Optimal Treatment of Veterans With PTSD and Comorbid OUD

NCT03605342 | Terminated Phase 2 Results DMC

• 1 other identifier: MHBB-010-17F
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 2

Brief Summary

The objective of this study is to test a standard psychotherapy for PTSD in Veterans who also suffer from Opiate Use Disorder (OUD). Specifically, this study will test whether Cognitive Processing Therapy (CPT)-C is more effective in treating PTSD, compared to a control group (Individual Drug Counseling (IDC); which approximates treatment as usual), among Veterans with PTSD and comorbid OUD who are maintained on buprenorphine. The study has three phases. In Phase I: induction to buprenorphine/naloxone (BUP/NLX) maintenance. Phase II: treatment. During this phase participants will be randomly assigned to CPT-C or IDC for 12 weeks. They will be seen weekly for psychotherapy and also regularly (weekly, then biweekly, then monthly) for buprenorphine management, symptom evaluation, and medication refill. After completing treatment participants will be referred to a buprenorphine clinic for ongoing care. Phase III: follow-up. Approximately 160 male and female Veterans (18-65 years old) with PTSD and comorbid opiate use disorder (OUD) will be enrolled in this study. Recruitment will be through VA clinics, word-of-mouth, referrals from area programs and by advertisement. Veterans who are interested will complete a brief pre-screening and detailed in-person screening. After completing the screening process, all eligible participants will be started on buprenorphine maintenance and once withdrawal symptoms are stabilized, participants will be randomly assigned to 1 of 2 conditions (CPT-C or IDC) for 12 weeks. Veterans who are already on BUP/NLX will be allowed to participate and will start at Phase II of the study, after completing the screening.

Conditions

Post-Traumatic Stress Disorders; Opiate Use Disorder

Keywords

PTSD; Opiate Use Disorder

Outcome Measures

Primary Outcomes (4)

• Clinician Administered PTSD Scale (CAPS-5)

  Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (CAPS-5) is a structured diagnostic interview. The scale also assesses social and occupational functioning, dissociation symptoms, and the validity of symptom reports. The CAPS-5 uses a single 5-point ordinal rating scale to measure symptom severity. Symptom severity ratings combine information about symptom frequency and intensity obtained by the interviewer. The CAPS-5 requires approximately 40 minutes to administer. Scores can range from 0 (minimum score) - 80 (maximum score) with higher scores indicating greater severity. (0-19=Asymptomatic/few symptoms very mild PTSD, 20-39=Sub-threshold/mild PTSD, 40-59=Threshold PTSD/moderate PTSD, 60-79=Severe PTSD, 80=Extreme PTSD)

  Baseline

• PTSD Checklist - Military Version (PCL-5) Total Score

  PCL-5 will be used to collect information on PTSD symptoms. The PCL-5 is a 20-item self-report measure, selected for its dimensional sensitivity, with higher scores reflecting greater PTSD severity. Scoring is based on how much the patient has been bothered by the symptoms on a scale from "0 = not at all" to "4 = extremely." Items are summed to provide a total severity score (range 0-80). PCL-5 score between 31-33 is indicative of PTSD.

  Baseline

• Clinician Administered PTSD Scale (CAPS-5)

  Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (CAPS-5) is a structured diagnostic interview. The scale also assesses social and occupational functioning, dissociation symptoms, and the validity of symptom reports. The CAPS-5 uses a single 5-point ordinal rating scale to measure symptom severity. Symptom severity ratings combine information about symptom frequency and intensity obtained by the interviewer. The CAPS-5 requires approximately 40 minutes to administer. Scores can range from 0 (minimum score) - 80 (maximum score) with higher scores indicating greater severity. (0-19=Asymptomatic/few symptoms very mild PTSD, 20-39=Sub-threshold/mild PTSD, 40-59=Threshold PTSD/moderate PTSD, 60-79=Severe PTSD, 80=Extreme PTSD)

  Week 12

• PTSD Checklist - Military Version (PCL-5) Total Score

  PCL-5 will be used to collect information on PTSD symptoms. The PCL-5 is a 20-item self-report measure, selected for its dimensional sensitivity, with higher scores reflecting greater PTSD severity. Scoring is based on how much the patient has been bothered by the symptoms on a scale from "0 = not at all" to "4 = extremely." Items are summed to provide a total severity score (range 0-80). PCL-5 score between 31-33 is indicative of PTSD.

  Week 12

Study Arms (2)

Buprenorphine + CPT-C

ACTIVE COMPARATOR

Buprenorphine induction and stabilization for all participants (x1 week). Participants will be started at a dose of 2mg/0.5 mg BUP/NLX and this dose will be increased as needed for stabilization of opioid withdrawal symptoms up to 24 mg per day, then CPT-C for 12 weeks.

Drug: Buprenorphine; Behavioral: Cognitive Processing Therapy (CPT)

Buprenorphine + IDC

ACTIVE COMPARATOR

Buprenorphine induction and stabilization for all participants (x1 week). Participants will be started at a dose of 2mg/0.5 mg BUP/NLX and this dose will be increased as needed for stabilization of opioid withdrawal symptoms up to 24 mg per day, then IDC for 12 weeks

Drug: Buprenorphine; Behavioral: Individual Drug Counseling (IDC)

Interventions

Buprenorphine DRUG

Participants will be started at a dose of 2mg/0.5 mg BUP/NLX and this dose will be increased as needed for stabilization of opioid withdrawal symptoms up to 24 mg per day, which is standard practice.

Buprenorphine + CPT-C; Buprenorphine + IDC

Cognitive Processing Therapy (CPT) BEHAVIORAL

CPT-C is a manualized, 12-session 1:1 cognitive therapy that has been designed for patients with PTSD. In this study the sessions will be conducted weekly. CPT-C uses Socratic questioning targeting distorted cognitions such as self-blame, hindsight bias, and other guilt cognitions. CPT-C is focused on the cognitive components of the therapy without exposure.

Buprenorphine + CPT-C

Individual Drug Counseling (IDC) BEHAVIORAL

IDC will serve as the control group. The current standard of treatment for Veterans entering buprenorphine maintenance is to do drug counseling. Standard counseling is the primary means to achieve goals. IDC uses a semi-structured, time-limited addictions-counseling model in a 1:1 setting. The IDC manual provides an organized, concise version of what is currently practiced by most addiction counselors.

Buprenorphine + IDC

Eligibility Criteria

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

You may qualify if:

• Current diagnosis of PTSD as determined by an independent evaluator assessment using CAPS-5.
• Opioid Use Disorder diagnosed by Structured Clinical Interview for DSM-5 (SCID-V)
• To meet entry criteria for buprenorphine treatment:
• will also have documented prior treatment for opioid use disorder
• history of opioid withdrawal or signs of opiate withdrawal as evidenced by a Clinical Opiate Withdrawal Scale (COWS) score of 7 or greater
• a positive urine toxicology for opioids
• Medically and neurologically healthy on the basis of:
• history
• physical examination
• EKG
• screening blood tests (CBC w/ differential, Thyroid-stimulating hormone (TSH), Free-T4, aspartate aminotransferase (AST), alanine aminotransferase (ALAT), Gamma-glutamyl transferase (GGT), blood urea nitrogen (BUN), creatinine, calcium, phosphorous, magnesium, total protein, albumin, electrolytes, urinalysis, urine toxicology, beta-HCG)
• For women, negative pregnancy test and use of acceptable method of contraception

You may not qualify if:

• Females who are pregnant or lactating
• Veterans with a current unstable medical condition such as:
• neurological
• cardiovascular
• endocrine
• renal
• liver
• or thyroid pathology (e.g. abnormal BUN and creatinine, and unmanaged hypertension with BP \> 200/120) which in the opinion of the physician would preclude the patient from fully cooperating or be of potential harm during the course of the study
• Veterans who meet current criteria for the following diagnoses (bipolar disorders, schizophrenia and schizophrenia spectrum and psychotic disorders) as determined by the SCID-V
• Veterans who have significant current suicidal or homicidal risks necessitating a higher level of care
• Those with known allergy or intolerance to buprenorphine

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (2)

VA Connecticut Healthcare System West Haven Campus, West Haven, CT

West Haven, Connecticut, 06516-2770, United States

Location

Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA

Bedford, Massachusetts, 01730, United States

Location

Related Publications (1)

• Petrakis IL, Meshberg-Cohen S, Nich C, Kelly MM, Claudio T, Jane JS, Pisani E, Ralevski E. Cognitive processing therapy (CPT) versus individual drug counseling (IDC) for PTSD for veterans with opioid use disorder maintained on buprenorphine. Am J Addict. 2024 Sep;33(5):525-533. doi: 10.1111/ajad.13557. Epub 2024 Apr 16.

  PMID: 38624259 RESULT

MeSH Terms

Conditions

Stress Disorders, Post-Traumatic

Interventions

Buprenorphine

Condition Hierarchy (Ancestors)

Stress Disorders, Traumatic; Trauma and Stressor Related Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Results Point of Contact

• Title: Dr Ismene Petrakis
• Organization: VA Connecticut Healthcare System

Ismene.Petrakis@va.gov

203-932-5711

Study Officials

• Ismene L. Petrakis, MD

  VA Connecticut Healthcare System West Haven Campus, West Haven, CT

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: To fully assess and appreciate complex symptomatology in this patient population, assessments were selected to have both relevance to the investigators' study of PTSD and comorbid OUD. Assessments will be done by an Independent Evaluator (IE) blind to treatment group.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Model Details: This study is a 14-week, open-label randomization: 1) buprenorphine (BUP) + CPT-C vs (2) BUP + IDC. Phase I: buprenorphine induction and stabilization for all participants. Participants starting dose 2mg/0.5 mg BUP/NLX this will increase as needed up to 24 mg per day. Phase II: randomization to CPT vs. IDC (x12 weeks). Phase III: Subjects will be referred to one of the buprenorphine clinics and will be referred for ongoing treatment for PTSD if they choose, including the option for CPT-C for those who did not receive this during the study. Participants will be seen on a daily basis (excluding weekends) for the initial 5-7 day induction. Once subjects are on maintenance dose of BUP/NLX, they will be seen weekly by study Registered Nurse (RN) for the first 4 weeks, biweekly for a month then monthly for symptom evaluation, and medication refill.

Study Record Dates

• First Submitted: June 29, 2018
• First Posted: July 30, 2018
• Study Start: October 1, 2018
• Primary Completion: April 14, 2023
• Study Completion: April 14, 2023
• Last Updated: August 19, 2024
• Results First Posted: August 19, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)