Back to resultsTranscutaneous Auricular Neurostimulation (tAN) for Symptoms of Opioid Withdrawal
Primary Purpose
Opioid-use Disorder, Opioid Withdrawal
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
transcutaneous auricular neurostimulation (tAN)
Sponsored by
About this trial
This is an interventional treatment trial for Opioid-use Disorder focused on measuring auricular neurostimulation, vagus nerve stimulation, transcutaneous, withdrawal symptoms
Eligibility Criteria
Inclusion Criteria:
- Current opioid dependence; prescriptive or non-prescriptive
- COWS score is ≥ 13 or in the opinion of the investigator the subject is in moderate to severe withdrawal
- 18-65 years of age
- English Proficiency
- Participants must be able to provide informed con-sent and function at an intellectual level sufficient for study requirements
Exclusion Criteria:
- Current evidence of an uncontrolled and/or clinically significant medical condition
- History of seizures or epilepsy
- 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
- Recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation
- Presence of devices, e.g. pace-makers, cochlear prosthesis, neuro-stimulators
- Abnormal ear anatomy or ear infection present
- 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
- 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
- Recovery Unplugged
Arms of the Study
Arm 1
Arm 2
Arm Type
Sham Comparator
Experimental
Arm Label
delayed-active tAN
active tAN
Arm Description
Outcomes
Primary Outcome Measures
Clinical opiate withdrawal scale (COWS) score
Mean percent change in clinical opiate withdrawal scale (COWS) score from baseline to 60 minutes after start of active tAN therapy. The COWS is an 11-item scale with a score range between 0 and 48. Total score is the sum of all the items and 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.
Secondary Outcome Measures
Clinical opiate withdrawal scale (COWS) score
Comparison of mean percent change in COWS score in delayed active tAN versus active tAN groups at 30 minutes
Clinical opiate withdrawal scale (COWS) responder rate
Comparison of the proportion of participants with a clinically significant reduction in COWS score (defined as a 15% or greater reduction) in delayed-active tAN versus active tAN groups at 30 minutes
Clinical opiate withdrawal scale (COWS) score
Mean percent change in COWS score from baseline to 30 minutes after start of active tAN therapy
Clinical opiate withdrawal scale (COWS) score
Mean percent change in COWS score from baseline to 120 minutes after start of active tAN therapy
Clinical opiate withdrawal scale (COWS) score
Mean percent change in COWS score from baseline to Days 2 through 5 after start of active tAN therapy
Full Information
NCT ID
NCT04075214
First Posted
August 28, 2019
Last Updated
August 17, 2021
Sponsor
Spark Biomedical, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04075214
Brief Title
Transcutaneous Auricular Neurostimulation (tAN) for Symptoms of Opioid Withdrawal
Official Title
Delivering Transcutaneous Auricular Neurostimulation (tAN) to Improve Symptoms Associated With Opioid Withdrawal
Study Type
Interventional
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
November 19, 2019 (Actual)
Primary Completion Date
December 14, 2020 (Actual)
Study Completion Date
December 14, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Spark Biomedical, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
Clinical performance data for transcutaneous auricular neurostimulation (tAN) as a method to aid in the reduction of symptoms associated with opioid withdrawal in order to support clinical substantial equivalence to a predicate device.
Detailed Description
Prior evidence has demonstrated that non-invasive neurostimulation can modulate specific brains regions associated with opioid use disorder and reduce opioid withdrawal symptoms. This is a double blind, randomized, controlled, multi-center study in which subjects will be randomized in a 1:1 ratio to one of two groups: 1) active transcutaneous auricular neurostimulation (tAN) or 2) delayed-active tAN to determine reduction of symptoms related to opioid withdrawal. Subjects in the active tAN group will receive tAN immediately whereas those in the delayed-active tAN will have their therapy turned on after a 30 minute delay (inactive period). All subjects will be informed of their group assignment at the conclusion of the randomized, double blind period (following initial 30 minutes of active or inactive therapy) and all will continue to receive active tAN throughout the five-day study. Each clinical site will have pre-determined and qualified clinical opiate withdrawal scale (COWS) accessor(s) that will be blind to the subjects group designation during the randomized, double blind period and will not be informed that all subjects receive active therapy throughout the remainder of the study. This will ensure a non-biased assessment of the COWS score and maintain single blinding throughout the duration of the study.
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
35 (Actual)
8. Arms, Groups, and Interventions
Arm Title
delayed-active tAN
Arm Type
Sham Comparator
Arm Title
active tAN
Arm Type
Experimental
Intervention Type
Device
Intervention Name(s)
transcutaneous auricular neurostimulation (tAN)
Intervention Description
Phoenix tAN system
Primary Outcome Measure Information:
Title
Clinical opiate withdrawal scale (COWS) score
Description
Mean percent change in clinical opiate withdrawal scale (COWS) score from baseline to 60 minutes after start of active tAN therapy. The COWS is an 11-item scale with a score range between 0 and 48. Total score is the sum of all the items and 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
Secondary Outcome Measure Information:
Title
Clinical opiate withdrawal scale (COWS) score
Description
Comparison of mean percent change in COWS score in delayed active tAN versus active tAN groups at 30 minutes
Time Frame
30 minutes
Title
Clinical opiate withdrawal scale (COWS) responder rate
Description
Comparison of the proportion of participants with a clinically significant reduction in COWS score (defined as a 15% or greater reduction) in delayed-active tAN versus active tAN groups at 30 minutes
Time Frame
30 minutes
Title
Clinical opiate withdrawal scale (COWS) score
Description
Mean percent change in COWS score from baseline to 30 minutes after start of active tAN therapy
Time Frame
30 minutes
Title
Clinical opiate withdrawal scale (COWS) score
Description
Mean percent change in COWS score from baseline to 120 minutes after start of active tAN therapy
Time Frame
120 minutes
Title
Clinical opiate withdrawal scale (COWS) score
Description
Mean percent change in COWS score from baseline to Days 2 through 5 after start of active tAN therapy
Time Frame
Days 2-5
Other Pre-specified Outcome Measures:
Title
Heart rate variability measured by R to R interval
Description
Mean change from baseline to Days 2-5 in heart rate variability measured by R to R interval
Time Frame
Days 2-5
Title
C-reactive protein (CRP) levels
Description
Mean change in C-reactive protein (CRP) levels from baseline to Day 5
Time Frame
Day 5
Title
Cortisol levels
Description
Mean change in cortisol levels from baseline to Day 5
Time Frame
Day 5
Title
Cytokine levels
Description
Mean change in cytokine levels from baseline to Day 5
Time Frame
Day 5
Title
Patient Health Questionnaire (PHQ-9)
Description
Mean change in depression symptoms measured by Patient Health Questionnaire (PHQ-9) total score from baseline to Day 5. The PHQ-9 is a nine-item depression scale 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
Day 5
Title
Post-Traumatic Stress Disorder (PTSD) Checklist for DSM-5 (PCL-5)
Description
Mean change in PTSD symptoms measured by the PTSD Checklist for DSM-5 (PCL-5) total symptom severity score from baseline to Day 5. The PCL-5 is a 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. 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 a10-20 point reduction in score represents a clinically significant change in PTSD symptoms.
Time Frame
Day 5
Title
World Health Organization Quality of Life - BREF (WHOQOL-BREF)
Description
Mean change in WHOQOL-BREF domain scores (physical health, psychological health, social relationships, environment, and overall QoL/general health) from baseline to Day 5. The World Health Organization Quality of Life - BREF (WHOQOL-BREF) is a 26-item, self-report questionnaire which assesses 4 quality of life domains: physical health, psychological health, social relationships, and environment. In addition, there are 2 items that measure overall quality of life and general health. Subjects 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. Raw domain scores will be converted to a 0 to 100 scale.
Time Frame
Day 5
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:
Current opioid dependence; prescriptive or non-prescriptive
COWS score is ≥ 13 or in the opinion of the investigator the subject is in moderate to severe withdrawal
18-65 years of age
English Proficiency
Participants must be able to provide informed con-sent and function at an intellectual level sufficient for study requirements
Exclusion Criteria:
Current evidence of an uncontrolled and/or clinically significant medical condition
History of seizures or epilepsy
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
Recent suicide attempt leading to current hospital admission or continued expressed suicidal ideation
Presence of devices, e.g. pace-makers, cochlear prosthesis, neuro-stimulators
Abnormal ear anatomy or ear infection present
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
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Navid Khodaparast, PhD
Organizational Affiliation
Spark Biomedical, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Recovery Unplugged
City
Austin
State/Province
Texas
ZIP/Postal Code
78745
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
35978394
Citation
Tirado CF, Washburn SN, Covalin A, Hedenberg C, Vanderpool H, Benner C, Powell DP, McWade MA, Khodaparast N. Delivering transcutaneous auricular neurostimulation (tAN) to improve symptoms associated with opioid withdrawal: results from a prospective clinical trial. Bioelectron Med. 2022 Aug 18;8(1):12. doi: 10.1186/s42234-022-00095-x.
Results Reference
derived
Learn more about this trial
Transcutaneous Auricular Neurostimulation (tAN) for Symptoms of Opioid Withdrawal
We'll reach out to this number within 24 hrs