Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05204576 |
| Other study ID # |
2000026276 |
| Secondary ID |
1R61AT010619-014 |
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
July 15, 2022 |
| Est. completion date |
June 2025 |
Study information
| Verified date |
April 2024 |
| Source |
Yale University |
| Contact |
TBN |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The investigators plan to develop and pilot test an integrated, web-based cognitive
behavioral approach and then conduct a randomized clinical trial evaluating its efficacy
relative to standard care in a large and diverse sample of individuals with chronic pain
treated with buprenorphine or methadone. The new program will retain key components of Dr.
Carroll's computer-based training for cognitive-behavioral therapy (CBT4CBT), including its
emphasis on teaching cognitive and behavioral coping skills in an engaging way and focus on
the 5 A's of MAT (Adherence, Attendance, Abstinence, Alternate Activities and Accessing
support); it will add components from Dr. Heapy's COPES (Cooperative Pain Education and
Self-Management) intervention (self-management of chronic pain, with daily surveys via text
that monitor pain intensity and interference, physical activity, and skills practice) and
modify existing CBT4CBT modules to address the complex interplay between pain and drug use in
this population, emphasizing the development of generalizable skills. A randomized clinical
trial evaluating CBT4CBT-COPES will be conducted in a diverse sample 160 of individuals
enrolled in agonist treatment (methadone or buprenorphine) who have chronic pain, in a
3-month randomized clinical trial with a 6-month follow-up, comparing it to standard
treatment alone. The primary retention outcome will be adherence with agonist treatment; the
primary pain outcome will be the PROMIS 6-item Pain Interference Short Form.
Description:
Evaluate the efficacy of CBT4CBT-COPES versus standard care (treatment as usual) at 3 months
(primary endpoint) among 160 individuals with OUD and chronic pain enrolled in OAT at the
Liberation clinics. The primary outcome will be adherence to OAT (defined as continuous and
verified enrollment at the 3-month timepoint); the primary pain outcome will be pain
interference as measured by the PROMIS 6-item Pain Interference Short Form. Hypothesis 1a:
Individuals randomized to CBT4CBT-COPES will have greater retention at the 3-month point than
those assigned to standard care. Hypothesis 1b: CBT4CBT-COPES will be associated with greater
reductions in pain interference at the 3-month point.
2. Conduct a 6-month follow-up to evaluate the durability of effects on the primary outcomes.
The investigators hypothesizes CBT4CBT-COPES will be associated with greater adherence and
reduced pain interference compared with standard care at the 3 and 6-month follow-ups (6 and
9 months post randomization).
Procedures Initial Screening by Project Manager or Research Assistant: Individuals enrolled
in the buprenorphine or methadone programs at Liberation will be informed of the study via
flyers, group meetings, or their clinicians. Individuals who indicate they are interested in
hearing more about the study will be offered a meeting with the research staff. At the first
interview, the research staff will provide an overview of the study and obtain written
informed consent. The investigators use a multiple-choice test to assess participants'
comprehension of the protocol, with ample time to review questions to assure understanding of
the protocol, consent, and treatments offered. After determination of eligibility and
informed consent, pre-treatment assessments will be completed. Randomization will occur as
soon as participants have achieved a therapeutic dose of buprenorphine or methadone.
Urn randomization. To increase the likelihood that treatment groups are balanced with respect
to demographic variables (gender, race), as well as likely prognostic variables (severity of
opioid use disorder as moderate or severe via DSM-5 OUD symptom count, initial opioid
experience of heroin versus prescription opioids, buprenorphine versus methadone treatment,
pain severity (mild, moderate vs. severe) as operationalized by NRS average weekly pain
rating). Participants will be assigned to treatment conditions through urn randomization
using a Microsoft Access program developed and implemented successfully in multiple previous
trials.
Treatment phase: Treatment conditions are described in detail below. Study treatments will
last 12 weeks. During the treatment phase, all participants will meet weekly with the
research assistant for completion of self-report and interview assessments preferably
in-person, but with the option of virtual meetings. Breath and urine sample collection will
be taken by the research assistant at this time.
Clinical deterioration: The investigators will closely monitor participant treatment response
and safety in all conditions through weekly assessment sessions that will include brief
assessment of psychiatric status. Although in the investigators experience this is a very
rare event, including during computer-assisted therapy, participants who show significant
deterioration (e.g., increased drug/alcohol use or psychiatric symptoms that cannot be
managed within the protocol, including significant suicidal or homicidal ideation) will be
regarded as symptomatic failures, withdrawn from the treatment arm of the study, and referred
for appropriate treatment (usually inpatient care). The project psychiatrist (Dr. Sofuoglu)
will make the final withdrawal determination, using guidelines the investigators have worked
out in previous studies. At the time of withdrawal, endpoint ratings will be made which
include the full termination assessment battery.
Termination and post treatment assessment: At the end of the 12-week treatment period, all
participants will be re-interviewed by the research assistant, who will complete post
treatment ratings. Access to the CBT4CBT-COPES program will be terminated; however,
participants in all conditions will be strongly encouraged to continue in agonist treatment
at Liberation clinics.
Follow-up: Follow-up interviews will be conducted 1, 3, and 6 months after termination (the
investigators find the one-month follow-up strengthens the relationship with the research
staff and results in higher rates of follow-up). Follow-up interviews will include the full
post-treatment battery, including assessment of utilization of other treatments and services.
The investigators will attempt to follow all participants in the intention to treat sample,
regardless of their retention in treatment, using strategies that have been successful in
multiple previous studies. These include: (a) thorough explanation at the initial consent
interview of the importance of follow-ups, (b) requiring that each participant provide at
least 2 verified locators with knowledge of their whereabouts throughout follow-up, (c) use
of multiple sources and locators to track participants, and (d) participant payment of $35
for each completed follow-up interview, with additional incentives for completing interviews
on time and for completing consecutive follow-up interviews. Using these procedures, the
investigators current rate of follow-up approaches 90-95% across studies for
intention-to-treat analyses. For those who drop-out and cannot be re-engaged, the
investigators will ask participants to complete a brief survey exploring their reasons for
dropping out.
Rationale for study length: Given the 3-year limit for the R33 phase, in order to recruit a
sample size for adequate power, the investigators decided to evaluate primary outcomes at 3
months, with an additional 6 months of follow-up (9-month total study period). This will
allow the investigators to evaluate retention in OAT at the 6-month point. This should be
adequate, as the bulk of attrition in OAT tends to occur earlier in treatment. Three months
will allow for adequate exposure to the CBT4CBT-IMPACT intervention for those assigned to
that condition; the additional 6 months of follow-up will allow evaluation of durability of
treatment effects, and importantly, pain symptoms and use of health services for an adequate
period.
Rationale for design: While a 3- or 4-cell design would allow for the integrated
CBT4CBT-IMPACT intervention to be tested against either CBT4CBT or IMPACT alone, because of
the 3 year time limit for the R33 phase and the emphasis on adequate power for the trial, the
investigators decided the two-cell design would allow the investigators to determine if the
integrated approach improves adherence and pain outcomes over standard OAT treatment in an
adequately powered trial. If determined to be effective here, subsequent studies could
evaluate the efficacy of the integrated approach relative to CBT4CBT or IMPACT alone, which
would also allow for detailed evaluation of mechanism. Recruiting from a large specialty
program will allow the investigators to recruit adequate numbers of both buprenorphine and
methadone patients and hence enable some comparisons; this would be difficult in most primary
care clinics. The Liberation evening clinic is similar to many office-based buprenorphine
settings.
Treatments Standard care treatment as usual (TAU): Participants randomized to this condition
will receive treatment-as-usual for the buprenorphine and methadone programs at Liberation
Clinics, which includes regular medication management by the clinic physician, regular
individual and group sessions and access to other services as needed. The investigators have
worked closely with Liberation Clinics for over 20 years; the investigators selected this
program because they are high-quality, well-managed programs which have supported multiple
clinical research programs (including both Yale and CTN multi-site randomized trials of
behavioral and pharmacologic approaches. All patients will also have access to counseling
delivered onsite by highly experienced masters-level counselors employed at Liberation
Clinics. Methadone and buprenorphine adherence will be monitored closely (via Timeline
FollowBack as well as daily methadone visits, verification of buprenorphine prescriptions and
counts, and evidence of buprenorphine/methadone in weekly urine toxicology screens).
Utilization of all services (including counseling, medical care, ED visits, legal services,
pharmacological and non-pharmacologic treatments for pain, etc.) will be monitored closely
throughout the trial and through follow-up, in all conditions, using the PACC-SAT .
CBT4CBT-IMPACT. Participants assigned to this condition will receive standard agonist
treatment but also receive access to CBT4CBT-IMPACT. At the time of randomization,
participants will be given a username and asked to select a password to access the
CBT4CBT-IMPACT website. The research staff will work with each participant to determine when,
where, and how they will access the program (although participants will be free to access the
program in a private area at the clinic as well). For the first session, research staff will
guide the patient through the program to assure they are comfortable using the program and
answer any questions they might have. Participants will be asked to spend at least one hour
per week working with the program, either at the clinic or outside of the clinic (e.g. at
their home). Participants will be asked to complete all 9 modules over the course of the
12-week study treatment period, repeating any modules, or sections, as they desire. At the
start of each session, the study staff reviews the modules that the user has completed and
directs users to either complete modules they have started or access new ones. The program
tracks, for each participant, time logged onto the program, modules accessed, session
progress, completion of practice exercises, and learning of CBT principles through multiple
choice tests at the end of each module. Participants randomized to this condition will also
be provided with a pocket pedometer to facilitate their participation in the walking portion
of the treatment. Study staff will measure each participant's stride length, adjust the
pedometer stride length setting accordingly, and provide a brief demonstration of pedometer
use. Pedometers will record only steps.
Daily texts with a link for survey: Following randomization to CBT4CBT-IMPACT, participants
will undergo daily assessment via text of pain intensity, pain interference,
pedometer-measured step counts, sleep quality, sleep duration, and craving for seven days to
establish a baseline of function for the purposes of treatment and providing regular feedback
using questions derived from validated measures and used in our prior trials. After the
baseline period, participants will continue to receive daily texts for the duration of the
treatment. During treatment, two additional questions regarding practice of the treatment
skills and progress toward the weekly meaningful activity goal will be included.
Patient-reported data collected on the daily texts with link to a survey will form the basis
for regular feedback, which will be tracked and viewed in graphical form from the patient
dashboard of the program. Participants will receive texts with a link to a survey each day at
a time pre-selected by the patient. Surveys will be no longer than 2 minutes in duration.
