of 24 (0%)	10 of 24 (41.7%)	0 of 24
Placebo Women	0 of 29 (0%)	13 of 29 (44.8%)	0 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 34737091Guille C, King C, Ramakrishnan V, Baker N, Cortese B, Nunn L, Rogers T, McRae-Clark A, Brady K. The impact of lofexidine on stress-related opioid craving and relapse: Design and methodology of a randomized clinical trial. Contemp Clin Trials. 2021 Dec;111:106616. doi: 10.1016/j.cct.2021.106616. Epub 2021 Nov 2.
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. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

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 Lofexidine in people with Opioid-use Disorder and Opiate Dependence, run by Medical University of South Carolina 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 7 inclusion and 9 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: finished, as of the sponsor's last update on 7 Feb 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. Some participants in this study may receive a placebo. 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?

Yes. Results are posted in the registry (first posted 7 Feb 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Drug Cue+ Stressor Induced Craving (time frame: Pre- Cue and 0, 5, 30 and 60 minutes Post-Cue 5 weeks Post- Baseline; Pre-TSST and 0, 5, 30 and 60 minutes Post-TSST 5 weeks Post-Baseline). 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?

On the ClinicalTrials.gov record for NCT03718065, which also lists 1 linked publication.

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 7 Feb 2025.