RECRUITING

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

Conditions

Post Traumatic Stress Disorder Opioid-use Disorder Opioid Use Disorder (OUD)Opioid Opioid Use Post Traumatic Stress Disorder (PTSD)Veteran

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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 .

Official Title

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

Quick Facts

Study Start:2021-03-09

Study Completion:2025-09-28

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04360681

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 70 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
1. 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). 2. 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. 3. Have a positive urine toxicology screen for BUP. 4. 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). 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. 6. Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation within 3 months of study entry.	1. DSM-5 criteria for substance use disorders (SUDs) other than OUD, nicotine, or cannabis, or stimulants \[assessed by UDS and the Mini-International Neuropsychiatric Interview (MINI)\]. 2. Self-reported use of methadone in the last 14 days. 3. Be undergoing significant opioid withdrawal, as assessed by the COWS (defined as \>12 on the COWS). 4. 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). 5. 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. 6. Use of any of the following medications within 30 days prior to enrollment (self-report on Prior/Concomitant Medications (Meds) form): 1. Benzodiazepines, barbiturates, or other CNS depressants 2. Methadone or any other prescription analgesics, except BUP or BUP/naloxone 3. Opioid antagonists such as naltrexone, except naloxone in combination with BUP 4. Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives 5. Drugs that have been associated with QT prolongation, including: 1. Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, etc. 2. Macrolides: erythromycin, roxithromycin, azithromycin, clarithromycin, etc. 3. Antifungals: ketoconazole, itraconazole, etc. iii. Antipsychotics: haloperidol, thioridazine, ziprasidone, clozapine, quetiapine\, risperidone\, olanzapine, etc. * The following medications will be permissible at the discretion of the study physician: 1. Bupropion a. Allowable dosage of up to 150mg daily (this is well below the therapeutic dose for depression, but is given for smoking cessation) 2. Quetiapine 3. Risperidone 1. 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): 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: 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

Inclusion Criteria

Exclusion Criteria

1. 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).
2. 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.
3. Have a positive urine toxicology screen for BUP.
4. 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).
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.
6. Have a medical history and physical examination demonstrating no clinically significant contraindications for study participation within 3 months of study entry.

1. DSM-5 criteria for substance use disorders (SUDs) other than OUD, nicotine, or cannabis, or stimulants \[assessed by UDS and the Mini-International Neuropsychiatric Interview (MINI)\].
2. Self-reported use of methadone in the last 14 days.
3. Be undergoing significant opioid withdrawal, as assessed by the COWS (defined as \>12 on the COWS).
4. 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).
5. 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.
6. Use of any of the following medications within 30 days prior to enrollment (self-report on Prior/Concomitant Medications (Meds) form):
1. Benzodiazepines, barbiturates, or other CNS depressants
2. Methadone or any other prescription analgesics, except BUP or BUP/naloxone
3. Opioid antagonists such as naltrexone, except naloxone in combination with BUP
4. Tricyclic antidepressants, which may reduce the efficacy of imidazoline derivatives
5. Drugs that have been associated with QT prolongation, including:
1. Fluoroquinolones: ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, etc.
2. Macrolides: erythromycin, roxithromycin, azithromycin, clarithromycin, etc.
3. Antifungals: ketoconazole, itraconazole, etc. iii. Antipsychotics: haloperidol, thioridazine, ziprasidone, clozapine, quetiapine\*, risperidone\*, olanzapine, etc.
* The following medications will be permissible at the discretion of the study physician:
1. Bupropion a. Allowable dosage of up to 150mg daily (this is well below the therapeutic dose for depression, but is given for smoking cessation)
2. Quetiapine
3. Risperidone
1. 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):
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:
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

Contacts and Locations

Study Contact

Adetola Vaughan

CONTACT

713-794-8912

adetola.vaughan@va.gov

Christopher D Verrico, PhD

CONTACT

713-791-1414

verrico@bcm.edu

Principal Investigator

Christopher D. Verrico, PhD

PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Thomas R Kosten, MD

PRINCIPAL_INVESTIGATOR

Baylor College of Medicine

Study Locations (Sites)

Michael E. DeBakey Veterans Affairs Medical Center

Houston, Texas, 77030

United States

South Texas Veterans Health Care System

San Antonio, Texas, 78229

United States

Collaborators and Investigators

Sponsor: Pharmacotherapies for Alcohol and Substance Use Disorders Alliance

Christopher D. Verrico, PhD, PRINCIPAL_INVESTIGATOR, Baylor College of Medicine
Thomas R Kosten, MD, PRINCIPAL_INVESTIGATOR, Baylor College of Medicine

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-03-09

Study Completion Date2025-09-28

Study Record Updates

Study Start Date2021-03-09

Study Completion Date2025-09-28

Terms related to this study

Keywords Provided by Researchers

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

Additional Relevant MeSH Terms

Post Traumatic Stress Disorder
Opioid-use Disorder