Semaglutide for Opioid Addiction

Recruiting at 2 trial locations

Overseen By Jennifer Nyland, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Patricia Sue Grigson

Must be taking: Buprenorphine, Methadone

Must not be taking: GLP-1R agonists, DPP-4 inhibitors

Disqualifiers: Diabetes, Cardiovascular disease, Psychiatric disorders, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 16

Duration: 12 weeks

200 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if semaglutide (also known as Ozempic, Wegovy, or Rybelsus) can help reduce illegal opioid use in adults receiving outpatient treatment for opioid addiction. Participants will receive either semaglutide or a placebo (a treatment with no active drug) once a week for 12 weeks. Eligible participants should currently be undergoing treatment with buprenorphine or methadone and still show signs of opioid use, such as positive urine tests. As a Phase 2 trial, this research focuses on measuring semaglutide's effectiveness in an initial, smaller group, offering a chance to contribute to important findings in opioid addiction 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 using certain medications like GLP-1R agonists, DPP-4 inhibitors, or have used Sincalide, Sulfonylureas, insulin, or similar medications in the past 30 days.

Is there any evidence suggesting that semaglutide is likely to be safe for humans?

Research has shown that semaglutide is generally safe for people. In one study with over 33,000 participants, those taking semaglutide had a much lower risk of opioid overdose compared to those who didn't take it, suggesting it is safe to use alongside treatments for opioid addiction.

Another study found that semaglutide helped reduce alcohol cravings, indicating it might be safe and effective for treating addiction-related cravings. Additionally, a study of over 200,000 patients using diabetes medications, including semaglutide, showed a 32% lower risk of medical problems, further suggesting its general safety.

While specific data on side effects for people with opioid use disorder is lacking, semaglutide's use in other conditions suggests it is relatively safe. However, as this is a Phase 2 trial, more safety data will be collected to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about semaglutide for opioid addiction because it offers a fresh approach compared to traditional treatments like methadone or buprenorphine, which primarily work by interacting with opioid receptors. Semaglutide, originally developed for diabetes and weight management, works differently by mimicking the hormone GLP-1, which can influence brain pathways related to addiction. This new mechanism of action could potentially reduce cravings and support recovery in a novel way. Additionally, the once-weekly administration of semaglutide is convenient and could improve adherence for individuals seeking treatment.

What evidence suggests that semaglutide might be an effective treatment for opioid addiction?

Research has shown that semaglutide, a drug often used for diabetes, might help with opioid addiction. One study found that people with opioid addiction who took semaglutide had a 40% lower chance of overdosing on opioids. Another study reported a reduced risk of opioid overdose over a year for those using semaglutide. These findings suggest that semaglutide could lower opioid use and related dangers. In this trial, participants in the investigational group will receive semaglutide, while those in the control group will receive a placebo. Although its use for addiction treatment is still under investigation, early results appear promising. ^{6 7 8 9 10}

Who Is on the Research Team?

Jennifer Nyland, PhD

Principal Investigator

Milton S. Hershey Medical Center

Are You a Good Fit for This Trial?

This trial is for adults in outpatient treatment for opioid use disorder who are currently on buprenorphine or methadone. Participants must be willing to take weekly injections, attend regular clinic visits for drug screening and health checks, and complete mental health assessments.

Inclusion Criteria

Current diagnosis of Diagnostic and Statistical Manual Diploma in Social Medicine (DSM)-5 Opioid Use Disorder (OUD) as per the Mini International Neuropsychiatric Interview (MINI) or per the site clinic diagnosis

Able to read and communicate in English to the level required to accept standard care and complete all study requirements

I am not pregnant or breastfeeding and agree to use birth control or abstain from sex during the study.

Exclusion Criteria

Previous randomization for participation in this trial

Any other condition at screening that precludes safe participation in the trial in the judgment of the site PI or study physician

I have or had severe stomach or digestive problems.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

1 visit (in-person)

Baseline

Participants complete a baseline evaluation and are randomly assigned to semaglutide or placebo control arms

1 week

1 visit (in-person)

Treatment

Participants receive semaglutide or placebo once per week for 12 weeks, with weekly clinic visits for urine drug screening, pregnancy testing, vital signs, and questionnaires

12 weeks

12 visits (in-person)

Wash-out

Participants discontinue semaglutide or placebo and are observed for an additional week

1 week

1 visit (in-person)

Follow-up

A final follow-up visit takes place 5 weeks after the last treatment visit to monitor safety and effectiveness

5 weeks

1 visit (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Semaglutide

Trial Overview

The study tests if semaglutide can help people stop using illicit opioids compared to a placebo. It involves weekly injections of either the medication or placebo over 12 weeks, with regular monitoring through urine tests and questionnaires.

How Is the Trial Designed?

Group I: Investigational group Experimental Treatment 1 Intervention

Participants randomized to semaglutide will be started at a low dose (0.25 mg once per week) which will be gradually increased weekly until 1.0 mg is reached at Week 4 of the intervention.

Group II: Control group Placebo Group 1 Intervention

Participants in the control group will have placebo administered once per week.

Semaglutide is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in United States as Wegovy for:

• Obesity

Approved in United States as Rybelsus for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

Patricia Sue Grigson

Lead Sponsor

Trials

1

Recruited

200+

Milton S. Hershey Medical Center

Lead Sponsor

Trials

515

Recruited

2,873,000+

National Institute on Drug Abuse (NIDA)

Collaborator

Trials

2,658

Recruited

3,409,000+

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

New York University

Collaborator

Trials

249

Recruited

229,000+

Published Research Related to This Trial

The study found that the GLP-1 analog liraglutide, when administered acutely, effectively reduced heroin-seeking behavior in rats exposed to drug cues, stress, and the drug itself, suggesting its potential as a nonopioid treatment option.

Liraglutide did not impair locomotor function, indicating that its effectiveness in reducing drug-seeking behavior is not due to decreased physical performance, which supports its safety as a treatment bridge for opioid addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats. Douton, JE., Acharya, NK., Stoltzfus, B., et al.[2023]

Cebranopadol, a non-selective opioid agonist, effectively reduced cocaine self-administration in rats without affecting the consumption of saccharin, indicating its specific action against cocaine addiction.

The drug maintained its effectiveness over a 7-day treatment period without developing tolerance, and its action was confirmed to involve both nociceptin opioid and mu opioid receptors, making it a promising candidate for treating cocaine addiction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cebranopadol, a Mixed Opioid Agonist, Reduces Cocaine Self-administration through Nociceptin Opioid and Mu Opioid Receptors. Shen, Q., Deng, Y., Ciccocioppo, R., et al.[2020]

In a rodent model, the glucagon-like peptide-1 receptor agonist (GLP-1RA) liraglutide effectively reduced both cue-induced and drug-induced heroin seeking behaviors, suggesting its potential as a treatment to prevent relapse in opioid use disorder.

The titration regimen of liraglutide did not affect glucose or insulin levels, indicating that it may provide a non-opioid option for relapse prevention without the common side effects associated with other treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dose titration with the glucagon-like peptide-1 agonist, liraglutide, reduces cue- and drug-induced heroin seeking in high drug-taking rats. Evans, B., Stoltzfus, B., Acharya, N., et al.[2023]

Liraglutide, a glucagon-like peptide-1 agonist, not only reduces heroin-seeking behavior in rats but also improves sleep quality by increasing non-rapid eye movement (NREM) sleep, particularly at doses of 0.10 and 0.30 mg/kg.

The study found that liraglutide decreased wakefulness and altered sleep patterns in a dose-dependent manner, suggesting its potential dual benefit in addressing both opioid use disorders and sleep disturbances.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sleep is increased by liraglutide, a glucagon-like peptide-1 receptor agonist, in rats. Fang, J., Miller, P., Grigson, PS.[2022]

In the SUMMIT-07 trial involving 610 patients with chronic low back pain, NKTR-181 (oxycodegol) demonstrated a low incidence of opioid withdrawal symptoms, with no moderate withdrawal cases observed among participants.

The study indicated that NKTR-181 has a favorable safety profile regarding withdrawal, as only a small percentage of patients experienced mild withdrawal symptoms, suggesting it may be a safer alternative for pain management compared to traditional opioids.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Measuring Opioid Withdrawal in a Phase 3 Study of a New Analgesic, NKTR-181 (Oxycodegol), in Patients with Moderate to Severe Chronic Low Back Pain. Henningfield, JE., Gudin, J., Rauck, R., et al.[2021]

Acute treatment with the GLP-1 receptor agonist, liraglutide, significantly reduced both cue-induced and drug-induced seeking behavior for fentanyl in rats, suggesting its potential as a non-opioid treatment for Opioid Use Disorder (OUD).

The efficacy of liraglutide in reducing fentanyl seeking was comparable to that of buprenorphine, a currently approved partial opioid agonist, indicating that GLP-1 may be a promising new target for OUD therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Acute treatment with the glucagon-like peptide-1 receptor agonist, liraglutide, reduces cue- and drug-induced fentanyl seeking in rats. Urbanik, LA., Acharya, NK., Grigson, PS.[2022]

Current opioid analgesics, while effective for pain relief, have serious side effects and risks of abuse, highlighting the need for safer alternatives.

Promising non-opioid targets, such as orexin-1 receptor antagonists and nerve growth factor inhibitors, show potential in preclinical studies, but further research in non-human primates is essential to bridge the gap before clinical trials can begin.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential therapeutic targets for the treatment of opioid abuse and pain. Kiguchi, N., Ko, MC.[2022]

GLP-1 receptor (GLP-1R) agonists show promise as a new treatment for opioid use disorder (OUD), potentially helping to prevent relapse, which is a major challenge in current OUD therapies.

A novel dual agonist that targets both GLP-1Rs and neuropeptide Y2 receptors (Y2Rs) has been found to reduce fentanyl use in rats without the adverse effects seen with GLP-1R agonists alone, suggesting a more effective treatment strategy for OUD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel approach to treating opioid use disorders: Dual agonists of glucagon-like peptide-1 receptors and neuropeptide Y2 receptors. Merkel, R., Moreno, A., Zhang, Y., et al.[2022]

Opioid Use Disorder (OUD) is a growing crisis in the U.S., with opioid-related overdoses becoming the leading cause of death for individuals aged 25 to 64, highlighting the urgent need for effective treatments.

Current FDA-approved medications for OUD, including mu-opioid receptor (MOR) agonists and antagonists, have limitations such as abuse potential and adverse effects, indicating a need for new drug designs that can better target MOR with fewer risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

IUPHAR review: Recent progress in the development of Mu opioid receptor modulators to treat opioid use disorders. Pagare, PP., Flammia, R., Zhang, Y.[2023]

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