Semaglutide for Opioid Use Disorder

(SHORE Trial)

Overseen By Joji Suzuki

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Brigham and Women's Hospital

Must be taking: Buprenorphine

Must not be taking: GLP-1 agonists

Disqualifiers: Substance use disorder, Diabetes, Eating 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: 15

Duration: 12 weeks

46 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether semaglutide, a medication, can help people with opioid use disorder (OUD) by reducing their response to drug-related cues. Participants will receive weekly injections of either semaglutide or a placebo (a substance with no active medication), alongside their usual treatment, over 12 weeks. The trial focuses on individuals who have started buprenorphine treatment for OUD within the last 60 days and have maintained a stable dose. The study aims to assess the effectiveness, safety, and tolerability of semaglutide for people with OUD. As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people.

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 must continue taking buprenorphine during the study. You cannot use any GLP-1 agonist medications during the trial.

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

Research has shown that semaglutide is generally safe for patients. In a study involving over 33,000 people, those taking semaglutide had a significantly lower risk of opioid overdose compared to others, suggesting its potential safety for individuals with opioid use disorder (OUD). Additionally, newer versions of semaglutide cause fewer stomach problems, which benefits those considering this treatment. Although this trial is just beginning, these findings provide some reassurance about its safety in humans. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for opioid use disorder?

Most treatments for opioid use disorder, like methadone or buprenorphine, work by targeting opioid receptors to reduce cravings and withdrawal symptoms. But semaglutide works differently. It's a GLP-1 receptor agonist, originally used for diabetes and weight management, which might influence brain pathways involved in addiction. Researchers are excited because it offers a novel mechanism that might address addiction without relying on opioid-based treatments. Additionally, semaglutide's potential to modify appetite and reward systems could provide a unique approach to managing opioid dependency.

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

Research has shown that semaglutide might help people with opioid use disorder (OUD). Studies have linked semaglutide to a significantly lower risk of opioid overdose. Animal studies demonstrated that it also reduced cravings for opioids like heroin and fentanyl. In this trial, one group of participants will receive semaglutide, while another group will receive a placebo. These findings suggest semaglutide could effectively reduce opioid cravings and prevent overdoses in people. ^{2 3 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals starting treatment with buprenorphine for opioid use disorder. Participants will be randomly assigned to receive either semaglutide or a placebo in weekly injections over 12 weeks.

Inclusion Criteria

DSM-5 diagnosis of opioid use disorder, severe

Anticipating continuation of SL-BUP for the duration of the trial

Agreeable with study team taking over the buprenorphine prescribing for the duration of the trial

Exclusion Criteria

Psychotic disorder, active suicidality or homicidality or any psychiatric condition that impairs ability to provide informed consent

BMI < 25mg/kg2

I have been diagnosed with diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline

Baseline procedures including neurocognitive testing and initial assessments

1 week

1 visit (in-person, 3 hours)

Treatment

Participants receive weekly injections of semaglutide or placebo, with dose adjustments

12 weeks

13 visits (in-person, weekly)

Follow-up

Participants are monitored for safety and effectiveness after treatment

1 week

1 visit (in-person, 3 hours)

What Are the Treatments Tested in This Trial?

Interventions

• Semaglutide

Trial Overview

The study tests if semaglutide affects cravings and reactions to drug cues in people with opioid addiction. It's also looking at how safe and tolerable the drug is as a potential treatment option.

How Is the Trial Designed?

Group I: Semaglutide Experimental Treatment 1 Intervention

This arm will receive semaglutide (n=23). All participants will initially receive 0.25mg for 4 weeks, and then as tolerated dose will be increased to 0.5mg for 4 weeks. Then as tolerated, the dose will be increased to 1.0mg for 4 weeks.

Group II: Placebo Placebo Group 1 Intervention

This arm will receive saline placebo (n=23).

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?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Published Research Related to This Trial

Semaglutide (Ozempic®) is a new subcutaneous treatment for type 2 diabetes that effectively lowers blood glucose levels by stimulating insulin release and also helps reduce body weight.

The once-weekly injection has been approved in the US, Puerto Rico, and Canada, and is also under review in other countries, with ongoing clinical development for additional conditions like obesity and liver diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide: First Global Approval. Dhillon, S.[2019]

Semaglutide (Ozempic®) is an effective once-weekly treatment for type 2 diabetes, showing superior glucose-lowering effects and greater weight loss compared to other GLP-1 receptor agonists in Phase III clinical trials.

It is approved for use in Belgium for patients with type 2 diabetes who have not achieved adequate control with other antidiabetic therapies, particularly in those with a body mass index of 30 kg/m² or higher.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Semaglutide, once weekly GLP-1 receptor agonist (Ozempic®)]. Scheen, AJ.[2019]

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]

Semaglutide, marketed as Rybelsus, is the first oral glucagon-like peptide receptor agonist approved by the FDA in 2019 for treating type 2 diabetes, highlighting its innovative delivery method.

This medication, taken once daily, aids in glucose control and weight management, potentially leading to improved health outcomes for individuals with type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Semaglutide Is a New Once-Daily Oral Medication to Treat Type 2 Diabetes. Blakely, KK., Weaver, K.[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]

Oral semaglutide (Rybelsus®) has been shown to provide better glycaemic control and promote weight loss in patients with type 2 diabetes (T2DM) compared to standard oral glucose-lowering medications, based on data from the PIONEER clinical trial program involving 9543 patients.

The safety profile of oral semaglutide is similar to other GLP-1 receptor agonists, and it demonstrated cardiovascular safety comparable to placebo in high-risk patients, making it a viable option for T2DM management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Oral semaglutide, first oral GLP-1 receptor agonist (Rybelsus®)]. Paquot, N.[2022]

Over 2 million Americans have opioid use disorder, which is partly due to overprescribing, highlighting the need for better opioid stewardship and management strategies by physicians.

Three FDA-approved medications—methadone, buprenorphine, and naltrexone—are effective for treating opioid use disorder, but successful outcomes are best achieved through comprehensive, interprofessional management plans rather than relying solely on medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prescription Drug and Alcohol Use Disorders: Opioid Use Disorder. Witt, L., Butler, F.[2019]

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]

Semaglutide, a GLP-1 receptor agonist for type 2 diabetes, has a good safety profile but is associated with a high prevalence of gastrointestinal disorders, reported in over 3500 cases (53.2%).

Compared to other diabetes medications like sitagliptin and empagliflozin, semaglutide has a significantly higher number of reported gastrointestinal adverse events, indicating the need for careful monitoring in certain patient subgroups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gastrointestinal disorders potentially associated with Semaglutide: an analysis from the Eudravigilance Database. Cabral Lopes, A., Roque, F., Lourenço, O., et al.[2023]

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]

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NCT06639464 | Semaglutide for Helping Opioid Recovery

Participants will also complete an assessment of adverse events and questionnaires probing secondary outcomes (i.e. anxiety and depression, suicidality, ...