An Innovative Intervention for OUD Treatment

NCT04325659 | Completed Phase 2 FDA Drug FDA Device

• 2 other identifiers: IRB00241133R01DA048761
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Opioid-Related Disorders; Opioid Dependence; Opioid Addiction; Opioid Withdrawal

Outcome Measures

Primary Outcomes (4)

• 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 Outcomes (6)

• Proportion of participants retained

  At the end of day 9

• Withdrawal severity as measured by the Subjective Opiate Withdrawal Scale (SOWS) peak score

  At the end of day 5

• Withdrawal severity as measured by area under the curve SOWS score

  At the end of day 5

• Withdrawal severity as measured by the SOWS peak daily score

  Up to 5 days

• Proportion of Participants who initiate naltrexone at the end of the study

  At the end of day 9

Study Arms (3)

Lofexidine/Sham Bridge Device

ACTIVE COMPARATOR

Lofexidine (Lucemyra) encapsulated

Drug: Lofexidine; Device: Sham Bridge Device

Sham Bridge Device /Placebo Study Drug

PLACEBO COMPARATOR

Inactive Bridge Device and placebo study drug

Drug: Placebo; Device: Sham Bridge Device

Active Bridge Device/ Placebo Study Drug

EXPERIMENTAL

Active Bridge Device and placebo study drug

Device: Bridge Device; Drug: Placebo

Interventions

Bridge Device DEVICE

An FDA-cleared neuromodulator medical device, marketed for the treatment of opioid withdrawal

Also known as: NSS-2 Bridge Device

Active Bridge Device/ Placebo Study Drug

Lofexidine DRUG

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.

Also known as: Lucemyra

Lofexidine/Sham Bridge Device

Placebo DRUG

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

Active Bridge Device/ Placebo Study Drug; Sham Bridge Device /Placebo Study Drug

Sham Bridge Device DEVICE

Inactive Bridge Device which is applied and looks identical to the active Bridge Device

Also known as: Sham NSS-2 Bridge Device

Lofexidine/Sham Bridge Device; Sham Bridge Device /Placebo Study Drug

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Behavioral Pharmacology Research Unit

Baltimore, Maryland, 21224, United States

Location

MeSH Terms

Conditions

Opioid-Related Disorders

Interventions

lofexidine

Condition Hierarchy (Ancestors)

Narcotic-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Study Officials

• Eric Strain

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is of a device (the Bridge Device), not of a drug.

Study Record Dates

• First Submitted: March 25, 2020
• First Posted: March 27, 2020
• Study Start: November 15, 2020
• Primary Completion: April 20, 2025
• Study Completion: January 1, 2026
• Last Updated: February 11, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)