tAN for PTSD and OUD in Buprenorphine Therapy

Posttraumatic Stress Disorder Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06130501
• Other study ID #: 1UG3DA059409-01
• Status: Recruiting
• Phase: N/A
• Start date: June 14, 2024
• Est. completion date: June 2025

Study information

• Verified date: June 2024
• Source: University of Cincinnati
• Contact: Ashley Naeger, MSW
• Phone: 573-803-4158
• Email: naegera[@]gibsonrecovery.org
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

The overall UG3/UH3 phased project will test transcutaneous auricular neurostimulation (tAN) to the trigeminal and vagus nerves via the Sparrow Ascent device as an adjunct intervention to improve retention in buprenorphine treatment (BUP) for patients with co-occurring opioid use disorder and posttraumatic stress disorder. The specific objectives of the UG3 project are to:

1. conduct a pilot randomized, active sham-controlled test of transcutaneous auricular neurostimulation (tAN) with the Sparrow Ascent device to determine its acceptability, tolerability, feasibility, and adherence in patients with OUD and PTSD starting buprenorphine (BUP) therapy;

2. submit progress for review regarding study milestones and go/no-go criteria for approval of the UH3 phase; and

3. complete FDA pre-submission for FDA input on proposed UH3 protocols to expand Sparrow Ascent's indication for PTSD symptoms.

Approximately twenty adults diagnosed with opioid use disorder and posttraumatic stress disorder initiating buprenorphine treatment at Gibson Center for Behavioral Change will complete a baseline assessment of substance use and mental health diagnostic measures before being randomized into the study. Participants randomized to the active tAN condition will receive therapeutic stimulation to the trigeminal and vagus nerves through the Sparrow Ascent earpiece when they activate their Patient Controller. Participants randomized to the active sham condition will receive only stimulation on the trigeminal nerve at a level that can be felt but is well below any therapeutic effect. All participants will receive identical training for the Sparrow Ascent device and the only difference will be the condition-dependent programming of their Patient Controllers. Participants begin using the Sparrow Ascent device within one week of buprenorphine induction at Gibson. For the next 12 weeks, as they continue through standard buprenorphine treatment with Gibson providers, participants will independently administer stimulation at or above a recommended dosage schedule that decreases in frequency every four weeks during the active participation period (i.e., Weeks 1-4, 5-8, 9-12). Device usage logs will be downloaded and assessed at weekly research visits throughout the active participation period to determine device adherence and provide feedback and assistance, if needed. After 12 weeks of device usage, participants return their device and complete a post-assessment that repeats many of the baseline assessments to determine changes from baseline. Buprenorphine treatment retention (primary outcome) at three months and six months (secondary outcome) post-randomization will be extracted from the electronic medical record.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 20
• Est. completion date: June 2025
• Est. primary completion date: March 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Opioid Use Disorder
• Opioid-Related Disorders
• Posttraumatic Stress Disorder
• Stress Disorders, Post-Traumatic
• Stress Disorders, Traumatic
• Substance-Related Disorders

Intervention

Device:
• Sparrow Ascent tAN
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.
• Sparrow Ascent Active Sham
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.

Locations

Country	Name	City	State
United States	Gibson Center for Behavioral Change	Cape Girardeau	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	Spark Biomedical, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Weekly PTSD Symptom Severity	Weekly ratings of self-reported PTSD symptom severity on the PTSD Checklist for DSM-5 (PCL-5). PCL-5 scores range from 0 - 80 with a higher score indicating more severe trauma-related distress due to PTSD symptoms.	Weekly for 3 months post-randomization
Other	Weekly Opioid Withdrawal Symptom Severity Self Rated	Weekly ratings of opioid withdrawal symptom severity on the 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.	Weekly for 3 months post-randomization
Other	Weekly Opioid Withdrawal Symptom Severity Observer Rated	Weekly ratings of opioid withdrawal symptom severity on the 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.	Weekly for 3 months post-randomization
Other	Weekly Opioid-related Craving	Weekly ratings of self-reported opioid-related craving on the PCS. Total scores on this measure range from 0 - 30, with higher scores indicating more severe craving for opioids.	Weekly for 3 months post-randomization
Other	Weekly Substance Use	Weekly non-prescribed substance use as indicated by Timeline Follow-back and urine drug test.	Weekly for 3 months post-randomization
Other	Bi-weekly Depression Symptom Severity	Bi-weekly scores on the Patient Health Questionnaire - 9 (PHQ-9). Scores on this measure range from 0-27, with higher scores indicating more severe depression-related distress.	Bi-weekly for 3 months post-randomization
Other	Bi-weekly Anxiety Symptom Severity	Bi-weekly scores on the General Anxiety Disorder - 7 (GAD-7). Scores on this measure range from 0-21, with higher scores indicating more severe anxiety-related distress.	Bi-weekly for 3 months post-randomization
Primary	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	Device Acceptability	The proportion of participants registering use of the device.	3 months post-randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	PTSD Remission Status	Change in PTSD diagnostic status according to the Clinician-administered PTSD Scale for DSM-5 (CAPS-5).	3 months post-randomization
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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