An Innovative Intervention for OUD Treatment

Study Overview
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Brief Summary
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The Bridge Device (BD) is a neuromodulator medical device that has been cleared by the FDA for Opioid Use Disorder (OUD) treatment. Importantly, medical devices reviewed by the FDA are cleared (based on safety) rather than approved (based on efficacy), which means the BD did not need to demonstrate efficacy before it became commercially available. As a result, the device was not required to have a sham-controlled trial for FDA clearance and there is no active research, to the investigators' knowledge, that specifically addresses the degree to which opioid withdrawal can be treated through neuromodulation. To rigorously evaluate the efficacy of the BD for treating OUD, the investigators will enroll persons with active OUD, not currently receiving medications for OUD. Participants will be recruited and admitted to the Clinical Research Unit (CRU) for a 2-3 week period. During participants' residential stay, participants will be stabilized for 7-11 days on four times daily morphine (30 mg, SC) and undergo a precipitated withdrawal challenge using the opioid antagonist naloxone, approximately >= 4 days of morphine maintenance. This is a standard practice for the investigators' study and allows the investigators to objectively assess dependence. The BD and study medication will begin following morphine stabilization. Participants will be randomly assigned to one of three conditions (1) active BD with placebo (BD/P), (2) sham BD with lofexidine (SBD/L), or (3) sham BD and placebo (SBD/P). Participants will use the BD for 5 days and will receive study drug for 7 days. Participants will be monitored for an additional 4 days after device removal to determine whether withdrawal resumes. Participants will undergo a second naloxone challenge after removal of the device/capsule completion to verify lack of opioid tolerance and will be encouraged to begin treatment with oral naltrexone followed by extended release naltrexone. Throughout the residential stay, all participants will be given referral to and assisted with engaging in outpatient treatment following study discharge.

Official Title
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Evaluating a Neuromodulator Medical Device (Bridge Device) for Opioid Use Disorder Treatment

Conditions
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Opioid-Related Disorders, Opioid Dependence, Opioid Addiction, Opioid Withdrawal

Intervention / Treatment
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* Device: Bridge Device
* Drug: Lofexidine
* Drug: Placebo
* Device: Sham Bridge Device


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age between 18 and 65 years old Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe) based upon Mini-International Neuropsychiatric Interview (MINI) Provides a urine sample that tests positive for opioids during screening or have evidence of opioid withdrawal Be in good general health based on a physical examination, medical history, vital signs, and screening urine and blood tests No significant psychiatric illnesses besides OUD Seeking treatment to stop using illicit opioids Willing to comply with the study protocol Have no clinically significant chronic medical or surgical disorders or conditions that are judged by the investigators to prevent participation Exclusion Criteria: Pregnant or breast feeding Receiving opioid agonist treatment Significant medical illness (e.g., insulin dependent diabetes) Significant psychiatric illness (e.g., schizophrenia) Use of medical cannabis Contraindications for use of the Bridge Device, morphine, lofexidine or naloxone (e.g., hemophilia, psoriasis and other skin conditions, a cardiac pacemaker) Have evidence of physical dependence on alcohol or benzodiazepines that requires medical detoxification Hypotension (diastolic blood pressure of less than 60 mm Hg or systolic blood pressure of less than 90 mm Hg on screening examination) Prolonged corrected QT interval interval on screening ECG (defined as >0.44 seconds for males and >0.46 seconds for females) Hepatic or renal impairment, as indicated by the following lab results at the screening session: Aspartate aminotransferase or alanine transaminase >3x upper limit of normal (ULN) Total Bilirubin >2x ULN. Creatinine >1.5x ULN. Treatment with a strong 2D6 inhibitor (e.g., paroxetine, thioridazine, cinacalcet, bupropion, methotrimeprazine, fluoxetine, midostaurin, propafenone, glycerol phenylbutyrate, halofantrine, cisapride, dacomitinib, orphenadrine, quinidine) Have a known allergy to any of the study medications Have circumstances that would interfere with study participation (e.g., impending jail)

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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Accepts Healthy Volunteers

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Lofexidine/Sham Bridge Device<br>Lofexidine (Lucemyra) encapsulated | Drug: Lofexidine<br>* FDA-approved medication for the treatment of opioid withdrawal. Participants will receive capsules 4 times daily for 7 days. The active dose is 0.72 mg four times daily for Days 1-5, for a total daily dose of 2.88 mg. Doses on Days 6 and 7 will be 1.44 (2 active, 2 placebo capsules) and 0.72 mg (1 active, 3 placebo capsules), respectively.<br>* Other names: Lucemyra;Device: Sham Bridge Device<br>* Inactive Bridge Device which is applied and looks identical to the active Bridge Device<br>* Other names: Sham NSS-2 Bridge Device;|
| Placebo Comparator: Sham Bridge Device /Placebo Study Drug<br>Inactive Bridge Device and placebo study drug | Drug: Placebo<br>* Inactive study drug, encapsulated to look like the active study drug. Participants will receive capsules 4 times daily for 7 days.<br>Device: Sham Bridge Device<br>* Inactive Bridge Device which is applied and looks identical to the active Bridge Device<br>* Other names: Sham NSS-2 Bridge Device;|
| Experimental: Active Bridge Device/ Placebo Study Drug<br>Active Bridge Device and placebo study drug | Device: Bridge Device<br>* An FDA-cleared neuromodulator medical device, marketed for the treatment of opioid withdrawal<br>* Other names: NSS-2 Bridge Device;Drug: Placebo<br>* Inactive study drug, encapsulated to look like the active study drug. Participants will receive capsules 4 times daily for 7 days.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants retained | The proportion of participants who are retained (dichotomous: retained, not retained) during the 5 day intervention. Greater retention is indicative of a better treatment outcome. | Up to 5 days | 
| Withdrawal Severity as measured by Clinical Opiate Withdrawal Scale (COWS) peak score | Peak COWS Score (range: 0-48). Lower peak COWS scores are indicative of better withdrawal suppression. | At the end of day 5 | 
| Withdrawal Severity as measured by area under the curve COWS score | Area under the curve COWS scores (range: 0-240). Smaller area under the curve COWS scores are indicative of better withdrawal suppression. | At the end of day 5 | 
| Withdrawal Severity as measured by COWS peak daily score | Peak daily COWS score (range: 0-48). Lower peak daily COWS scores are indicative of better withdrawal suppression. | Up to 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of participants retained | The proportion of participants who are retained (dichotomous: retained, not retained) during the 9 day intervention. Greater retention is indicative of better intervention outcome. | At the end of day 9 | 
| Withdrawal severity as measured by the Subjective Opiate Withdrawal Scale (SOWS) peak score | Peak SOWS Score (range: 0-64). Lower peak SOWS scores are indicative of better withdrawal suppression. | At the end of day 5 | 
| Withdrawal severity as measured by area under the curve SOWS score | Area under the curve SOWS scores (range: 0-320). Smaller area under the curve SOWS scores are indicative of better withdrawal suppression. | At the end of day 5 | 
| Withdrawal severity as measured by the SOWS peak daily score | Peak daily SOWS score (range: 0-64). Lower peak daily SOWS scores are indicative of better withdrawal suppression. | Up to 5 days | 
| Proportion of Participants who initiate naltrexone at the end of the study | The proportion of participants who initiate naltrexone (dichotomous: yes, no) at the end of day 9. A larger proportion of participants is indicative of better naltrexone initiation success. | At the end of day 9 | 
| Number of concomitant medications used | Number of concomitant medications used per day. A smaller number of concomitant medications used per day is indicative of better treatment efficacy. | Up to 5 days |