Impact of Lofexidine on Stress, Craving and Opioid Use

Medical University of South Carolina (MUSC)

Status and phase: Completed; Phase 2

Conditions: Opiate Dependence; Opioid-use Disorder

Treatments: Drug: Placebo; Drug: Lofexidine

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03718065

Pro00081381

2U54DA016511-16 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 112 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

1. Able to provide informed consent and function at an intellectual level sufficient to allow accurate completion of all assessment instruments.
2. 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.
3. On a stable dose of daily buprenorphine or methadone for at least 2 weeks.
4. Age 18-65.
5. Women of childbearing potential must agree to use an effective means of birth control.
6. Consent to remain abstinent from opioids during the 1-week baseline assessment period.
7. Must consent to random assignment.

Exclusion Criteria

1. Women who are pregnant, nursing or of childbearing potential and not practicing an effective means of birth control.
2. 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.
3. History of or current psychotic disorder or bipolar I affective disorder.
4. Current suicidal or homicidal ideation/risk.
5. Taking medications known to act on adrenergic systems (B-blockers; alpha agonists or antagonists)
6. Hypotensive individuals with a sitting blood pressure of < 90/50
7. QTc interval of >440 in males and > 460 in females as the combination of lofexidine plus buprenorphine may increase the QTc interval.
8. Known allergy to lofexidine
9. Unable to comply with study procedures or pose threat to study staff.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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112 participants in 4 patient groups, including a placebo group

Lofexidine Men

Experimental group

Description:

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.

Treatment:

Drug: Lofexidine

Lofexidine Women

Experimental group

Description:

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.

Treatment:

Drug: Lofexidine

Placebo Men

Placebo Comparator group

Description:

Men will receive matching placebo for five weeks.

Treatment:

Drug: Placebo

Placebo Women

Placebo Comparator group

Description:

Women will receive matching placebo for five weeks.

Treatment:

Drug: Placebo