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

• Status: Recruiting
• Trial end date: 2023-02-28
• Target enrollment: 0
• Participant gender: All

Summary

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 .

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Pharmacotherapies for Alcohol and Substance Abuse Consortium
• Collaborators: Michael Debakey Veterans Affairs Medical Center; Michael E. DeBakey VA Medical Center; RTI International; United States Department of Defense; US WorldMeds LLC
• Treatments: Lofexidine

Criteria

Inclusion Criteria:

• Male or female, 18 to 65 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 who are not currently on a stable dose of BUP maintenance therapy will be referred to the Substance Dependence Treatment Program at the MEDVAMC and invited to screen for this study once BUP treatment is stable.

• Have a positive urine toxicology screen for BUP.

• Meet 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 (± 10%) 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.

Exclusion Criteria:

• 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):

• Inducers or inhibitors of cytochrome P-450 3A4 (CYP3A4), the main metabolic enzyme of BUP:

• Antiretrovirals or other strong CYP3A4 inhibitors: boceprevir, cobicistat, conivaptan, danoprevir and ritonavir, elvitegravir and ritonavir, grapefruit juice, indinavir and ritonavir, itraconazole, ketoconazole, lopinavir and ritonavir, paritaprevir and ritonavir and ombitasvir and/or dasabuvir, posaconazole, ritonavir, saquinavir and ritonavir, telaprevir, tipranavir and ritonavir, troleandomycin, voriconazole, clarithromycin, diltiazem, idelalisib, nefazodone, nelfinavir, etc.

• Moderate CYP3A4 inhibitors: aprepitant, cimetidine, ciprofloxacin, clotrimazole, crizotinib, cyclosporine, dronedarone, erythromycin, fluconazole, fluvoxamine, imatinib, tofisopam, verapamil, etc.

• Anticonvulsants or other strong CYP3A4 inducers: carbamazepine, enzalutamide, mitotane, phenytoin, rifampin, St. John's wort, etc.

• Benzodiazepines, barbiturates, or other CNS depressants

• Adrenergic antihypertensives

• 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:

• Antiarrhythmics: amiodarone, ajmaline, quinidine, disopyramide, procainamide, sotalol, ibutilide, dofetilide, etc.

• Antimicrobials

• Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, etc.

• Macrolides: erythromycin, roxithromycin, azithromycin, clarithromycin, etc.

• Antifungals: ketoconazole, itraconazole, etc.

• Antipsychotics: haloperidol, thioridazine, ziprasidone, clozapine, quetiapine, risperidone, olanzapine, etc.

• Any other medications that might seriously and adversely interact with either LFX or BUP or have contraindication(s) to these medications

• Clinically significant abnormal ECG (such as second- or third-degree heart block, QTc interval ≥500 msec, uncontrolled arrhythmia), and/or history of a myocardial infarction.

• Heart rate < 55 bpm or symptomatic bradycardia.

• Systolic blood pressure < 90 mmHg, and/or diastolic blood pressure < 60 mmHg, and/or symptomatic hypotension.

• Have a history of seizure disorder or severe traumatic brain injury (TBI); per the Ohio State TBI assessment.

• Self-reported HIV/AIDS, active tuberculosis, and/or active syphilis.

• Have significant hepatic, pancreatic (e.g., Type I diabetes), gastrointestinal or renal (that would affect absorption, metabolism or excretion of the study drug), endocrine, cardiac, neurological, psychiatric, pulmonary, hematologic, or other disorders (self-reported during Medical History assessment) that a study clinician believes would make study participation unsafe, treatment compliance difficult, or otherwise be determined by the PI to not be a good study candidate.