Optimal Treatment of Veterans With PTSD and Comorbid OUD

The purpose of this study is to test whether Cognitive Processing Therapy (CPT-C) is more
effective than Individual Drug Counseling (IDC), which is standard counseling, for the
treatment of PTSD among Veterans with PTSD and comorbid opioid use disorder who are also
maintained on buprenorphine. The investigators propose to conduct a randomized, controlled
trial and Veterans (n=160) diagnosed with PTSD and comorbid OUD will be randomized to one of
2 groups: (a) buprenorphine and CPT-C or (b) buprenorphine and IDC (treatment as usual).

Primary Aim 1:.To test whether CPT-C is more effective than IDC in treating symptoms of PTSD
among Veterans with OUD maintained on buprenorphine. PTSD symptoms will be measured using the
PTSD Checklist - Military version (PCL-5), and confirmed by the Clinician Administered PTSD
Scale using the DSM-5 criteria (CAPS-5).

Secondary Aim 1: To test whether CPT-C is more effective than IDC in reducing opioid use
among Veterans with PTSD and comorbid OUD maintained on buprenorphine. Opioid use will be
measured using the Timeline Follow-back (TLFB) and confirmed by urine toxicology results.

Exploratory Aims: To examine if treatment groups differ in 1) retention, measured by days in
treatment, 2) psychosocial functioning, measured by the Veterans RAND 12-Item Short Form
Health Survey (VR-12), 3) sleep as measured by the Insomnia Severity Index (ISI), since sleep
disturbance is a hallmark of PTSD and during early abstinence from opioids, and 4) Because of
the high comorbidity between PTSD and chronic pain the investigators will explore this
relationship and will measure pain intensity (measured by the Numeric Rating Scale (NRS), and
functional impairment using the PROMIS-29 (Patient-Reported Outcomes Measurement Information
System) longitudinally over the course of treatment. Follow up will be conducted 1 and 3
months after completion of the study to evaluate durability of effect on PTSD symptoms
(measured as changes in PTSD symptoms), opioid use and treatment utilization.

This study will be a randomized, open-label clinical trial. 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 (including: consent, lab
work, interview with clinician including the Structured Clinical Interview for DSM-5 (SCID-5)
and Clinician Administered PTSD Scale for DSM-5 (CAPS-5), medical and psychiatric history).
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. The investigators will use mixed effects models to assess changes
in PTSD symptoms and opiate use over time. Treatments will be used as between-subject factors
and time (in weeks) will be used as a within-subject factor. The primary outcome variables
will be PTSD symptoms as measured by the PCL-5 and CAPS scales. The secondary outcome
variables will be frequency of opiate use generated from the TLFB and confirmed with urine
toxicology results at each medication visit (weeks 1-4, 6,8, 12) and follow-up.

Potential benefits of participation in this study may include a reduction in PTSD symptoms.
However, there is no guarantee or promise that participants will receive any benefit from
participation in this study.

Since 11 September 2001, more than 1.5 million Service Members have deployed more than 2
million times in support of combat operations in Afghanistan and Iraq. One of the signature
injuries from these operations is PTSD. Various reports of the post-deployment health-related
needs estimated that 20% of Veterans returning from deployment will have symptoms of PTSD or
related behavioral health conditions. In addition, the prescription opioid epidemic has
seriously affected Veterans, and Veterans with PTSD are more likely to abuse opioids and to
have high-risk behaviors. Nevertheless, treating comorbid PTSD and OUD has not been
systematically tested. This study proposes to test an evidence based psychotherapy for PTSD
vs. individual drug counseling in Veterans given opioid maintenance treatment who have both
PTSD and OUD.

Inclusion Criteria:

- 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 laboratories (CBC w/ differential, TSH, Free-T4, ASAT, ALAT, GGT, 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

Exclusion Criteria:

- 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