Lofexidine Combined With Buprenorphine for Reducing Symptoms of PTSD and OU Relapse in Veterans

Completed · Phase 2 · Has a placebo group

Conditions studied: Post Traumatic Stress Disorder, Opioid-use Disorder

In brief

The overall objective of the proposed study is to determine if lofexidine (LFX) as an adjunct to buprenorphine (BUP) treatment improves symptoms of both opioid use disorder (OUD) and Post-Traumatic Stress Disorder (PTSD). Other study objectives are to compare the safety, tolerability, and efficacy of BUP treatment alone, to BUP treatment with adjunct LFX, on measures of OUD and PTSD symptoms in Veterans with both prognosis .

Key facts

Study ID

NCT04360681

Run by

Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

People needed

84

Starts

2021-03-09

Expected to finish

2026-01-29

Last updated by the study team

2026-05-08

Who can join

Age: 18 and older, up to 70. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Male or female, 18 to 70 years of age, capable of reading and understanding English, and able to provide written informed consent (i.e. no persons who are imprisoned, of minor age, diagnosed with dementia, diagnosed with a terminal illness, or who otherwise require a surrogate to provide informed consent).
• Be on a stable dose of BUP maintenance therapy for at least 7 days at the same maintenance dose. Veterans or non-Veterans who are not currently on a stable dose of BUP maintenance therapy will be referred to the Substance Dependence Treatment Program at the MEDVAMC or the Addiction Clinic at BTGH and invited to screen for this study once BUP treatment is stable.
• Have a positive urine toxicology screen for BUP.
• Has a previous diagnosis of PTSD documented in CPRS or meets criteria for current PTSD as assessed by the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5).
• Have hematology and chemistry laboratory tests within 3 months of study entry that are within normal (± 15%) limits, except liver function test results, which can be 5X the upper limit of normal.
• Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation within 3 months of study entry.

You may not qualify if…

• DSM-5 criteria for substance use disorders (SUDs) other than OUD, nicotine, or cannabis, or stimulants [assessed by UDS and the Mini-International Neuropsychiatric Interview (MINI)].
• Note that because the MINI assesses for SUDs over the past 12 months, potential participants will only be excluded if they both meet DSM-5 criteria for a SUD and have a positive UDS for that substance on study day 1. If a participant both meets DSM-5 criteria for a SUD and has a positive UDS at the screening visit, they will be informed that to be enrolled in the study they must have a negative UDS at their first study visit (i.e., prior to being enrolled).
• Self-reported use of methadone in the last 14 days.
• Be undergoing significant opioid withdrawal, as assessed by the COWS (defined as >12 on the COWS).
• Increased risk of suicide that necessitates inpatient treatment or warrants therapy excluded by the protocol, and/or current suicidal plan, per investigator clinical judgement, based on interview and defined on the Columbia Suicidality Severity Rating Scale (C-SSRS).
• Females of child-bearing potential must be using medically acceptable birth control (e.g. oral, implantable, injectable, or transdermal contraceptives; intrauterine device; double-barrier method) AND not be pregnant OR have plans for pregnancy or breastfeeding during the study.
• Use of any of the following medications within 30 days prior to enrollment (self-report on Prior/Concomitant Medications (Meds) form):
• Benzodiazepines, barbiturates, or other CNS depressants
• Methadone or any other prescription analgesics, except BUP or BUP/naloxone
• Opioid antagonists such as naltrexone, except naloxone in combination with BUP
• Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives
• Drugs that have been associated with QT prolongation, including:
• i. Antiarrhythmics: amiodarone, ajmaline, quinidine, disopyramide, procainamide, sotalol, ibutilide, dofetilide, etc.
• ii. Antimicrobials
• Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, etc.
• Macrolides: erythromycin, roxithromycin, azithromycin, clarithromycin, etc.
• Antifungals: ketoconazole, itraconazole, etc. iii. Antipsychotics: haloperidol, thioridazine, ziprasidone, clozapine, quetiapine*, risperidone*, olanzapine, etc.
• f. Any other medications that might seriously and adversely interact with either LFX or BUP or have contraindication(s) to these medications
• The following medications will be permissible at the discretion of the study physician:
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• Bupropion a. Allowable dosage of up to 150mg daily (this is well below the therapeutic dose for depression, but is given for smoking cessation)
• Quetiapine
• a. Allowable dosage 25mg -150 mg daily (typically given at night for sleep and well below the antipsychotic dosage of 400 mg or more)
• Risperidone
• Allowable dosage 0.25mg- 1mg daily (below the antipsychotic dose of 2-8 mg daily) Prospective participants must be on a steady dose of the medication to be considered.

Where it is running

• Michael E. DeBakey Veterans Affairs Medical Center — Houston, Texas, United States
• South Texas Veterans Health Care System — San Antonio, Texas, United States

Full record on ClinicalTrials.gov

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