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

NCT04360681 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: AS170014-A6
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 2

Brief 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 .

Conditions

Post Traumatic Stress Disorder; Opioid-use Disorder

Keywords

Opioid Use Disorder (OUD); Opioid; Opioid Use; Post Traumatic Stress Disorder (PTSD); Veteran

Outcome Measures

Primary Outcomes (2)

• Opioid Use

  Drug-Taking Behavior (% abstinent from illicit opioid use from Week 5 to Week 12 of the active treatment phase) is the primary efficacy endpoint for monitoring the effects of treatment on OUD, which is measured by both urine drug screen (UDS; opioids are detectable for 1-4 days) and timeline follow-back (TLFB) interviews of drug/alcohol use.

  12 weeks

• PTSD Symptoms (Checklist)

  The primary efficacy endpoint for monitoring the effects of treatment on PTSD symptoms is mean change scores on the PTSD Checklist for DSM-5 (PCL-5), which is recommended by the Department of Veterans Affairs and the Department of Defense (VA/DoD) Clinical Practice Guideline as a quantitative measure of a patient's PTSD symptoms and response to treatment over time.

  12 weeks

Secondary Outcomes (2)

• Opioid Withdrawal

  12 weeks

• PTSD Symptoms

  12 weeks

Study Arms (2)

Lofexidine (LFX)

EXPERIMENTAL

LFX starting dosage is two 0.2 mg LFX tablet taken orally 2 times daily (i.e., 0.8 mg/day). At study visit 2 (Day 3), the dosage is increased to 1.2mg/day (3 tablets, BID). At visit 3 (Day 5), the dose is increased to the target dose of 1.6mg/day (4 tablets, BID). Participants enter the flexible dosing period at visit 4, at which point the LFX dose can be maintained at 1.6 mg/day or decreased to 1.2 mg/day based on symptoms and the clinical judgement of the investigator. The flexible dosing period extends through to visit 6, however, doses will be adjusted during the study as needed.

Drug: Lofexidine

Placebo (PLB)

PLACEBO COMPARATOR

A placebo drug will be employed as the comparison group to active study drug.

Drug: Placebo oral tablet

Interventions

Lofexidine DRUG

BID dosing, and a max daily dose of 1.6 mg/day

Also known as: LFX

Lofexidine (LFX)

Placebo oral tablet DRUG

Placebo

Also known as: PLB

Placebo (PLB)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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.

Sponsors & Collaborators

• Pharmacotherapies for Alcohol and Substance Use Disorders Alliance: lead
• United States Department of Defense: collaborator
• RTI International: collaborator
• Michael E. DeBakey VA Medical Center: collaborator
• USWM, LLC (dba US WorldMeds): collaborator
• Foundation for Advancing Veterans' Health Research: collaborator

Study Sites (2)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030, United States

RECRUITING

South Texas Veterans Health Care System

San Antonio, Texas, 78229, United States

RECRUITING

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic; Opioid-Related Disorders

Interventions

lofexidine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders; Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders

Study Officials

• Christopher D. Verrico, PhD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

• Thomas R Kosten, MD

  Baylor College of Medicine

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Adetola Vaughan

CONTACT

713-794-8912; adetola.vaughan@va.gov

Christopher D Verrico, PhD

CONTACT

713-791-1414; verrico@bcm.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: To minimize bias, all participants will be screened for assurance that they meet study eligibility criteria. A placebo drug will be employed as the comparison group to active study drug and the study will be conducted in a double-blinded fashion in that both the participants and the site investigators and staff interacting with participants and assessing study outcomes will be blinded to treatment assignment. The only individuals at the site with assess to treatment assignment information will be the research pharmacists.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a Phase 2 randomized, double-blind, placebo-controlled, single-site, parallel groups, 12-week treatment study

Study Record Dates

• First Submitted: April 16, 2020
• First Posted: April 24, 2020
• Study Start: March 9, 2021
• Primary Completion: December 31, 2025
• Study Completion: December 31, 2025
• Last Updated: June 8, 2025

Record last verified: 2025-06

Data Sharing

• IPD Sharing: Will share

Locations

US (2)