Benzodiazepine Discontinuation in Opioid Agonist Therapy (BZD-OAT)

Distress Tolerance and Benzodiazepine Discontinuation in Opioid Agonist Therapy, Phase 2

The proposed study is a clinical trial, designed to pilot test a Distress Tolerance-Benzodiazepine Discontinuation (DT-BD) intervention for patients on opioid agonist therapy who currently use benzodiazepines. The DT-BD intervention is an adjunctive psychosocial intervention in people seeking to discontinue (BZD) use. The goal of the study is to assess the applicability and feasibility of this intervention through treatment retention and qualitative interviews with four participants who are receiving opioid agonist treatment and who regularly use BZDs.

Study Overview

• Status: Completed
• Conditions: Substance Use Disorders
• Intervention / Treatment: Behavioral: Distress Tolerance - Benzodiazepine Discontinuation (DT-BD); Drug: BZD discontinuation protocol

Detailed Description

This study pilots a 13-week psychosocial intervention paired with a benzodiazepine taper with the aim of assisting individuals receiving OAT discontinue benzodiazepine use. All participants will receive the same benzodiazepine (BZD) discontinuation protocol. The Distress Tolerance-Benzodiazepine Discontinuation (DT-BD) intervention consists of 14 study visits: the first visit consists of the baseline assessment and the first therapy visits, 4 subsequent weekly therapy visits, then a 9-week BZD taper. Some participants may be prescribed non-benzodiazepine medications to treat the underlying conditions for which they were using BZDs [e.g. selective serotonin reuptake inhibitors (SSRI) for anxiety or hypnotics for insomnia]. Data collection will occur starting at the baseline assessment.

• Study Type: Interventional
• Enrollment (Actual): 4
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02118
      • Boston Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age 18 or older
2. Receiving OAT (methadone or buprenorphine) confirmed by toxicology testing for at least 90 days and on a steady dose for 2 consecutive weeks
3. Regular BZD use defined by BZD use 3 or more times per week in past month by self-report and positive urine screen at time of recruitment
4. Provides permission to contact current BZD prescriber if being prescribed BZDs
5. Speaks English
6. Wants to discontinue BZD use

Exclusion Criteria:

1. Pregnant, confirmed by urine pregnancy test
2. Cognitive impairment, as indicated by a score of < 23 on the Mini Mental Status Exam
3. Any past month illicit opioid, barbiturate, z-drug, cocaine, unprescribed amphetamine, or synthetic cannabinoid use determined by self-report or urine drug test
4. Receiving ongoing psychosocial treatment for BZD use disorder
5. Uncontrolled seizure disorder (i.e. seizure in prior 90 days), or past BZD withdrawal seizure
6. Current suicidality or homicidality
7. Current psychotic symptoms

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Distress Tolerance - Benzodiazepine Discontinuation (DT-BD); This psychosocial treatment intervention uses a combination of interoceptive exposure therapy and elements of acceptance and commitment therapy (ACT) and psychoeducation about benzodiazepine use in OAT. Of note, this is a pilot trial for feasibility and acceptability. There is no randomization and we are not comparing arms.

Behavioral: Distress Tolerance - Benzodiazepine Discontinuation (DT-BD); Distress Tolerance - Benzodiazepine Discontinuation (DT-BD) is a psychosocial intervention. It is paired with a benzodiazepine taper. The aim of the psychosocial intervention is to improve individuals' ability to tolerate distress in order to assist benzodiazepine discontinuation in patients treated with OAT. There will be 5 sessions between therapist and participant prior to the start of the benzodiazepine taper. The taper for both the intervention and control conditions occurs over 9 weeks and involves weekly meetings with a benzodiazepine prescriber during which a gradual benzodiazepine dose reduction will take place. The DT-BD intervention combines elements of existing psychosocial interventions. Specifically, interoceptive exposure techniques will be paired with elements of acceptance and commitment therapy (ACT) and relapse prevention (RP).; Drug: BZD discontinuation protocol; All participants will undergo BZD discontinuation. Once the starting BZD dose is determined by prescription monitoring and/or self-report, we will maintain participants on this dose until the start of the BZD taper. Participants will see a study physician weekly to receive their BZD medication for the week until the taper is completed. BZD discontinuation in this study will consist of a gradual BZD taper in dose over 9 weeks. The taper will be flexible in that the study physician will utilize clinical judgement to lengthen the taper if necessary, depending on the severity of the participant's withdrawal symptoms. Anchor points will be set (33% reduction in dose after 2 weeks, 50% mid-treatment, 100% by week 8) to emphasize the time-limited nature of the taper.; Other Names: Benzodiazepine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Participant Acceptability of the Interventions	Number of participants who rated the intervention as acceptable, this was assessed by conducting an in-depth exit interview with the participant once they complete the entire 13-week study.	13 weeks
Number of Participants Who Rates the Intervention as Feasible	Feasibility of intervention will be measured through the number of participants recruited and enrolled in the study, number of participants who started the BZD taper, and completed assessment tools.	13 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Completion of Intervention	Completion of intervention will be measured through participant attendance of weekly sessions. Participants must attend all 13 sessions (Baseline, 3 weekly therapy sessions prior to taper, and 8 week BZD taper urine/drug screens). Participants, who miss a study visit, will be considered discontinued from the study if study staff are unable to get in contact with them 7 days after their missed study visit.	13 weeks
BZD Use Based on Self-report	Timeline follow-back will be measured using the 30-day Timeline Followback (TLFB), adapted for BZD use. The Timeline Followback (TLFB) is a clinical and research method to obtain quantitative estimates of drug or alcohol use, and change over time. Participants will be asked to retrospectively estimate their BZD use 7 days prior to study visit. We will also monitor BZD use on a daily basis with a mobile phone application.	13 weeks
Illicit Drug Use Based on Urine Drug Tests	Illicit drug use urine tests will screen for amphetamines, benzodiazepines, opiates, oxycodone, fentanyl, cocaine, barbiturates, and methadone. Plus: liquid chromatography-mass spectrometry for clonazepam and lorazepam, and fentanyl if fentanyl test (immunoassay) is positive.	13 weeks
Alcohol Use Based on Urine Drug Tests	Urine drug tests will include a ethyl glucuronide (EtG) test to detect the presence in the urine of ethyl glucuronide.	13 weeks
Alcohol Use Based on Self-report	Timeline follow-back will be measured using the 30-day Timeline Followback (TLFB). The Timeline Followback (TLFB) is a clinical and research method to obtain quantitative estimates of drug or alcohol use, and change over time. Participants will be asked to retrospectively estimate their alcohol use 7 days prior to study visit. The alcohol adaption includes estimates of 1 standard drink in terms of beer, wine, and hard liquor. We will also monitor alcohol use on a daily basis with a mobile phone application.	13 weeks
BZD Withdrawal Symptoms	BZD withdrawal symptoms will be measured using the Clinical Institute Withdrawal Assessment-Benzodiazepines (CIWA-B). The CIWA-B is a 20 item instrument, to assess severity of benzodiazepine withdrawal, including nausea and vomiting, anxiety, tremor, sweating, auditory disturbances, visual disturbances, tactile disturbances, headache, agitation, and clouding of sensorium. Scores range from 0 to 80, with 1-20 mild withdrawal, 21-40 moderate withdrawal, 41-60 severe withdrawal, and 61-80 very severe withdrawal.	13 weeks
Anxiety Symptoms	The Overall Anxiety Severity and Impairment Scale (OASIS) is a 5-item self-report measure that can be used to assess severity and impairment associated with any anxiety disorder or multiple anxiety disorders.	13 weeks
Depressive Symptoms	The Patient Health Questionnaire (PHQ)-9 is the major depressive disorder (MDD) module of the full PHQ. It is used to diagnose depression and grade severity of symptoms in general medical and mental health settings. Scores each of the 9 DSM criteria of MDD as "0" (not at all) to "3" (nearly every day), providing a 0-27 severity score.	13 weeks
Sleep Quality	Sleep quality will be measured using the Pittsburgh Sleep Quality Index (PSQI), a 9 item self report instrument, designed to measure quality and patterns of sleep from very good to very bad. Sleep quality will also be measured on a daily basis with a mobile phone application. A global score of 5 or more indicates poor sleep quality; the higher the score, the worse the quality.	13 weeks
Inability to Tolerate Negative States	The Distress Intolerance (DI) Index will be used to assess Inability to tolerate negative states.The index is a 10 item self-report measure designed to assess the inability to tolerate negative states. Items are rated from 0 (very little) to 4 (very much) and are summed for a total score, with higher scores indicating greater DI.	13 weeks
Inflexibility or Experiential Avoidance	The Acceptance and Action Questionnaire-II will be used to measure inflexibility or experiential avoidance. It is a 7 item self-report measure of psychological inflexibility or experiential avoidance. Each of the 7 items can be rated on a scale of 1 (never true) to 7 (always true) so scores can range from 7 to 49. Higher scores equal greater levels of psychological inflexibility.	13 weeks
Fear of Anxiety Symptoms	Fear of anxiety symptoms will be assessed by the Anxiety Sensitivity Index. It is a 16 item scale with each item rated on a five-point Likert scale ranging from 0 (very little) to 4 (very much). Scores can range from 0 to 64. Higher scores reflect greater fear of anxiety symptoms.	13 weeks
Number of Participants Assessed for Distress Tolerance	Distress tolerance will be assessed with the computerized Mirror Tracing Persistence Task (MTPT-C). It is a computerized version of the original Mirror Tracing Persistence Task in which trace multiple progressively difficult polygons, with participants free to terminate at any point. Distress tolerance is measured by the latency in seconds to task termination.	13 weeks
Number of Participants Assessed for Motivations to Use BZD	BZD motivations will be measured using the 12 item BZD Motivation Scale, a self report questionnaire. The questionnaire uses a 4 point Likert scale to assess participant motivations for using BZD, such as managing pain, insomnia, anxiety, and increase high of other illicit drugs.	13 weeks

Collaborators and Investigators

• Sponsor: Boston Medical Center
• Collaborators: National Institute on Drug Abuse (NIDA)
• Investigators: Principal Investigator: Tae Woo Park, MD, Boston Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2021
• Primary Completion (Actual): July 8, 2021
• Study Completion (Actual): July 8, 2021

Study Registration Dates

• First Submitted: September 25, 2019
• First Submitted That Met QC Criteria: September 27, 2019
• First Posted (Actual): September 30, 2019

Study Record Updates

• Last Update Posted (Actual): February 11, 2022
• Last Update Submitted That Met QC Criteria: January 20, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Benzodiazepine; Opioid agonist therapy; Distress tolerance; Distress Tolerance - Benzodiazepine Discontinuation (DT-BD); Relaxation Therapy (RT)
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders
• Other Study ID Numbers: H-38981; 1K23DA044321-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes