Benzodiazepine Discontinuation in Opioid Agonist Therapy

Substance Use Disorders Clinical Trial

— BZD-OAT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04109118
• Other study ID #: H-38981
• Secondary ID: 1K23DA044321-01
• Status: Completed
• Phase: Phase 2
• Start date: March 18, 2021
• Est. completion date: July 8, 2021

Study information

• Verified date: January 2022
• Source: Boston Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4
• Est. completion date: July 8, 2021
• Est. primary completion date: July 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Substance Use Disorders
• Substance-Related Disorders

Intervention

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.

Locations

Country	Name	City	State
United States	Boston Medical Center	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Boston Medical Center	National Institute on Drug Abuse (NIDA)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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