Semaglutide for Opioid Addiction

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Jennifer Nyland, PhD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

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

Approved in 6 Jurisdictions

Trial Summary

What is the purpose of this trial?

The goal of this clinical trial is to learn if semaglutide can reduce illicit opioid use in adults in outpatient treatment for opioid use disorder, and who are receiving either buprenorphine or methadone maintenance treatment. The main question it aims to answer is: • Does semaglutide increase the likelihood that participants will refrain from using illicit and nonprescribed opioids? The investigators will compare semaglutide to a placebo (a needle prick that contains no drug) to see if semaglutide works to reduce use of illicit and nonprescribed opioids. The participants will: * Take semaglutide or a placebo every week for 12 weeks * Visit the clinic every week for urine drug screening and pregnancy testing, vital signs, and to complete mental health and drug use questionnaires * Complete smartphone surveys sent at set times during the study

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.

What evidence supports the effectiveness of the drug Semaglutide for treating opioid addiction?

Research suggests that drugs similar to Semaglutide, which are glucagon-like peptide-1 receptor agonists (GLP-1RAs), can reduce drug-seeking behavior in animal models of opioid addiction. These findings indicate that GLP-1RAs might help prevent relapse in opioid use disorder. ^{1 2 3 4 5}

How does the drug Semaglutide differ from other treatments for opioid addiction?

Semaglutide, known for its use in diabetes and weight management, is unique for opioid addiction treatment as it works through the glucagon-like peptide-1 (GLP-1) receptor, a non-opioid pathway, potentially reducing drug-seeking behavior without the risk of opioid-related side effects. ^{5 6 7 8 9}

Research Team

Jennifer Nyland, PhD

Principal Investigator

Milton S. Hershey Medical Center

Eligibility Criteria

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

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

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

Exclusion Criteria

I have type 2 diabetes or am currently using DPP-4 inhibitors.

I have severe liver disease or have had a liver transplant.

Previous randomization for participation in this trial

Trial Timeline

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)

Treatment Details

Interventions

• Placebo (Medication)
• Semaglutide (GLP-1R Agonist)

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.

Participant Groups

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 Canada, Japan for the following indications:

Approved in Canada as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

Approved in Japan as Ozempic for:

• Type 2 diabetes
• Cardiovascular disease
• Obesity

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+

Dr. Robert Harbaugh

Milton S. Hershey Medical Center

Chief Medical Officer since 2024

MD from Penn State College of Medicine

Don McKenna

Milton S. Hershey Medical Center

Chief Executive Officer since 2024

Master’s in Public Administration and Bachelor of Science in Business Administration and Marketing from Long Island 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

University of Maryland

Collaborator

Trials

171

Recruited

325,000+

Mr. Pearson

University of Maryland

Chief Executive Officer since 2019

B.S. in Business Administration from the University of Delaware, B.S. in Accounting from the University of Maryland University College, M.S. in Finance from Loyola University

Dr. Stuart McIntosh

University of Maryland

Chief Medical Officer

MD

New York University

Collaborator

Trials

249

Recruited

229,000+

Dr. Fritz François

New York University

Chief Medical Officer

MD from NYU Grossman School of Medicine

Dr. Robert I. Grossman

New York University

Chief Executive Officer since 2007

MD from NYU Grossman School of Medicine

Findings from Research

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]

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]

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]

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]

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]

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]

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]

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]

References

1. England 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. [2021]

2. United States 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. [2023]

3. United States 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. [2022]

4. Netherlands pubmed.ncbi.nlm.nih.gov

IUPHAR review: Recent progress in the development of Mu opioid receptor modulators to treat opioid use disorders. [2023]

5. United States 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. [2022]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Cebranopadol, a Mixed Opioid Agonist, Reduces Cocaine Self-administration through Nociceptin Opioid and Mu Opioid Receptors. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Acute glucagon-like peptide-1 receptor agonist liraglutide prevents cue-, stress-, and drug-induced heroin-seeking in rats. [2023]

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

Sleep is increased by liraglutide, a glucagon-like peptide-1 receptor agonist, in rats. [2022]

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

Potential therapeutic targets for the treatment of opioid abuse and pain. [2022]