Impact of Lofexidine on Stress, Craving and Opioid Use

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Impact of Lofexidine on Stress, Craving and Opioid Use

Conditions
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Opioid-use Disorder, Opiate Dependence

Intervention / Treatment
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* Drug: Lofexidine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria 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. Exclusion Criteria 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 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lofexidine Men<br>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. | Drug: Lofexidine<br>* 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.<br>* Other names: Lucemyra;|
| Experimental: Lofexidine Women<br>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. | Drug: Lofexidine<br>* 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.<br>* Other names: Lucemyra;|
| Placebo Comparator: Placebo Men<br>Men will receive matching placebo for five weeks. | Drug: Placebo<br>* Placebo comparator.<br>|
| Placebo Comparator: Placebo Women<br>Women will receive matching placebo for five weeks. | Drug: Placebo<br>* Placebo comparator.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 10 indicating strongly agree that they crave so that higher scores indicate more craving. | Immediately following social stress and scripted imagery tasks | 
| Drug Cue+ Stressor Induced Stress Response | Participants will rate stress on a 0 to 4 Likert scale with 0 indicate not at all and 10 indicating extremely so that higher scores indicate a more robust stress response. | Immediately following social stress and scripted imagery tasks |