tAN for PTSD and OUD in Buprenorphine Therapy

Study Overview
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Brief Summary
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The goal of this research study is to investigate the effects transcutaneous auricular neurostimulation (tAN), as delivered through the Sparrow Ascent device, on helping people with co-occurring posttraumatic stress disorder (PTSD) and opioid use disorder (OUD) start and continue buprenorphine treatment. The main questions it aims to answer are: Does the tAN help participants with OUD and PTSD remain in buprenorphine therapy for three months after starting use of the device (i.e., randomization to treatment condition)? Do participants find the Sparrow Ascent device to be acceptable and use it? Do participants find the Sparrow Ascent device to be tolerable and comfortable to use? Do participants find the Sparrow Ascent device to be easy to use with their buprenorphine therapy? Do participants follow the minimum recommended dose schedule for the Sparrow Ascent device most of the time? Participants will complete a baseline assessment to make sure that they are eligible to participate in the study. The assessment captures information about demographics, substance use and treatment history, opioid withdrawal symptoms and craving, difficult life experiences and PTSD symptoms, mental health and treatment history, quality of life, and recovery resources. After the assessment is complete and the participant has been inducted on buprenorphine as part of standard care in the clinic, they are randomized to one of two treatment conditions: active tAN and placebo. Participants are trained on how to use the device and return for 12 weekly research visits to check on recent substance use and craving, PTSD symptoms, and their experience using the device. After 12 weeks of using the device, participants will complete a post-active treatment assessment that is nearly identical to the baseline assessment to see if there have been changes in these areas. Researchers will access the medical record to determine whether there is a current prescription for buprenorphine at three months and six months after randomization.

Official Title
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IMBUE RETAIN: Transcutaneous Auricular Neurostimulation (tAN) for Patients With Co-occurring Posttraumatic Stress Disorder (PTSD) and Opioid Use Disorder Starting Buprenorphine Therapy

Conditions
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Posttraumatic Stress Disorder, Opioid Use Disorder

Intervention / Treatment
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* Device: Sparrow Ascent tAN
* Device: Sparrow Ascent Active Sham


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65. Admitted as a patient seeking buprenorphine therapy for opioid use disorder and able to be randomized within 7 days of induction on buprenorphine. Meets Diagnostic and Statistical Manual - 5 (DSM-5) diagnostic criteria for moderate to severe opioid use disorder with induction on buprenorphine. This includes volunteers who have taken buprenorphine in the past and are re-starting, are currently receiving non-buprenorphine medication for opioid use disorder, or have taken non-buprenorphine medication for opioid use disorder in the past and are transitioning to buprenorphine therapy for the first time. Meets DSM-5 diagnostic criteria for posttraumatic stress disorder (PTSD). Able to understand the study, and having understood, provide written informed consent in English. Provides permission to extract data from the participant's electronic medical record. Exclusion Criteria: Unable to provide sufficient contact information (must provide at least two reliable indicators). Volunteers currently receiving buprenorphine therapy with another agency and transitioning their buprenorphine care to the study site without an induction on buprenorphine. Volunteers who intend to, or will receive, inpatient substance use disorder (SUD) care at the time of buprenorphine (BUP) induction. Volunteers receiving inpatient detoxification care at the time of screening or baseline assessment are eligible if they will no longer be receiving inpatient care when they are inducted on buprenorphine. Volunteers actively participating in evidence-based psychotherapy for PTSD (e.g., Prolonged Exposure, Cognitive Processing Therapy, etc.). Volunteers who will not have been stable on medications that affect PTSD (i.e., sertraline, paroxetine, venlafaxine, prazosin, or trazodone) for at least four weeks before they could be randomized. Volunteer presents current evidence of an uncontrolled and/or clinically significant medical or psychiatric condition that will impact their ability to comply with the study requirements or would make their study participation unsafe. This includes unmedicated bipolar disorder with a manic episode in the past month or unmedicated psychotic disorder. Volunteer has a history of epileptic seizure. Volunteer has a history of neurological disorder or traumatic brain injury with significant lasting effects (e.g., memory problems, emotional changes, behavioral changes). Volunteer had a suicide attempt leading to hospital admission in the past month or suicidal ideation with a plan and intent to act upon it in the past month. Volunteer has the presence of devices (e.g., pacemakers, cochlear prosthesis, neurostimulators). Volunteer has abnormal ear anatomy or an ear infection is present. Volunteer is pregnant or lactating. Volunteers of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study's active participation period (i.e., 12 weeks following randomization). Volunteer has any other significant medical or psychosocial problems that, in the opinion of the investigator, would potentially cause harm to the participant, impact their ability to participate, or influence the results of the project's trial. These include circumstances such as impending incarceration, moving out of the area, or a general history of noncompliance.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 1:1 randomization
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active tAN<br>Participants receive active tAN with the Sparrow Ascent device from Spark Biomedical (Dallas, TX). | Device: Sparrow Ascent tAN<br>* The Sparrow Ascent device from Spark Biomedical (Dallas, TX), applies stimulation frequencies of 15 Hz at the cymba concha (vagal innervation) and 100 Hz anterior to the tragus (trigeminal innervation). Both tAN and active sham conditions have square biphasic waveforms with identical pulse widths of 250 µs separated by a 125 µs interval between pulses. Stimulation is applied using a duty cycle of 5-minutes ON and 10 seconds OFF. The stimulation intensities (mA) will be programmed for each individual based on the highest amplitude for each channel that is both comfortable and perceptible. Patients using the device may alter the intensity of stimulation at these sites using the Patient Controller to achieve the desired effect.<br>* Other names: Sparrow Ascent tAN System;|
| Sham Comparator: Active Sham<br>Participants receive the active sham version of the Sparrow Ascent device that limits stimulation to trigeminal innervation only and at a charge that is approximately 1000x lower than the active tAN condition. | Device: Sparrow Ascent Active Sham<br>* The Sparrow Ascent Active Sham is a modified version of the Sparrow Ascent tAN System that has been designed to provide sub-therapeutic stimulation to the trigeminal nerve only and no stimulation to the vagus nerve. The trigeminal nerve will receive 1 Hz stimulation at the temporomandibular region at an amplitude that is comfortable and perceptual. The pulse duration will be set to a value that does not exceed 250 μs in a square biphasic waveform. The patient controller device for the active sham will give the appearance that stimulation is being applied at both vagal and trigeminal electrode sites.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 3-month Buprenorphine (BUP) Retention | 3-month BUP retention, operationalized as a current BUP prescription at the time of data extraction (retained/not retained), will be examined by observing the proportion of participants who are retained in BUP therapy at 3 months post-randomization. | 3 months post-randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Device Acceptability | The proportion of participants registering use of the device. | 3 months post-randomization | 
| Device Tolerability | The proportions of participants endorsing that the device caused pain or discomfort to the ear, discontinue the study due to a device-related Adverse Event (AE), and any device-related Serious Adverse Events (SAEs). | 3 months post-randomization | 
| Device Feasibility - Patient Ease of Use | The proportion of participants who endorse that the device was easy to use as measured by the Device Usability Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Patient Helpfulness | The proportion of participants who endorse that the device helped them take their buprenorphine as prescribed as measured by the Device Usability Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Patient Value | The proportion of participants who endorse that the device is valuable for people with PTSD and OUD taking buprenorphine as measured by the Device Usability Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Provider Helpfulness | The proportion of provider reports of patient device usage endorsing that the device helped their participants take their buprenorphine as prescribed as measured by the Provider Feedback Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Provider Utility | The proportion of provider reports of patient device usage endorsing that the device has utility as an adjunct to buprenorphine therapy as measured by the Provider Feedback Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Provider Value | The proportion of provider reports of patient device usage endorsing that the device has value as a treatment option for patients with PTSD and OUD taking buprenorphine as measured by the Provider Feedback Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Feasibility - Provider Barrier | The proportion of provider reports of patient device usage endorsing that the device does not make it harder for their participant to take their medication as measured by the Provider Feedback Questionnaire using a five-item ordinal scale ranging from Strongly disagree to Strongly agree. | 3 months post-randomization | 
| Device Adherence | The proportion of participants who meet or exceed the minimum dosing schedule for at least 75% (9 of 12) weekly research visits. | 3 months post-randomization | 
| Buprenorphine Medication Compliance | The proportions of weekly research visits with a positive result for buprenorphine in the urine drug test and self-reported buprenorphine administration as prescribed. | 3 months post-randomization | 
| Substance Use | The proportions of weekly research visits with self-reported non-prescribed substance use (e.g., opioid use, stimulant use) as measured by the Timeline Follow-back Method and positive urine drug test results. | 3 months post-randomization | 
| PTSD Symptom Severity - Self Rated | Mean change in PTSD Checklist for DSM-5 (PCL-5) symptom severity scores from baseline to post-treatment assessment. PCL-5 scores range from 0 - 80 with a higher score indicating more severe trauma-related distress due to PTSD symptoms. | 3 months post-randomization | 
| PTSD Symptom Severity - Clinician Rated | Mean change in Clinician-administered PTSD Scale for DSM-5 (CAPS-5) symptom severity scores from baseline to post-treatment assessment. CAPS-5 scores range from 0 - 80 with a higher score indicating more severe trauma-related distress due to PTSD symptoms. | 3 months post-randomization | 
| PTSD Remission Status | Change in PTSD diagnostic status according to the Clinician-administered PTSD Scale for DSM-5 (CAPS-5). | 3 months post-randomization | 
| Opioid Withdrawal Symptom Severity - Self Rated | Mean change in self-reported opioid withdrawal symptom severity on the 10-item Short Opiate Withdrawal Scale - Gossop (SOWS-Gossop). Participants rate each item on a scale ranging from 0 (None) to 3 (Severe). The total scale score ranges between 0 - 30, with higher scores indicating more severe withdrawal symptoms. | 3 months post-randomization | 
| Opioid Withdrawal Symptom Severity - Observer Rated | Mean change in observer-rated severity on the 11-item Clinical Opiate Withdrawal Scale (COWS). The total score on the measure ranges from 0-48, with higher scores indicating greater severity of opioid withdrawal signs and symptoms. | 3 months post-randomization | 
| Opioid-related Craving | Mean change in self-reported opioid craving scores on the five-item Penn Craving Scale (PCS). Total scores on this measure range from 0 - 30, with higher scores indicating more severe craving for opioids. | 3 months post-randomization | 
| Overall Quality of Life and General Health | Mean change in self-reported Overall Quality of Life and General Health domain scores using the United States version of the World Health Organization (WHO) Quality of Life Scale - Brief. Participants rate items using a five-point Likert scale ranging from Not at all (1) to Completely (5). Raw scores within this domain range from 2-10. Higher scores indicate a higher overall quality of life and general health. | 3 months post-randomization | 
| Physical Health | Mean change in self-reported Physical Health domain scores using the United States version of the WHO Quality of Life Scale - Brief. Participants rate items using a five-point Likert scale ranging from Not at all (1) to Completely (5). Raw scores within this domain range from 7-35. Higher scores indicate a higher quality of physical health. | 3 months post-randomization | 
| Psychological Health | Mean change in self-reported Psychological domain scores using the United States version of the WHO Quality of Life Scale - Brief. Participants rate items using a five-point Likert scale ranging from Not at all (1) to Completely (5). Raw scores within this domain range from 6-30. Higher scores indicate a higher quality of psychological health. | 3 months post-randomization | 
| Quality of Social Relationships | Mean change in self-reported Social Relationships domain scores using the United States version of the WHO Quality of Life Scale - Brief. Participants rate items using a five-point Likert scale ranging from Not at all (1) to Completely (5). Raw scores within this domain range from 3-15. Higher scores indicate a higher quality of social relationships. | 3 months post-randomization | 
| Quality of Environment | Mean change in self-reported Environment domain scores using the United States version of the WHO Quality of Life Scale - Brief. Participants rate items using a five-point Likert scale ranging from Not at all (1) to Completely (5). Raw scores within this domain range from 8-40. Higher scores indicate a higher quality of environment. | 3 months post-randomization | 
| Recovery Capital | Mean change in self-reported recovery capital scores on the Brief Assessment of Recovery Capital - 10 (BARC-10). Scores on this measure range from 6-60, with higher scores indicating greater recovery capital and a higher likelihood of sustaining recovery from substance use disorder. | 3 months post-randomization | 
| Depression Symptom Severity | Mean change in self-reported depression symptom severity as measured by the Patient Health Questionnaire - 9 (PHQ-9). Scores on this measure range from 0-27, with higher scores indicating more severe depression-related distress. | 3 months post-randomization | 
| Anxiety Symptom Severity | Mean change in self-reported depression symptom severity as measured by General Anxiety Disorder - 7 (GAD-7). Scores on this measure range from 0-21, with higher scores indicating more severe anxiety-related distress. | 3 months post-randomization | 
| Blinding to Condition | The proportion of participants randomized to the comparison group who believe that they were in the active tAN condition. | 3 months post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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feasibility, medication for opioid use disorder (buprenorphine), treatment retention, transcutaneous auricular neurostimulation