Bridge: An Innovative Intervention for OUD Treatment

Sponsor
Johns Hopkins University (Other)
Overall Status
Recruiting
CT.gov ID
NCT04325659
Collaborator
National Institute on Drug Abuse (NIDA) (NIH)
75
1
3
35.4
2.1

Study Details

Study Description

Brief Summary

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.

Condition or Disease Intervention/Treatment Phase
  • Device: Bridge Device
  • Drug: Lofexidine
  • Drug: Placebo
  • Device: Sham Bridge Device
Phase 2/Phase 3

Study Design

Study Type:
Interventional
Anticipated Enrollment :
75 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Evaluating a Neuromodulator Medical Device (Bridge Device) for Opioid Use Disorder Treatment
Actual Study Start Date :
Nov 15, 2020
Anticipated Primary Completion Date :
Oct 30, 2023
Anticipated Study Completion Date :
Oct 30, 2023

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Lofexidine/Sham Bridge Device

Lofexidine (Lucemyra) encapsulated

Drug: Lofexidine
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.
Other Names:
  • Lucemyra
  • Device: Sham Bridge Device
    Inactive Bridge Device which is applied and looks identical to the active Bridge Device
    Other Names:
  • Sham NSS-2 Bridge Device
  • Placebo Comparator: Sham Bridge Device /Placebo Study Drug

    Inactive Bridge Device and placebo study drug

    Drug: Placebo
    Inactive study drug, encapsulated to look like the active study drug. Participants will receive capsules 4 times daily for 7 days.

    Device: Sham Bridge Device
    Inactive Bridge Device which is applied and looks identical to the active Bridge Device
    Other Names:
  • Sham NSS-2 Bridge Device
  • Experimental: Active Bridge Device/ Placebo Study Drug

    Active Bridge Device and placebo study drug

    Device: Bridge Device
    An FDA-cleared neuromodulator medical device, marketed for the treatment of opioid withdrawal
    Other Names:
  • NSS-2 Bridge Device
  • Drug: Placebo
    Inactive study drug, encapsulated to look like the active study drug. Participants will receive capsules 4 times daily for 7 days.

    Outcome Measures

    Primary Outcome Measures

    1. Proportion of participants retained [Up to 5 days]

      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.

    2. Withdrawal Severity as measured by Clinical Opiate Withdrawal Scale (COWS) peak score [At the end of day 5]

      Peak COWS Score (range: 0-48). Lower peak COWS scores are indicative of better withdrawal suppression.

    3. Withdrawal Severity as measured by area under the curve COWS score [At the end of day 5]

      Area under the curve COWS scores (range: 0-240). Smaller area under the curve COWS scores are indicative of better withdrawal suppression.

    4. Withdrawal Severity as measured by COWS peak daily score [Up to 5 days]

      Peak daily COWS score (range: 0-48). Lower peak daily COWS scores are indicative of better withdrawal suppression.

    Secondary Outcome Measures

    1. Proportion of participants retained [At the end of day 9]

      The proportion of participants who are retained (dichotomous: retained, not retained) during the 9 day intervention. Greater retention is indicative of better intervention outcome.

    2. Withdrawal severity as measured by the Subjective Opiate Withdrawal Scale (SOWS) peak score [At the end of day 5]

      Peak SOWS Score (range: 0-64). Lower peak SOWS scores are indicative of better withdrawal suppression.

    3. Withdrawal severity as measured by area under the curve SOWS score [At the end of day 5]

      Area under the curve SOWS scores (range: 0-320). Smaller area under the curve SOWS scores are indicative of better withdrawal suppression.

    4. Withdrawal severity as measured by the SOWS peak daily score [Up to 5 days]

      Peak daily SOWS score (range: 0-64). Lower peak daily SOWS scores are indicative of better withdrawal suppression.

    5. Proportion of Participants who initiate naltrexone at the end of the study [At the end of day 9]

      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.

    6. Number of concomitant medications used [Up to 5 days]

      Number of concomitant medications used per day. A smaller number of concomitant medications used per day is indicative of better treatment efficacy.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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)

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Behavioral Pharmacology Research Unit Baltimore Maryland United States 21224

    Sponsors and Collaborators

    • Johns Hopkins University
    • National Institute on Drug Abuse (NIDA)

    Investigators

    • Principal Investigator: Eric Strain, Johns Hopkins University

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Johns Hopkins University
    ClinicalTrials.gov Identifier:
    NCT04325659
    Other Study ID Numbers:
    • IRB00241133
    • R01DA048761
    First Posted:
    Mar 27, 2020
    Last Update Posted:
    Dec 14, 2021
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    Yes
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Dec 14, 2021