Bridge Device + Lofexidine for Opioid Use Disorder

(Bridge Trial)

Overseen By Cecilia L Bergeria, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Johns Hopkins University

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

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

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 7 days

75 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a device called the Bridge Device, designed to help treat opioid use disorder (OUD) by easing withdrawal symptoms through neuromodulation, which uses electrical signals to influence nerves. Participants will be divided into three groups: one with the active device and a placebo pill, another with a fake device and the medication lofexidine (used to manage withdrawal symptoms), and a final group with both a fake device and a placebo pill. The goal is to compare the device's effectiveness to the medication. Individuals with moderate to severe OUD who are not currently on other medications for OUD may be suitable for this study. As a Phase 2, Phase 3 trial, this study is crucial in assessing the treatment's effectiveness and is one step away from potential FDA approval, offering participants a chance to contribute to advancing OUD treatment.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

A previous study found that the Bridge Device, already approved by the FDA, helps reduce symptoms of opioid withdrawal. Most people use it without major problems, and while some side effects occur, they are usually mild.

Research has shown that lofexidine is also safe and effective for those experiencing opioid withdrawal. It is FDA approved, indicating it has undergone safety testing. Some individuals might experience side effects like low blood pressure or a slower heart rate, but these usually depend on the dose.

Both treatments have been used before and are considered safe for most participants. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Bridge Device and Lofexidine combination because of its unique approach to treating opioid use disorder. Unlike standard treatments like methadone or buprenorphine, which primarily target opioid receptors, the Bridge Device is a non-invasive neurostimulation device that aims to alleviate withdrawal symptoms by targeting nerve pathways in the ear. Lofexidine, on the other hand, is a non-opioid medication that helps reduce withdrawal symptoms without the risk of addiction. Together, this combination offers a promising alternative that could potentially ease withdrawal symptoms more effectively and safely than current options.

What evidence suggests that this trial's treatments could be effective for opioid use disorder?

Research has shown that the Bridge Device, a type of nerve stimulator, can help reduce opioid withdrawal symptoms. One study demonstrated that using this device led to at least a 30% decrease in these symptoms. Participants in this trial may receive the Active Bridge Device with a placebo study drug. Several studies have proven Lofexidine effective for easing opioid withdrawal. It works better than a placebo and helps people remain in treatment longer. In this trial, some participants will receive Lofexidine with a Sham Bridge Device. Both treatments aim to ease opioid withdrawal and keep patients committed to their recovery. ^{1 2 4 6 7}

Who Is on the Research Team?

Eric Strain, MD

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

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)

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Bridge Device
• Lofexidine
• Placebo
• Sham Bridge 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.

How Is the Trial Designed?

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

Bridge Device is already approved in United States for the following indications:

Approved in United States as NSS-2 Bridge for:

• Opioid Use Disorder (OUD) treatment
• Reduction of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

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]

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]

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]

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 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 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 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]

Citations

1. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/reviews/DEN170018.pdf

De Novo Summary (DEN170018) Page 1 of 1 NSS-2 BRIDGE ... The NSS-2 BRIDGE is a percutaneous nerve field stimulator (PNFS) system, that can be used as an aid to reduce the symptoms of opioid withdrawal, through ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04162145

BRIDGE Device for Treatment of Opioid Withdrawal The purpose of this study is to prospectively evaluate the effectiveness of the NSS-2 BRIDGE device in reducing the signs and symptoms of acute opioid ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9581440/

NSS-Bridge Device for Post-Cesarean Delivery Analgesia The purpose of this study was to test the feasibility and acceptability of a trial protocol designed to assess the effectiveness of the NSS2-Bridge device.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03555266

NSS-2 BRIDGE Device in Post-Operative Pain Management The use of the NSS-2 BRIDGE device has been demonstrated to provide significant analgesia in patients with abdominal pain syndrome.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7110792/

Auricular neural stimulation as a new non-invasive treatment ... For instance, it has been reported that neurostimulation using the NSS-2 Bridge device for 30 min resulted in at least 30% alleviation of ...

6. fda.gov fda.gov/news-events/press-announcements/fda-grants-marketing-authorization-first-device-use-helping-reduce-symptoms-opioid-withdrawal

FDA grants marketing authorization of the first device for ... FDA's granting of the current request for the NSS-2 Bridge expands the use of the device as an aid to reduce the symptoms of opioid withdrawal.

7. frontiersin.org frontiersin.org/journals/psychiatry/articles/10.3389/fpsyt.2025.1510428/full

A randomized, sham-controlled clinical trial to evaluate the ... The NET Device is effective, safe and well-tolerated for reducing opioid withdrawal symptoms. This device received FDA market clearance in May 2024.