Bridge Device + Lofexidine for Opioid Use Disorder

(Bridge Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Eric Strain, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Johns Hopkins University

Must not be taking: Opioid agonists, Medical cannabis, 2D6 inhibitors

Disqualifiers: Pregnancy, Diabetes, Schizophrenia, Alcohol dependence, others

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

This trial is testing a device called the Bridge Device, which uses electrical signals to help people with opioid addiction. The study focuses on individuals who are not currently on any medication for their addiction. The device aims to ease withdrawal symptoms by sending signals to the brain. Participants will be monitored to see if the device effectively reduces withdrawal symptoms.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you are receiving opioid agonist treatment or using medical cannabis. Also, you cannot be on certain medications like strong 2D6 inhibitors.

What data supports the effectiveness of the Bridge Device and Lofexidine treatment for opioid use disorder?

Research shows that the Bridge Device, which stimulates nerves behind the ear, can help reduce symptoms of opioid withdrawal and pain, making it easier for people to stop using opioids. Additionally, Lofexidine is known to help manage withdrawal symptoms, suggesting that combining these treatments could be effective. ^{1 2 3 4 5}

Is the combination of Bridge Device and Lofexidine safe for humans?

Lofexidine has been studied for its safety in treating opioid withdrawal, and research indicates it is generally safe with no serious adverse events reported in studies. However, specific safety data for the combination of the Bridge Device and Lofexidine is not available in the provided research. ^{6 7 8 9 10}

How is the Bridge Device + Lofexidine treatment different from other treatments for opioid use disorder?

The Bridge Device is unique because it is a non-invasive treatment that uses electrical nerve stimulation to help reduce opioid withdrawal symptoms, unlike traditional medication-based therapies. It targets specific nerves in the ear to modulate pain and withdrawal symptoms, offering an alternative to pharmacological approaches. ^{1 2 3 4 8}

Research Team

Eric Strain, MD

Principal Investigator

Johns Hopkins University

Eligibility Criteria

This trial is for adults aged 18-65 with Opioid Use Disorder seeking treatment, who are in good health and not using opioid agonist treatments or have significant medical conditions like heart issues, liver or kidney impairment. Participants must test positive for opioids or show withdrawal symptoms but can't be pregnant, breastfeeding, or have certain psychiatric illnesses.

Inclusion Criteria

No significant psychiatric illnesses besides OUD

Meets Diagnostic and Statistical Manual-5 criteria for Opioid Use Disorder (OUD) (moderate or severe) based upon Mini-International Neuropsychiatric Interview (MINI)

Willing to comply with the study protocol

Exclusion Criteria

My liver or kidney function tests are higher than normal.

Have a known allergy to any of the study medications

Significant medical illness (e.g., insulin dependent diabetes)

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

Stabilization

Participants are stabilized on morphine for 7-11 days and undergo a precipitated withdrawal challenge using naloxone

7-11 days

Treatment

Participants use the Bridge Device for 5 days and receive study drug for 7 days

7 days

Monitoring

Participants are monitored for 4 days after device removal to determine whether withdrawal resumes

4 days

Follow-up

Participants are encouraged to begin treatment with oral naltrexone followed by extended release naltrexone and are assisted with engaging in outpatient treatment

4 days

Treatment Details

Interventions

• Bridge Device (Neuromodulator Medical Device)
• Lofexidine (Drug)
• Placebo (Drug)
• Sham Bridge Device (Device)

Trial Overview The study tests the Bridge Device (BD), a neuromodulator cleared by the FDA for OUD treatment. It compares three groups: one with active BD and placebo pills, another with a sham BD and lofexidine (a non-opioid medication to ease withdrawal), and a third group with both sham BD and placebo. The efficacy of these interventions during opioid withdrawal will be evaluated over several weeks.

Participant Groups

Group I: Active Bridge Device/ Placebo Study Drug Experimental Treatment 2 Interventions

Active Bridge Device and placebo study drug

Group II: Lofexidine/Sham Bridge Device Active Control 2 Interventions

Lofexidine (Lucemyra) encapsulated

Group III: Sham Bridge Device /Placebo Study Drug Placebo Group 2 Interventions

Inactive Bridge Device and placebo study drug

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Theodore DeWeese

Johns Hopkins University

Chief Executive Officer since 2023

MD from an unspecified institution

Allen Kachalia

Johns Hopkins University

Chief Medical Officer since 2023

MD from an unspecified institution

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Dr. Jeanne Marrazzo

National Institutes of Health (NIH)

Chief Medical Officer

MD from University of California, Los Angeles

Dr. Jay Bhattacharya

National Institutes of Health (NIH)

Chief Executive Officer

MD, PhD from Stanford University

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Executive Officer since 2003

MD from National Autonomous University of Mexico

Dr. Nora Volkow

National Institute on Drug Abuse (NIDA)

Chief Medical Officer since 2003

MD from National Autonomous University of Mexico

Findings from Research

The BRIDGE® device significantly reduced opioid withdrawal scores in patients, with a 62.7% reduction at 20 minutes and a remarkable 97.1% reduction by day 5, indicating its efficacy as a non-pharmacological treatment.

In this pilot study of 73 adult patients, 88.8% successfully transitioned to medication-assisted therapy (MAT) after using the BRIDGE, suggesting it may facilitate smoother transitions during opioid withdrawal.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. Miranda, A., Taca, A.[2018]

The NET Device is a non-invasive treatment designed to help people with opioid use disorder (OUD) quit opioids without medication, and it is currently being tested in a clinical trial with 100 participants (50 receiving active treatment and 50 receiving sham treatment).

The trial aims to determine the safety and effectiveness of the NET Device by measuring the percentage of weeks participants remain abstinent from illicit opioids over a 12-week period, providing a potential new approach to treating OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized, sham-controlled, quintuple-blinded trial to evaluate the NET device as an alternative to medication for promoting opioid abstinence. Greenwald, MK., Ghosh, S., Winston, JR.[2022]

The NSS-2 BRIDGE device significantly reduced opioid consumption by 60.2% and pain levels by 28% in patients after gastric bypass surgery, indicating its potential effectiveness in pain management.

The device was well-tolerated by patients, with tolerability ratings considered excellent, suggesting it could be a viable alternative to traditional pain relief methods post-surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass. Ahmed, BH., Courcoulas, AP., Monroe, AL., et al.[2022]

The auricular neuromodulation device (NSS-2 Bridge) was used off-label in 5 patients after knee and hip surgeries, showing promising results in reducing pain and opioid use during recovery.

Patients reported low pain levels (median 0 to 2 on a 0-10 scale) and minimal oxycodone consumption (median 0 to 2.5 mg) post-surgery, with one patient completely avoiding opioids, suggesting the device may effectively provide analgesia and reduce reliance on opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Percutaneous Auricular Nerve Stimulation (Neuromodulation) for Analgesia and Opioid-Sparing Following Knee and Hip Arthroplasty: A Proof-of-Concept Case Series. Finneran, JJ., Said, ET., Ball, ST., et al.[2023]

The FDA has approved two non-invasive electrical nerve stimulators that can help alleviate acute opioid withdrawal symptoms by stimulating cranial nerves behind the ear, showing promise as an adjunct treatment.

This method of auricular electrical neural stimulation has the potential to enhance medication-assisted treatment for opioid detoxification, offering lower side effects and potentially improving patient adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Auricular neural stimulation as a new non-invasive treatment for opioid detoxification. Qureshi, IS., Datta-Chaudhuri, T., Tracey, KJ., et al.[2021]

Lofexidine has been recently FDA approved for treating opioid withdrawal symptoms in adults and has shown effectiveness in randomized controlled trials compared to placebo.

The safety profile of lofexidine is favorable, and its efficacy is comparable to other first- and second-line treatments for opioid withdrawal, although its higher cost may limit its accessibility in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. Doughty, B., Morgenson, D., Brooks, T.[2020]

Lofexidine, at doses of 2.16 mg and 2.88 mg per day, significantly reduced opioid withdrawal symptoms compared to placebo in a study involving 603 participants over 7 days, demonstrating its efficacy as a nonopioid treatment for opioid withdrawal syndrome.

The study also found that lofexidine improved completion rates of the withdrawal program by 14% and 12% compared to placebo, indicating it not only helps manage symptoms but also encourages patients to complete the treatment process.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. Fishman, M., Tirado, C., Alam, D., et al.[2020]

In a preliminary study involving 18 opioid-dependent patients, those treated with lofexidine alongside naltrexone showed higher rates of opioid abstinence and better relapse outcomes compared to those receiving a placebo.

Lofexidine treatment also resulted in lower heart rates and reduced cravings triggered by stress and drug cues, suggesting it may effectively help manage stress-related cravings in opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. Sinha, R., Kimmerling, A., Doebrick, C., et al.[2022]

Lofexidine, an alpha(2)-agonist, has been shown to effectively reduce opioid withdrawal symptoms in a review of nine clinical studies involving 354 patients, demonstrating efficacy comparable to opioid receptor agonists used for detoxification.

While lofexidine can alleviate many withdrawal symptoms, it may not address all issues, such as insomnia and aches, and it has a lower incidence of adverse effects compared to clonidine, making it a promising non-opioid option for opioid detoxification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. Gish, EC., Miller, JL., Honey, BL., et al.[2013]

In a 10-week outpatient trial with 20 adults, lofexidine was found to be a feasible option for managing opioid withdrawal, allowing 50% of participants to successfully receive their first injection of extended-release naltrexone (ER-NTX).

The study reported no serious adverse events related to the treatment, indicating that lofexidine is a safe option for facilitating the induction of ER-NTX in individuals with opioid use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder. Mariani, JJ., Basaraba, C., Pavlicova, M., et al.[2023]

References

1. England pubmed.ncbi.nlm.nih.gov

Neuromodulation with percutaneous electrical nerve field stimulation is associated with reduction in signs and symptoms of opioid withdrawal: a multisite, retrospective assessment. [2018]

2. Netherlands pubmed.ncbi.nlm.nih.gov

A randomized, sham-controlled, quintuple-blinded trial to evaluate the NET device as an alternative to medication for promoting opioid abstinence. [2022]

3. United States pubmed.ncbi.nlm.nih.gov

Auricular nerve stimulation using the NSS-2 BRIDGE device to reduce opioid requirement following laparoscopic Roux-en-Y gastric bypass. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Percutaneous Auricular Nerve Stimulation (Neuromodulation) for Analgesia and Opioid-Sparing Following Knee and Hip Arthroplasty: A Proof-of-Concept Case Series. [2023]

5. England pubmed.ncbi.nlm.nih.gov

Auricular neural stimulation as a new non-invasive treatment for opioid detoxification. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Lofexidine: A Newly FDA-Approved, Nonopioid Treatment for Opioid Withdrawal. [2020]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Lofexidine for Medically Managed Opioid Withdrawal: A Randomized Controlled Clinical Trial. [2020]

8. Germany pubmed.ncbi.nlm.nih.gov

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. [2022]

9. United States pubmed.ncbi.nlm.nih.gov

Lofexidine, an {alpha}2-receptor agonist for opioid detoxification. [2013]

10. England pubmed.ncbi.nlm.nih.gov

Open label trial of lofexidine-assisted non-opioid induction onto naltrexone extended-release injection for opioid use disorder. [2023]