Opioid Withdrawal Management for Opioid Use Disorder

Recruiting at 1 trial location

Overseen By Kelly E Dunn, PhD, MBA

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of Maryland, Baltimore

Must not be taking: Methadone, Buprenorphine, Alcohol, Benzodiazepines

Disqualifiers: Pregnancy, Hypotension, Bradycardia, Myocardial infarction, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 1

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to understand how individuals with opioid use disorder experience withdrawal symptoms during a medication taper. It tests lofexidine (also known as BritLofex or Lucemyra) alone and in combination with naloxone to help manage withdrawal. Participants will follow a specific plan that includes medication stabilization, withdrawal challenges, and transition to aftercare. Individuals who currently use opioids, show signs of physical dependence, and wish to taper off opioids might be suitable candidates. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important findings.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, if you are on methadone or buprenorphine maintenance treatment, you cannot participate in the trial.

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

Research has shown that lofexidine is generally safe and effective for managing symptoms during opioid withdrawal. The FDA has approved it for this use, indicating it has passed several safety tests. Studies have found that lofexidine reduces withdrawal symptoms more effectively than a placebo, which contains no active medicine.

When combined with naloxone, lofexidine is known to safely ease withdrawal symptoms. Naloxone, often used to reverse overdoses, is also considered safe, especially under medical supervision.

While these treatments are usually well-tolerated, they can have side effects. It is important to consult a healthcare provider to determine if they are appropriate. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments for opioid withdrawal management because they offer unique approaches to easing the withdrawal process. Lofexidine is notable for its ability to reduce withdrawal symptoms without being addictive, unlike traditional opioid-based therapies. Additionally, combining Naloxone with Lofexidine may enhance the effectiveness in managing withdrawal by not only blocking opioid effects but also easing withdrawal symptoms, offering a potentially more comprehensive solution for those with opioid use disorder. This approach could provide a safer and potentially faster path to recovery compared to existing treatments.

What evidence suggests that these treatments might be effective for opioid use disorder?

Research has shown that lofexidine helps manage symptoms when someone stops using opioids. Studies have found that it reduces withdrawal symptoms more effectively than a placebo and is generally safe and well-tolerated. Lofexidine works as well as other treatments like diazepam and clonidine. In this trial, participants will receive a lofexidine-assisted taper. When combined with naloxone, a drug that reverses opioid overdoses, lofexidine may offer additional support during withdrawal. Overall, lofexidine is known for easing withdrawal symptoms and helping people remain in treatment. ^{1 2 4 6 7}

Who Is on the Research Team?

Kelly E Dunn, Ph.D, M.B.A.

Principal Investigator

University of Maryland

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with opioid use disorder who are physically dependent on opioids and interested in tapering off. It's not for those dependent on alcohol or benzodiazepines, pregnant or breastfeeding women, people on methadone/buprenorphine treatment, or those with significant heart issues, mental health disorders, active hepatitis B/C infections with abnormal liver tests.

Inclusion Criteria

Opioid-positive urine sample

Exclusion Criteria

Clinically significant hypotension (<90/60mmHg) or bradycardia (<45bpm)

I have hepatitis B or C, but my liver is functioning normally.

Significant mental health or physical disorder, or life circumstances, that is expected to interfere with study participation

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1-2 weeks

Morphine Stabilization

Participants are maintained on morphine for stabilization and undergo naloxone challenges to assess withdrawal symptoms

5 days

Daily monitoring

Lofexidine-assisted Taper

Participants are tapered off morphine using lofexidine to manage withdrawal symptoms

5 days

Daily monitoring

Transition to Aftercare

Participants transition to buprenorphine maintenance or receive oral naltrexone and an injection of Vivitrol

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Lofexidine
• Morphine
• Naloxone
• Naloxone + Lofexidine

Trial Overview The study is testing how different treatments affect opioid withdrawal symptoms during a medication taper. Treatments include Naloxone combined with a placebo or lofexidine (a non-opioid medication), and Morphine as comparisons to understand individual responses to withdrawal.

How Is the Trial Designed?

Group I: Within-subject design Experimental Treatment 4 Interventions

All participants will undergo the same study design, which includes hydromorphone stabilization (days 1-5), two naloxone challenges (scheduled during morphine stabilization), lofexidine-assisted taper (days 6-10), and transition to aftercare (day 11).

Lofexidine is already approved in United States, United Kingdom for the following indications:

Approved in United States as Lucemyra for:

• Mitigation of opioid withdrawal symptoms to facilitate abrupt opioid discontinuation in adults

Approved in United Kingdom as BritLofex for:

• Management of opioid withdrawal symptoms

Who Is Running the Clinical Trial?

University of Maryland, Baltimore

Lead Sponsor

Trials

729

Recruited

540,000+

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

Published Research Related to This Trial

In a case series of 17 patients undergoing inpatient treatment for opioid withdrawal, lofexidine was found to effectively reduce withdrawal symptoms, with 65% of patients showing decreased clinical opioid withdrawal scale (COWS) scores from intake to discharge.

Lofexidine was well-tolerated, with stable blood pressure and a decrease in heart rate over time, indicating its safety in a clinical setting, although barriers such as cost and accessibility remain challenges for broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine for acute opioid withdrawal: A clinical case series. Renfro, ML., Loera, LJ., Tirado, CF., et al.[2022]

In a double-blind, randomized trial involving 89 opiate-dependent patients, lofexidine combined with naloxone did not significantly improve detoxification completion rates compared to lofexidine with placebo.

Patients receiving naloxone experienced lower withdrawal levels throughout detoxification, indicating it may help manage cravings, but it did not significantly speed up the overall resolution of withdrawal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of combined naloxone/lofexidine in opiate detoxification: results from a double-blind randomized and placebo-controlled trial. Beswick, T., Best, D., Bearn, J., et al.[2016]

Lofexidine is an effective option for managing symptoms of opiate withdrawal by reducing sympathetic outflow, but it remains largely experimental in the US and Canada despite its approval in other regions since the 1980s.

The development of lofexidine has faced challenges due to market factors and regulatory considerations, but recent clinical trials are starting to rectify past oversights by exploring improved formulations and specific enantiomers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The preclinical discovery of lofexidine for the treatment of opiate addiction. Vartak, AP.[2014]

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]

Lofexidine, a non-opioid treatment for opioid withdrawal, was studied in 681 participants, showing small, temporary increases in QTcF (a measure of heart rhythm) during the first 24 hours, which resolved by Day 4.

By Day 7, QTcF levels decreased from baseline in all groups, suggesting that while lofexidine can cause transient changes in heart rhythm, it may ultimately have a stabilizing effect, likely due to its sympatholytic actions that alter autonomic tone.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of lofexidine on cardiac repolarization during treatment of opioid withdrawal. Darpö, B., Pirner, M., Longstreth, J., et al.[2020]

In a randomized controlled trial involving 80 opiate-dependent individuals, both buprenorphine/naloxone and methadone/lofexidine showed similar overall outcomes in managing opiate withdrawal symptoms and treatment retention.

However, during the induction phase, withdrawal symptoms decreased more slowly and cravings were higher in the buprenorphine/naloxone group, while methadone/lofexidine led to earlier peak withdrawal symptoms during detoxification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Buprenorphine/naloxone versus methadone and lofexidine in community stabilisation and detoxification: A randomised controlled trial of low dose short-term opiate-dependent individuals. Law, FD., Diaper, AM., Melichar, JK., et al.[2018]

Lofexidine hydrochloride (Lucemyra) is effective in managing opioid withdrawal symptoms, providing a non-opioid treatment option for individuals undergoing detoxification.

Erenumab-aooe (Aimovig) has been shown to significantly reduce the frequency of migraine attacks, offering a targeted approach to migraine prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pharmaceutical Approval Update. Choy, M.[2020]

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 (LFX) at a dose of 2.4 mg/day was found to significantly improve control over opioid cravings in individuals with opioid use disorder when combined with naltrexone (NTX), compared to a placebo group.

While LFX showed promise in enhancing treatment compliance and reducing opioid cravings, it also had a higher withdrawal rate due to medication intolerance, indicating the need for careful monitoring and potential dose adjustments in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lofexidine in Combination With Oral Naltrexone for Opioid Use Disorder Relapse Prevention: A Pilot Randomized, Double-Blind, Placebo-Controlled Study. Hermes, G., Hyman, SM., Fogelman, N., et al.[2020]

Citations

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A Comprehensive Update of Lofexidine for the Management ... Clinical Studies: Safety and Efficacy. The treatment of opioid withdrawal using lofexidine is generally safe, well-tolerated, and effective. Lofexidine is used ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6968526/

Efficacy of lofexidine for mitigating opioid withdrawal symptoms This simplified analysis confirmed previous per-protocol results, that lofexidine better reduces OWS severity and increases retention compared with placebo in ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1544319119304534

Lofexidine versus clonidine for mitigation of opioid ... One study demonstrated a statistically significant reduction in opioid withdrawal symptom severity with lofexidine compared with clonidine, whereas the other 4 ...

4. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000OtherR.pdf

209229Orig1s000 - accessdata.fda.gov ... efficacy and safety of lofexidine in subjects with opioid dependence and experiencing withdrawal. This was an 8-day study consisting of 3 ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S0376871617301874

A phase III, randomized, multi-center, double blind ... Lofexidine significantly decreased the scores on The Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study Day 5 (withdrawal Day 2) compared to placebo.

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/nda/2018/209229Orig1s000RiskR.pdf

209229Orig1s000 - accessdata.fda.gov Opioid withdrawal symptoms occur both in patients who have been using opioids appropriately, and in patients with OUD. There are no approved ...

7. pharmacy.hsc.wvu.edu pharmacy.hsc.wvu.edu/media/2958/lucemyra-lofexidine.pdf

Lucemyra Generic Name1,2,3,4: Lofexidine Manufacturer1, ... A Phase 3 placebo- controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Drug Alcohol Depend. 2008 ...