Back to resultsDelivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder (RESTORE)
Primary Purpose
Opioid-use Disorder, Opioid Withdrawal
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Sparrow Ascent Therapy System
Lofexidine
Extended-release injectable naltrexone
Sponsored by
About this trial
This is an interventional prevention trial for Opioid-use Disorder focused on measuring auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms, relapse prevention
Eligibility Criteria
Inclusion Criteria
- Participant shows signs of current opioid dependence; prescription or non-prescription
- Participant COWS score is ≥ 8 or in the opinion of the investigator the participant is in mild to moderate withdrawal at the baseline assessment
- Participant is between 18 and 65 years of age
- Participant is English proficient
- Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements
Exclusion Criteria
- Participant presents current evidence of an uncontrolled and/or clinically significant medical condition or psychiatric condition
- Participant has a history of epileptic seizures
- Participant has a history of neurological diseases or traumatic brain injury
- Participants using long-acting opioids such as methadone or buprenorphine for a period of five or more consecutive days prior to enrollment
- Participant has recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation
- Participant has presence of devices, e.g., pacemakers, cochlear prosthesis, neurostimulators
- Participant has abnormal ear anatomy or ear infection present
- Participant is unwilling to transition to opioid antagonist medication following acute detox treatment
- Subject has significant current suicidal ideation within 30 days prior to Screening as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening, that, in the opinion of the investigator, warrants exclusion from the trial
- Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study
- Females who are pregnant or lactating
- Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
Sites / Locations
- Hazelden Betty Ford FoundationRecruiting
- Gaudenzia, Inc.Recruiting
- Hazelden Betty Ford FoundationRecruiting
- Hazelden Betty Ford Foundation
- Hazelden Betty Ford Foundation
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Placebo Comparator
Active Comparator
No Intervention
Sham Comparator
Active Comparator
Experimental
Arm Label
Active tAN + placebo
Active tAN + lofexidine
Sham tAN + placebo
Sham tAN + lofexidine
extended-release injectable naltrexone
Active tAN + extended-release injectable naltrexone
Arm Description
tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.
tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.
Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.
Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.
Extended-release injectable naltrexone will be administered according to the clinical site's standard of care.
Extended-release injectable naltrexone will be administered according to the clinical site's standard of care. Participants will be provided with a Spark Sparrow Ascent Therapy System and instructed to administer therapy according to the specified frequencies: Month 1 (Days 1 - 28): a minimum of 2 hours per day at least 5 days a week Month 2 (Days 29 - 56): a minimum of 2 hours per day at least 3 days a week Month 3 (Days 57 - 90: a minimum of 2 hours per day at least 1 day per week
Outcomes
Primary Outcome Measures
14-Panel Urine Drug Screen
In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.
Self-Report of Drug Use
In Phase II, participants will be asked weekly to self-report any use of opioids to determine if opioids have been used in the past week (in conjunction with a UDS sample).
Secondary Outcome Measures
Clinical Opiate Withdrawal Scale (COWS)
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Clinical Opiate Withdrawal Scale (COWS)
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Clinical Opiate Withdrawal Scale (COWS)
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Opioid Craving Scale (OCS)
The 3-item Opioid Craving Scale was adapted from the 3-item Cocaine Craving Scale for use with opioids. The original 5-item version was found to be valid and unidimensional among cocaine-dependent individuals. Participants are asked to answer the following three questions with responses ranging from 0-10, where 0 = Not at all and 10 = Extremely. Total possible score ranges from 0 to 30 with greater scores indicating higher opioid craving.
How much do you currently crave opiates?
In the past week, please rate how strong your desire to use opiates has been when something in the environment has reminded you of opiates?
Please imagine yourself in the environment in which you previously used opiates. If you were in this environment today and if it were the time of day that you typically used opiates, what is the likelihood that you would use opiates today?
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Proportion of patients who receive and tolerate an XR-NTX injection after acute detox treatment (Phase I)
Full Information
NCT ID
NCT05053503
First Posted
August 16, 2021
Last Updated
August 2, 2023
Sponsor
Spark Biomedical, Inc.
Collaborators
Hazelden Betty Ford Foundation, Gaudenzia, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT05053503
Brief Title
Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder
Acronym
RESTORE
Official Title
Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 25, 2022 (Actual)
Primary Completion Date
August 2024 (Anticipated)
Study Completion Date
August 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spark Biomedical, Inc.
Collaborators
Hazelden Betty Ford Foundation, Gaudenzia, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The primary objective of this trial is to determine whether tAN can improve relapse prevention beyond that seen with extended-release injectable naltrexone during Phase II.
Detailed Description
This is a prospective, randomized, controlled, multi-center, clinical trial in which participants with a history of dependence on prescriptive or non-prescriptive opioids will be randomized 2:1 into one of four treatment groups during Phase I (acute detoxification, 7 days):
Group 1: Active tAN + placebo
Group 2: Active tAN + lofexidine
Group 3: Sham tAN + placebo
Group 4: Sham tAN + lofexidine
Phase I will occur during the participant's treatment in a residential detox center. Participants will have the option to continue into Phase II of the trial at the conclusion of their stay in the residential detox treatment program. In Phase II, participants will be re-randomized 1:1 into one of two treatment groups and will return weekly for 90 days:
Group 1: Extended-release injectable naltrexone
Group 2: Active tAN + extended-release injectable naltrexone
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Opioid-use Disorder, Opioid Withdrawal
Keywords
auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms, relapse prevention
7. Study Design
Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Model Description
This is a prospective, randomized, controlled, multi-center, clinical trial in which participants with a history of dependence on prescriptive or non-prescriptive opioids will be randomized 2:1 into one of four treatment groups during Phase I (acute detoxification). Phase I will occur during the participant's treatment in a residential detox center. Participants will have the option to continue into Phase II of the trial at the conclusion of their stay in the residential detox treatment program. In Phase II, participants will be re-randomized 1:1 into one of two treatment groups.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
All study investigators will be blind to patient treatment group assignment. Furthermore, each clinical site will have pre-determined and qualified COWS assessors that will be blind to randomization group assignment. This will ensure a non-biased assessment of opioid withdrawal symptoms. Information regarding study intervention will be withheld from the blinded COWS assessors. All participants will be blinded to their group assignment during acute detox treatment (Phase I). Participants will not be unblinded to their Phase I treatment until study exit, which may occur at the end of Phase II for participants who continue in the study. Participants will not be blinded to their treatment group during Phase II.
Allocation
Randomized
Enrollment
168 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active tAN + placebo
Arm Type
Placebo Comparator
Arm Description
tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.
Arm Title
Active tAN + lofexidine
Arm Type
Active Comparator
Arm Description
tAN will be delivered at a duty cycle of for 5 minutes ON and 10 seconds OFF for up to 168 hours (7 days) therapy duration. Stimulation intensity will be customized to the participants comfort level and within range of therapeutic effectiveness. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.
Arm Title
Sham tAN + placebo
Arm Type
No Intervention
Arm Description
Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 placebo pills four times per day for 7 days. The placebo will appear similar to lofexidine in size, shape, color, and smell to lofexidine.
Arm Title
Sham tAN + lofexidine
Arm Type
Sham Comparator
Arm Description
Participants will have the earpiece applied and the cable connected to the Patient Controller, but tAN stimulation will not be turned on. Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.
Arm Title
extended-release injectable naltrexone
Arm Type
Active Comparator
Arm Description
Extended-release injectable naltrexone will be administered according to the clinical site's standard of care.
Arm Title
Active tAN + extended-release injectable naltrexone
Arm Type
Experimental
Arm Description
Extended-release injectable naltrexone will be administered according to the clinical site's standard of care. Participants will be provided with a Spark Sparrow Ascent Therapy System and instructed to administer therapy according to the specified frequencies:
Month 1 (Days 1 - 28): a minimum of 2 hours per day at least 5 days a week
Month 2 (Days 29 - 56): a minimum of 2 hours per day at least 3 days a week
Month 3 (Days 57 - 90: a minimum of 2 hours per day at least 1 day per week
Intervention Type
Device
Intervention Name(s)
Sparrow Ascent Therapy System
Intervention Description
Transcutaneous auricular neurostimulation (tAN)
Intervention Type
Drug
Intervention Name(s)
Lofexidine
Intervention Description
Participants will receive 3 lofexidine 0.18 mg/tablets four times per day (daily dose of 2.16 mg) for 7 days.
Intervention Type
Drug
Intervention Name(s)
Extended-release injectable naltrexone
Intervention Description
Participants will receive extended-release injectable naltrexone based on the clinical site's standard of care.
Primary Outcome Measure Information:
Title
14-Panel Urine Drug Screen
Description
In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.
Time Frame
Weekly throughout Phase II (13 weeks)
Title
Self-Report of Drug Use
Description
In Phase II, participants will be asked weekly to self-report any use of opioids to determine if opioids have been used in the past week (in conjunction with a UDS sample).
Time Frame
Weekly throughout Phase II (13 weeks)
Secondary Outcome Measure Information:
Title
Clinical Opiate Withdrawal Scale (COWS)
Description
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Time Frame
60 minutes after treatment initiation (Day 1, Phase I)
Title
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
Description
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Time Frame
60 minutes after treatment initiation (Day 1, Phase I)
Title
Clinical Opiate Withdrawal Scale (COWS)
Description
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Time Frame
6 hours after treatment initiation (Day 1, Phase I)
Title
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
Description
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Time Frame
6 hours after treatment initiation (Day 1, Phase I)
Title
Clinical Opiate Withdrawal Scale (COWS)
Description
The Clinical Opiate Withdrawal Scale (COWS) is an 11-item scale designed to be administered by a clinician. This tool can be used in both inpatient and outpatient settings to reproducibly rate common signs and symptoms of opiate withdrawal and monitor these symptoms over time. The summed score for the complete scale can be used to help clinicians determine the stage or severity of opiate withdrawal and assess the level of physical dependence on opioids. Scores range between 0 and 48 where total score is the sum of all the items. A higher score indicates more severe withdrawal symptoms. Scores between 5 and 12 indicate mild withdrawal, scores between 13 and 24 indicate moderate withdrawal, scores between 25 and 36 indicate moderately severe withdrawal and scores greater than 36 indicate severe withdrawal. A COWS score reduction of 15% or greater for a given individual is considered clinically significant.
Time Frame
Daily on Days 2-7 of Phase I
Title
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
Description
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Time Frame
Daily on Days 2-7 of Phase I
Title
Opioid Craving Scale (OCS)
Description
The 3-item Opioid Craving Scale was adapted from the 3-item Cocaine Craving Scale for use with opioids. The original 5-item version was found to be valid and unidimensional among cocaine-dependent individuals. Participants are asked to answer the following three questions with responses ranging from 0-10, where 0 = Not at all and 10 = Extremely. Total possible score ranges from 0 to 30 with greater scores indicating higher opioid craving.
How much do you currently crave opiates?
In the past week, please rate how strong your desire to use opiates has been when something in the environment has reminded you of opiates?
Please imagine yourself in the environment in which you previously used opiates. If you were in this environment today and if it were the time of day that you typically used opiates, what is the likelihood that you would use opiates today?
Time Frame
Weekly throughout Phase II (13 weeks)
Title
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop)
Description
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Time Frame
Weekly throughout Phase II (13 weeks)
Title
Proportion of patients who receive and tolerate an XR-NTX injection after acute detox treatment (Phase I)
Time Frame
One hour after receiving first XR-NTX injection (Phase II Day 1)
Other Pre-specified Outcome Measures:
Title
Patient Health Questionnaire (PHQ-9) in Phase I
Description
The PHQ-9 is a validated tool in mental health and considered a powerful tool to assist clinicians with diagnosing depression and monitoring treatment response. The relationship between opioid use and depression is bidirectional. The PHQ-9 is a nine-item depression scale and is based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each of the nine items is rated on a 0 (not at all) to 3 (nearly every day) scale. A total score is calculated by summing the nine items. Scores range from 0 to 27 and higher scores indicate a higher degree of depression.
Time Frame
Baseline and Day 7
Title
Patient Health Questionnaire (PHQ-9) in Phase II
Description
The PHQ-9 is a validated tool in mental health and considered a powerful tool to assist clinicians with diagnosing depression and monitoring treatment response. The relationship between opioid use and depression is bidirectional. The PHQ-9 is a nine-item depression scale and is based directly on the nine diagnostic criteria for major depressive disorder in the DSM-IV. Each of the nine items is rated on a 0 (not at all) to 3 (nearly every day) scale. A total score is calculated by summing the nine items. Scores range from 0 to 27 and higher scores indicate a higher degree of depression.
Time Frame
Monthly throughout Phase II (Day 28, 56, and 90)
Title
PTSD Checklist for DSM-5 (PCL-5) in Phase I
Description
Symptoms of post-traumatic stress disorder (PTSD) and opiate dependency may overlap, to which, opioid withdrawal symptoms may emulate PTSD hyperactive startle response. This is indicative a common physiological mechanism. The PCL-5 scale is the gold standard in PTSD assessment. It consisted of a 20-item self-report measurement that is capable of measuring symptom change during and after treatment. Additionally, the scale can provide a provisional PTSD diagnosis. Each of the 20 items is rated on a 0 (not at all) to 4 (extremely) scale. A total symptom severity score is calculated by summing the 20 items. Scores range from 0 and 80 and higher scores indicating a higher degree of PTSD symptomology. Evidence suggests that a10 to 20-point reduction in score represents a clinically significant change in PTSD symptoms.
Time Frame
Baseline and Day 7
Title
PTSD Checklist for DSM-5 (PCL-5) in Phase II
Description
Symptoms of post-traumatic stress disorder (PTSD) and opiate dependency may overlap, to which, opioid withdrawal symptoms may emulate PTSD hyperactive startle response. This is indicative a common physiological mechanism. The PCL-5 scale is the gold standard in PTSD assessment. It consisted of a 20-item self-report measurement that is capable of measuring symptom change during and after treatment. Additionally, the scale can provide a provisional PTSD diagnosis. Each of the 20 items is rated on a 0 (not at all) to 4 (extremely) scale. A total symptom severity score is calculated by summing the 20 items. Scores range from 0 and 80 and higher scores indicating a higher degree of PTSD symptomology. Evidence suggests that a10 to 20-point reduction in score represents a clinically significant change in PTSD symptoms.
Time Frame
Monthly throughout Phase II (Day 28, 56, and 90)
Title
Generalized Anxiety Disorder (GAD-7) in Phase I
Description
The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research. The questionnaire consists of 7 questions in which participants are asked to rate each item on a 0 (not at all) to 3 (nearly every day). GAD-7 total score for the seven items ranges from 0 to 21 where 0-4 represents minimal anxiety, 5-9 represents mild anxiety, 10-14 represents moderate anxiety and 15-21 represent severe anxiety.
Time Frame
Baseline and Day 7
Title
Generalized Anxiety Disorder (GAD-7) in Phase II
Description
The GAD-7 is a valid and efficient tool for screening for GAD and assessing its severity in clinical practice and research. The questionnaire consists of 7 questions in which participants are asked to rate each item on a 0 (not at all) to 3 (nearly every day). GAD-7 total score for the seven items ranges from 0 to 21 where 0-4 represents minimal anxiety, 5-9 represents mild anxiety, 10-14 represents moderate anxiety and 15-21 represent severe anxiety.
Time Frame
Monthly throughout Phase II (Day 28, 56, and 90)
Title
World Health Organization Quality of Life (WHOQOL-BREF) in Phase I
Description
The WHOQOL-BREF is a shorter version of the original assessment tool and is commonly used in clinical trials with participants undergoing substance use disorder intervention. The WHOQOL-BREF is comprised of 26-items and assesses the participant's quality of life across specific domains: physical health, psychological health, social relationships, and environment. In addition, there are 2 items that measure overall quality of life and general health. Participants rate how much they have experienced each item in the preceding 2 weeks on a 5-point Likert scale ranging from 1 (not at all) to 5 (completely). Domain scores are scaled in a positive direction with higher scores denoting higher quality of life. The mean score of items within each domain is used to calculate the domain score. Raw domain scores will be converted to a 0 to 100 scale.
Time Frame
Baseline and Day 7
Title
World Health Organization Quality of Life (WHOQOL-BREF) in Phase II
Description
The WHOQOL-BREF is a shorter version of the original assessment tool and is commonly used in clinical trials with participants undergoing substance use disorder intervention. The WHOQOL-BREF is comprised of 26-items and assesses the participant's quality of life across specific domains: physical health, psychological health, social relationships, and environment. In addition, there are 2 items that measure overall quality of life and general health. Participants rate how much they have experienced each item in the preceding 2 weeks on a 5-point Likert scale ranging from 1 (not at all) to 5 (completely). Domain scores are scaled in a positive direction with higher scores denoting higher quality of life. The mean score of items within each domain is used to calculate the domain score. Raw domain scores will be converted to a 0 to 100 scale.
Time Frame
Monthly throughout Phase II (Day 28, 56, and 90)
Title
Brief Assessment of Recovery Capital (BARC-10) from Phase I to Phase II
Description
The BARC-10 is a short,10-item measure that examines recovery capital globally. Items were selected from the ARC for the BARC-10 using item response theory. The BARC-10 measures a unidimensional (i.e., global) construct of recovery capital across all the original 10 domains of the ARC. On average, it takes 2-5 minutes to complete. Scores range from 6-60. Individuals who have a recovery capital score of 47 or higher are likely to reach or sustain a year or longer of recovery from substance use disorder.
Time Frame
Baseline, Day 7, and monthly throughout Phase II (Day 28, 56, and 90)
Title
Short Opiate Withdrawal Scale-Gossop (SOWS-Gossop) in Phase II
Description
The SOWS-Gossop is an appropriate, precise, and sensitive measure to evaluate the symptoms of acute opioid withdrawal in research or clinical settings. The scale was derived from the original 32-item Opiate Withdrawal Scale to reduce redundancy while providing an equally sensitive measure of opioid withdrawal symptom severity appropriate for research and clinical practice. The assessment is a self-administered test used for the assessment of opiate withdrawal symptoms. The scale contains ten items: yawning, muscular tension, runny eyes, muscle twitching, pains, and aches, feeling of coldness, stomach cramps, insomnia, heart pounding, and feeling sick, making it easy and rapid to administer. The tool has a 4-point rating scale: 0 for 'none,' 1 for 'mild,' 2 for 'moderate,' and 3 for 'severe', with scores ranging from 0 to 30.
Time Frame
Weekly throughout Phase II (13 weeks)
Title
14-Panel Urine Drug Screen in Phase I
Description
In Phase II, participants will provide a weekly urine sample to determine if opioids have been used in the past week (in conjunction with a self-report). A urine drug screen cup will be used to detect presence of: Amphetamines, Buprenorphine, Benzodiazepines, Cocaine, Ethyl Glucuronide, Fentanyl, Synthetic Marijuana, Ecstasy, Methamphetamines, Methadone, Opiates / Morphine, Oxycodone, Cannabinoid (Marijuana), and Tramadol. The urine drug screen cup also contains a temperature strip to confirm appropriate temperature of the sample and an adulteration panel for determination of sample tampering.
Time Frame
Baseline and Day 7
Title
Xylazine Test Strip Screen in Phase I and Phase II
Description
In addition to the 14-Panel Urine Drug Screen cup, a xylazine test strip will be used to detect the presence of xylazine in the urine.
Time Frame
Baseline, Phase I Day 7, and weekly throughout Phase II (13 weeks)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria
Participant shows signs of current opioid dependence; prescription or non-prescription
Participant COWS score is ≥ 8 or in the opinion of the investigator the participant is in mild to moderate withdrawal at the baseline assessment
Participant is between 18 and 65 years of age
Participant is English proficient
Participant is able to provide informed consent and function at an intellectual level sufficient for study requirements
Exclusion Criteria
Participant presents current evidence of an uncontrolled and/or clinically significant medical condition or psychiatric condition
Participant has a history of epileptic seizures
Participant has a history of neurological diseases or traumatic brain injury
Participants using long-acting opioids such as methadone or buprenorphine for a period of five or more consecutive days prior to enrollment
Participant has recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation
Participant has presence of devices, e.g., pacemakers, cochlear prosthesis, neurostimulators
Participant has abnormal ear anatomy or ear infection present
Participant is unwilling to transition to opioid antagonist medication following acute detox treatment
Subject has significant current suicidal ideation within 30 days prior to Screening as evidenced by answering "yes" to questions 4 or 5 on the suicidal ideation portion of the Columbia-Suicide Severity Rating Scale (C-SSRS) completed at Screening, that, in the opinion of the investigator, warrants exclusion from the trial
Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study
Females who are pregnant or lactating
Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants at risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Desirée Dorrough, CCRA
Phone
202-742-3875
Email
ddorrough@mcra.com
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Benner
Email
caroline.benner@sparkbiomedical.com
Facility Information:
Facility Name
Hazelden Betty Ford Foundation
City
Rancho Mirage
State/Province
California
ZIP/Postal Code
92270
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Susan Serice, MA
Email
sserice@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Alta DeRoo, MD
First Name & Middle Initial & Last Name & Degree
Quyen Ngo, PhD
First Name & Middle Initial & Last Name & Degree
Jacqueline Braughton, PhD
First Name & Middle Initial & Last Name & Degree
Olatunde Bosu, MD
Facility Name
Gaudenzia, Inc.
City
Crownsville
State/Province
Maryland
ZIP/Postal Code
21032
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eshawn Bell, LPN
Email
ebell@gaudenzia.org
First Name & Middle Initial & Last Name & Degree
Michelle Sobek, LPN
Email
msobek@gaudenzia.org
First Name & Middle Initial & Last Name & Degree
Philip Moore, DO
First Name & Middle Initial & Last Name & Degree
Mary Lilly, RN
Facility Name
Hazelden Betty Ford Foundation
City
Center City
State/Province
Minnesota
ZIP/Postal Code
55012
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara Cantwell, MPH
Email
tcantwell@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Mariam Lekuti
Email
mlekuti@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Alta DeRoo, MD
First Name & Middle Initial & Last Name & Degree
Quyen Ngo, PhD
First Name & Middle Initial & Last Name & Degree
Jacqueline Braughton, PhD
Facility Name
Hazelden Betty Ford Foundation
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55441
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara Cantwell, MPH
Email
tcantwell@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Mariam Lekuti
Email
mlekuti@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Alta DeRoo, MD
First Name & Middle Initial & Last Name & Degree
Quyen Ngo, PhD
First Name & Middle Initial & Last Name & Degree
Jacqueline Braughton, PhD
Facility Name
Hazelden Betty Ford Foundation
City
Plymouth
State/Province
Minnesota
ZIP/Postal Code
55441
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Tara Cantwell, MPH
Email
tcantwell@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Mariam Lekuti
Email
tcantwell@hazeldenbettyford.org
First Name & Middle Initial & Last Name & Degree
Alta DeRoo, MD
First Name & Middle Initial & Last Name & Degree
Quyen Ngo, PhD
First Name & Middle Initial & Last Name & Degree
Jacqueline Braughton, PhD
12. IPD Sharing Statement
Learn more about this trial
Delivering Transcutaneous Auricular Neurostimulation to Improve Relapse Prevention in Opioid Use Disorder
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