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Post Traumatic Stress DisorderPhase 2NCT04360681

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

A Phase 2 study testing Lofexidine in people with Post Traumatic Stress Disorder and Opioid-use Disorder, run by Pharmacotherapies for Alcohol and Substance Use Disorders Alliance at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 to 70 years
What is being tested?
Lofexidine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
84 participants
Where
2 sitesUnited States
Study dates
9 Mar 2021to 29 Jan 2026
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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:
  • 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. iii. 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
  • The following medications will be permissible at the discretion of the study physician:
  • <!-- -->
  • 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
  • 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.
  • 7. Prescription of any of the following medications within 30 days prior to enrollment (review of EDC patient chart):
  • Inducers or inhibitors of cytochrome P-450 3A4 (CYP3A4), the main metabolic enzyme of BUP: i. 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.
  • 8. 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.
  • 9. Heart rate < 55 bpm or symptomatic bradycardia.
  • 10. Systolic blood pressure < 90 mmHg, and/or diastolic blood pressure < 60 mmHg, and/or symptomatic hypotension.
  • 11. Have a history of seizure disorder or severe traumatic brain injury (TBI); per the Ohio State TBI assessment.
  • 12. Self-reported HIV/AIDS, active tuberculosis, and/or active syphilis.
  • 13. 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.
  • The following conditions will be permissible at the discretion of the study physician:
  • Type I \&II diabetes- participants must meet the following criteria:
  • 1. Participants must be receiving MAT for at least 6 months 2. Hemoglobin A1c levels must be stable and relatively low 3 months prior to study entry and at the time of screening ii. Pancreatitis
  • 1. There must be 12 months between enrollment and last pancreatitis episode iii. Hepatitis
  • 1. Lab work submitted 3 months prior to study entry and at the time of screening should exhibit no elevations in liver functioning tests beyond 3X the upper limit of normal

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • Michael E. DeBakey Veterans Affairs Medical Center

    Houston, Texas, 77030

  • South Texas Veterans Health Care System

    San Antonio, Texas, 78229

Other trials in United States

About this study

Official title: Lofexidine Combined With Buprenorphine for Reducing Symptoms of Post-Traumatic Stress Disorder (PTSD) and Opioid Use Relapse in Veterans

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 .

Read the detailed description

The aim of this clinical trial is to evaluate the efficacy of Lucemyra™ (lofexidine; LFX), an alpha-2-adrenergic receptor (α2-AR) agonist, as a medication for the prevention of opiate relapse and the alleviation of post-traumatic stress disorder (PTSD) symptoms in opiate-dependent veterans.

Primary Endpoints :

For OUD:

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.

For PTSD:

The primary efficacy endpoint for monitoring the effects of treatment on PTSD symptoms is mean change scores on the PTSD Checklist for Diagnostic and Statistical Manual of Mental Disorders (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.

Secondary Endpoints:

For OUD:

Drug-Taking Behavior (≥ 80% abstinent between Week 5 to Week 12), treatment duration (days in treatment), and scores on the Subjective Opiate Withdrawal Scale (SOWS), the Clinical Opiate Withdrawal Scale (COWS), and the Opioid Craving Visual Analog Scale (OC-VAS) are secondary efficacy endpoints for monitoring the effects of treatment on symptoms on OUD.

For PTSD:

The secondary efficacy endpoints for monitoring the effects of treatment on core symptoms of PTSD are CAPS-5 change score (between screening and Week 12).

Population:

120 veteran participants will be recruited from within the MEDVAMC. The study population will consist of veterans diagnosed with OUD and potential or provisional PTSD who are seeking treatment.

Phase:

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

Duration:

Enrollment period of 24 months. Participant duration is 18 weeks (consisting of 4 weeks screening, a 12-week treatment period, and a 2-week follow-up).

Being tested
Lofexidine, Placebo oral tablet
Keywords
Opioid Use Disorder (OUD), Opioid, Opioid Use, Post Traumatic Stress Disorder (PTSD), Veteran
Medical subject headings
Stress Disorders, Post-Traumatic, Opioid-Related Disorders

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • LofexidineDrug

    Also called LFX

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

  • Placebo oral tabletDrug

    Also called PLB

    Placebo

Study groups in NCT04360681
Study groupRoleWhat they receive
Lofexidine (LFX)ExperimentalLFX 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.
Receives: Drug: Lofexidine
Placebo (PLB)Placebo comparatorA placebo drug will be employed as the comparison group to active study drug.
Receives: Drug: Placebo oral tablet

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 12 weeks

  2. 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.

    Measured: 12 weeks

Secondary outcomes (2)

  1. Opioid Withdrawal

    Scores on opiate withdrawal scales, including the Subjective Opiate Withdrawal Scale (SOWS) and the Clinical Opiate Withdrawal Scale (COWS), are secondary efficacy endpoints. A lower total SOWS score (range: 0-64) indicates a more favorable clinical outcome. A COWS score of 5 to 12 is considered mild, 13 to 24 is moderate, 25 to 36 is moderately severe, and a score exceeding 36 is considered severe withdrawal. These scales are completed

    Measured: 12 weeks

  2. PTSD Symptoms

    CAPS-5 change score (between screening and Week 12) is a key secondary efficacy endpoint for PTSD

    Measured: 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Apr 2020
  2. Study start9 Mar 2021
  3. Primary completion15 Dec 2025
  4. Study completion29 Jan 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This is a Phase 2 randomized, double-blind, placebo-controlled, single-site, parallel groups, 12-week treatment study
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
84 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04360681
Sponsor's protocol ID
AS170014-A6
Status last verified
May 2026
First submitted
16 Apr 2020
Last updated
8 May 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Congressionally Directed Medical Research Programs (CDMRP) has a policy to share and make available to the public the results and accomplishments of the activities that it funds. The Pharmacotherapies for Alcohol and Substance Abuse (PASA) Consortium plans to share de-identified data after final publication in a government-supported data repository

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Lofexidine in people with Post Traumatic Stress Disorder and Opioid-use Disorder, run by Pharmacotherapies for Alcohol and Substance Use Disorders Alliance at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 May 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Opioid Use (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04360681.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 May 2026.

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