Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05552040 |
| Other study ID # |
IRB-20-1064 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 4, 2018 |
| Est. completion date |
May 1, 2020 |
Study information
| Verified date |
September 2022 |
| Source |
Carilion Clinic |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This investigation involves a partially randomized clinical trial examining the effectiveness
of combining buprenorphine/naloxone MAT with START NOW, a skills-based psychosocial
intervention modified specifically for the ambulatory substance use disorder (SUD) patient
population. START NOW is an integrated evidence-informed model based on an adapted form of
dialectical behavior therapy (DBT), a type of cognitive behavior therapy (CBT) with promising
indications for treating SUD as it targets impulsive and self-destructive behaviors.
Furthermore, START NOW combines CBT, the most widely used evidence-based psychosocial
intervention for treating mental disorders, with motivational interviewing, which in clinical
trials has been shown to be an effective technique for engaging patients with SUD. In
addition to tracking clinical outcomes such as abstinence rates through weekly urine drug
screens, this investigation will use: clinician assessments of disease severity,
researcher-evaluated tests of delayed discounting (DD) and demand tasks, and self-report
surveys assessing impulsivity, aggression, interpersonal skills, and other measures to
capture the patients' sense of progress in treatment in regards to their substance use,
health, lifestyle, and community. By using DD and functional magnetic resonance imaging
(fMRI), the identification of the neural correlates of START NOW treatment response will
begin to elucidate the mechanisms of START NOW's effects and more. This investigation's
outcome measures may not only compare the effectiveness between START NOW and
treatment-as-usual (TAU), but also provide a more realistic, holistic view of patients and
their well-being throughout the recovery process.
DD will be performed by both START NOW group members and TAU group members at their group
therapy meetings as per protocol. Additionally, START NOW group members randomized and
consented to have an fMRI will also perform DD before the scan is initiated.
Description:
There is an unmet need for implementing a clinically superior behavioral therapy intervention
for medication-assisted treatment of opioid use disorder.
One strategy for fighting the opioid epidemic is to improve treatment and detoxification
programs. In the United States, the Drug Addiction Treatment Act of 2000 requires that
physicians combine medication-assisted treatment (MAT) with a behavioral intervention.
However, there is no clear evidence regarding what form of therapy is most effective when
coupled with MAT for opioid use disorder (OUD) management.
This investigation will explore the impact of a novel skills-based psychosocial intervention
called START NOW, which has been modified for the substance use disorder (SUD) patient
population. The promising therapeutic potential of START NOW is evident in the growing data
affirming the program's utility and the psychosocial techniques with substantial supportive
evidence incorporated into the program. This investigation will attempt to prove through a
number of clinical and behavioral parameters how START NOW with MAT may be an effective
treatment program for patients undergoing OUD treatment.
START NOW is an evidence-informed psychotherapy composed of a total of
32-skills-based-sessions, originally designed for inmates in correctional systems. A previous
study of incarcerated individuals found that for each additional session of START NOW
completed, a 5% reduction in the incident rate of disciplinary reports was noted. In fact,
individuals with a higher overall security risk score also had a greater reduction in the
number of disciplinary reports with more sessions attended, suggesting that START NOW is an
effective behavioral intervention for those who need it most. A follow-up study on these same
participants concluded that START NOW appears to have a beneficial clinical effect with each
session completed being associated with a 5% decrease in subsequent psychiatric hospital
days. Evidence continues to build in support for START NOW as a behavioral intervention as
its implementation continues to grow. For example, START NOW is currently being used in
correctional facilities in more than 10 states in the US. Using a randomized, controlled
trial in Europe, investigators are evaluating START NOW's ability to enhance psychosocial
adjustment and well-being and to reduce oppositional and aggressive behavior in 128
institutionalized female adolescents diagnosed with oppositional defiant disorder and/or
conduct disorder.
Investigators hypothesize that OUD patients who complete START NOW group therapy will show a
statistically greater reduction in impulsivity, delay discounting, and illicit drug use
compared to the OUD patients who complete the treatment-as-usual (TAU) because of START NOW's
integrated model of care. For example, START NOW combines CBT, the most widely used
evidence-based psychosocial intervention for treating mental disorders, with motivational
interviewing, which in clinical trials has been shown to be an effective conjunction
intervention for SUD. START NOW exercises psychosocial techniques similar to dialectical
behavior therapy (DBT), a type of cognitive behavior therapy (CBT) with promising indications
for treating SUD because it targets impulsive and self-destructive behaviors. A currently
unpublished pilot study using START NOW in an office-based outpatient treatment setting with
OUD yielded patient satisfaction data and detailed feedback; this data is being used to guide
the modification process of START NOW's materials and delivery so that START NOW is more
culturally sensitive and appropriate for the SUD patient population. This proposed
investigation will use the revised START NOW participant workbooks and real-life exercises
adapted specifically for SUD.
Investigators believe that START NOW possesses many components that make it a particularly
useful behavioral intervention for SUD. For example, the program is divided into four units,
and Unit 1, while teaching focusing skills and functional analysis of behavior skills, tries
to teach individuals how to develop self-control, cope with stressors, and become ready for
change. Unit 2 focuses on understanding and coping with feelings and emotions. Unit 3 aims to
teach individuals how to build positive relationships with others. Finally, Unit 4 focuses on
setting and reaching personal goals. Investigators hypothesize that using START NOW's
manual-guided approach will confer improved executive functioning skills and decreased
delayed discounting, which will ultimately yield better clinical outcomes. This will be the
first investigation evaluating an adapted START NOW for treating OUD with
buprenorphine/naloxone MAT in the outpatient setting. The study aims to provide clinical
utility for healthcare professionals in the field of addiction medicine and contributions to
the understanding of addiction biology.
Delayed discounting may be a useful biomarker for tracking and predicting clinical outcomes
for patients undergoing rehabilitation Delayed discounting (DD) is a behavioral marker for
impulsive decision-making and devaluation of delayed rewards. This investigation will use
delayed discounting as an objective measure of cognitive executive functioning of its study
participants before, during, and after treatment. Furthermore, we will compare DD values to
clinical outcomes, clinician assessments, and self-report assessments in order to see if
there is a correlation between all of these measures.
Opiate addiction has consistently been found to correlate with delay discounting, especially
during periods of active addiction and especially amongst intravenous heroin users. However,
methadone treatment, even when it resulted in the avoidance of relapse or other drug use, did
not significantly improve delay discounting, when compared to the treatment condition in
which participants continued to abuse substances. The authors of this study suggest that this
may be due to patients receiving effective drug treatment that does not involve prolonged
substitution therapy may be forced to develop better self-control skills to remain abstinent.
In a comparison between buprenorphine and methadone, a 2012 study found buprenorphine has a
number of advantages over methadone for use in MAT. While methadone is a full agonist of
opioid receptors, buprenorphine is a weak partial agonist, especially at the mμ opioid
receptor, thereby causing less analgesia and euphoria.
Investigators hypothesize that methadone, as a full agonist more prone to inducing euphoria
and thereby enabling drug abuse, may prevent the improvement in cognitive executive functions
theorized to be impaired by substance dependence. Moreover, the unique pharmacokinetics and
pharmacodynamics profiles of buprenorphine may allow for more stable disease control, reduced
harmful behavior, and thus improvements in cognitive executive functions (namely DD) for
individuals undergoing concomitant buprenorphine MAT and an effective psychosocial
intervention such as START NOW. Furthermore, previous studies found that DD decreases in
individuals completing treatment for opioid dependence with buprenorphine MAT, but they
failed to find any relationship between DD measures and abstinence outcomes.
While DD might be a stable trait in some individuals, a technology of behavior that
manipulates DD may not only impact DD but also reduce the impulsive choices that comprise
behavioral patterns of addiction and poor health-decision-making. Studies have successfully
shown reduced delay discounting (DD) when targeting cognitive skills such as learning to
activate one's working memory for longer periods. The clinical trial proposed by this
investigation not only utilizes MAT and START NOW as a unique approach for not only treating
OUD and developing effective clinical practices, but also aims to enhance the understanding
of DD in addiction treatment outcomes. Showing a correlation between DD and opioid addiction
may enable clinicians and researchers alike with the ability to predict treatment success and
to use DD as a biomarker for OUD disease regression or relapse.
DD will be measured in both groups during the appointed time at the designated group
sessions. Those in the START NOW group that have been randomized to have the fMRI will also
perform DD before their fMRI scan.
Neural correlates will be studied from before and after the START NOW treatment begins.
Neural correlates in the TAU group will be not studied. The identification of the neural
correlates of START NOW treatment response may lead to a number of potential future
directions. First, understanding who is most likely to respond to treatment may help target
treatment efforts. Second, this information will help elucidate the mechanisms of START NOW
effects, allowing for refining and further development of the treatment approach. Third,
future efforts could use knowledge gained in this proposal to directly target behavior change
with techniques such as transcranial magnetic stimulation or real-time fMRI biofeedback. All
of the information obtained through this investigation's outcome measures may help in the
development of a superior behavioral intervention for OUD and improve our understanding of
addiction biology.
For participants in the START NOW group, those that are eligible and interested will be
randomized to have an fMRI or not. Only 20 participants will complete the fMRI. These
participants will perform delayed discounting tasks in fMRI sessions before and after
behavioral intervention. Investigators expect the neural correlates of delayed discounting to
predict START NOW treatment success. Depending on the results, the fMRI component of this
investigation may elucidate the mechanisms of START NOW's effects, help create a model for
predicting treatment success, or provide information on how to better target behavior change.
Neural correlates will only be studied in the START NOW group, comparing before and after the
treatment begins.
Beyond capturing a participant's drug use and clinical disease course, this study aims to
capture participants' personal satisfaction with one's livelihood and other measures to
effectively compare START NOW with TAU. Moreover, investigators hypothesize that in the
best-case scenario, individuals who maintain their sobriety, regardless of the behavioral
treatment intervention they receive, will show improvements in other aspects of their lives.
For example, individuals who remain sober throughout treatment (clean urine drug screens)
will also show: decrease disease severity (CGI-S), increased disease improvement (CGI-I),
reduced impulsivity (BIS), decreased aggression (AGQ), and fewer interpersonal problems
(IIP). With all of these measures, investigators hope to offer a more compassionate,
comprehensive view-one that extends beyond the disease and diagnosis-of the whole patient.
Data Analysis For Specific Aim 1, the differences between START NOW and TAU utilizing an
intent-to-treat model with a regression statistical approach will be evaluated. The specific
regression model will be determined by the distribution of the data. For Specific Aim 2 and
3, self-assessment by the participants between START NOW and TAU will be compared in the
stated domains using an analysis of variance model (ANOVA). For Specific Aim 4, neural
correlates associated with delay discounting task performance will be compared between
groups. For Specific Aim 5, variance / co-variance matrixes of SNAP compared to the BIS, AGQ,
and IPP will be looked at to determine the factor structure and correlation between the
instruments.
Investigators hypothesize that activation of valuation networks (e.g., dopaminergic networks
connecting midbrain to frontal cortices) will predict and change in response to START NOW
treatment success.
