Exenatide for Cocaine Use Disorder

Overseen By Adetola Vaughan, MA

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Christopher Verrico

Must not be taking: Opioids, Oxycodone, others

Disqualifiers: Diabetes, Severe cardiovascular, Severe gastrointestinal, others

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 6

Duration: 6 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether exenatide, a drug approved for type 2 diabetes, is safe and effective for individuals with cocaine use disorder. The researchers aim to understand how the drug interacts with cocaine and influences its use and related experiences. Participants will receive either exenatide injections or a placebo for six weeks. The trial seeks individuals who have used cocaine for at least 10 years and consume it regularly (at least 2 grams a week). As a Phase 1 trial, the research focuses on understanding how the treatment works in people.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications, but it excludes those whose medications might interact with cocaine or exenatide, or otherwise compromise safety. It's best to discuss your current medications with the study team to see if they might be an issue.

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

Research shows that exenatide, a drug typically used for type 2 diabetes, is being tested to help with cocaine addiction. Studies have found that people generally tolerate the medication well, with no unexpected or serious side effects reported. Although exenatide is not yet approved for treating cocaine addiction, its approval for diabetes indicates it is considered safe for use. This suggests that most people can use it without major problems. ^{1 2 3 4 5}

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

Unlike the standard treatments for cocaine use disorder, which primarily focus on behavioral therapies or medications like disulfiram and topiramate to curb cravings, Exenatide is unique because it targets the physiological processes related to addiction. Exenatide is derived from a hormone that regulates insulin, potentially influencing the brain's reward system differently than existing options. Researchers are excited about its promise to address cocaine dependence through a novel mechanism, offering hope for a more effective solution by directly impacting the underlying biology of addiction.

What evidence suggests that exenatide might be an effective treatment for cocaine use disorder?

This trial will compare the effects of Exenatide with a placebo for treating cocaine use disorder. Research has shown mixed but hopeful results for using Exenatide, a drug that helps control blood sugar, in treating cocaine use disorder. Some studies suggested that Exenatide might help reduce cocaine use, while others found it did not significantly affect cocaine use or the experience of using cocaine. Exenatide is already approved for treating type 2 diabetes, demonstrating its safety for humans. Although its exact effect on cocaine use remains under investigation, early findings support further research. ^{1 2 5 6 7}

Who Is on the Research Team?

Christopher D Verrico, PhD

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with Cocaine Use Disorder. Participants must meet certain health requirements, but specific inclusion criteria are not listed. People who have conditions that could interfere with the study or pose a risk to their safety based on other medications or health issues may be excluded.

Inclusion Criteria

English-speaking

Resting pulse between 50 and 95 bpm, blood pressure (BP) between 90-150 mmHg systolic and 45-95 mmHg diastolic

Hematology and chemistry laboratory tests within reference limits (±10%), except for pancreatic tests (lipase and amylase) which must be within normal limits

Exclusion Criteria

Any laboratory test deemed clinically significant by the study physician

Substance-use disorders other than for CUD that would compromise participant well-being

Participation in a clinical trial within 30 days of admission

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive once-weekly subcutaneous injections of exenatide or placebo for 6 weeks

6 weeks

6 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Exenatide

Trial Overview The trial is testing Exenatide (Bydureon), which is normally used for type 2 diabetes, to see if it can help people with Cocaine Use Disorder by reducing cocaine's effects and desire for use. It compares Exenatide against a placebo in an inpatient setting where participants' reactions to cocaine are monitored.

How Is the Trial Designed?

Group I: Drug: Exenatide 2 mg [Bydureon] Experimental Treatment 1 Intervention

Participants will receive once-weekly subcutaneous exenatide (2 mg) injections for 6 weeks.

Group II: Drug: Placebo Placebo Group 1 Intervention

Participants will receive once-weekly subcutaneous saline (i.e., placebo) injections for 6 weeks.

Exenatide is already approved in United States, European Union for the following indications:

Approved in United States as Byetta for:

• Type 2 diabetes mellitus

Approved in United States as Bydureon for:

• Type 2 diabetes mellitus

Approved in United States as Bydureon BCise for:

• Type 2 diabetes mellitus

Approved in European Union as Byetta for:

• Type 2 diabetes mellitus

Approved in European Union as Bydureon for:

• Type 2 diabetes mellitus

Who Is Running the Clinical Trial?

Christopher Verrico

Lead Sponsor

Trials

1

Recruited

40+

Christopher D. Verrico

Lead Sponsor

Trials

2

Recruited

120+

Published Research Related to This Trial

A 52-year-old male experienced systemic hypersensitivity reactions to the GLP-1 receptor agonist exenatide after multiple injections, indicating a potential safety risk associated with this medication class.

Positive skin tests confirmed the hypersensitivity to exenatide, while liraglutide was tolerated without issues, highlighting the need for careful monitoring of patients using GLP-1 receptor agonists for adverse reactions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. Steveling, EH., Winzeler, B., Bircher, AJ.[2021]

Exenatide, a GLP-1 receptor agonist approved for type 2 diabetes, significantly reduces glycosylated hemoglobin (HbA1c) by about 1% and promotes weight loss of approximately 5.3 kg over 82 weeks, without causing hypoglycemia.

The treatment is generally safe, with a low risk of acute pancreatitis and manageable side effects like mild nausea, which led to a 6% dropout rate in clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Benefit-risk assessment of exenatide in the therapy of type 2 diabetes mellitus. Gallwitz, B.[2022]

Exenatide is an effective treatment for type 2 diabetes that helps lower blood sugar levels and HbA1c without causing hypoglycemia or requiring regular blood glucose monitoring, making it a convenient option for patients.

It not only stimulates insulin secretion and inhibits glucagon but also promotes weight loss and slows gastric emptying, which can be particularly beneficial for overweight or obese patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Medication of the month... Exenatide (Byetta) incretinomimetic in the treatment of type 2 diabetes after failure and as add-on therapy to oral agents]. Scheen, AJ., Van Gaal, LF.[2018]

Exenatide extended-release (ER) significantly improves blood sugar control and reduces body weight in patients with type 2 diabetes over 24-30 weeks, with effects maintained for up to 6 years.

It is generally well tolerated with a low risk of hypoglycemia, though common side effects include mild gastrointestinal issues and headaches, making it a convenient once-weekly treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Exenatide Extended-Release: An Updated Review of Its Use in Type 2 Diabetes Mellitus. Syed, YY., McCormack, PL.[2018]

In a study involving 13 individuals with cocaine use disorder, the GLP-1 analogue exenatide did not significantly affect cocaine self-administration or subjective feelings of euphoria and craving for cocaine compared to a placebo.

Both exenatide and cocaine independently reduced levels of GLP-1 and insulin, indicating that while exenatide did not show efficacy in altering cocaine behavior, it may still influence hormone levels related to appetite and metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Testing the effects of the GLP-1 receptor agonist exenatide on cocaine self-administration and subjective responses in humans with cocaine use disorder. Angarita, GA., Matuskey, D., Pittman, B., et al.[2022]

Exenatide is an effective treatment for type 2 diabetes, but its short plasma half-life of 2.4 hours limits its use, leading to the development of products like Byetta™ and Bydureon™.

Recent research has focused on creating long-acting formulations of exenatide through various methods, including sustained-release dosage forms and structural modifications, to enhance its clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-acting preparations of exenatide. Cai, Y., Wei, L., Ma, L., et al.[2021]

Bydureon, a long-acting formulation of exenatide, allows for once-weekly injections, significantly reducing glycated hemoglobin (HbA1c) levels while maintaining similar weight loss and better digestive tolerance compared to the original twice-daily formulation.

In clinical comparisons, Bydureon has shown greater efficacy than other glucose-lowering medications like sitagliptin and pioglitazone, without causing hypoglycemia, making it a safer option for managing type 2 diabetes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Bydureon: first once weekly GLP-1 receptor agonist (exenatide LAR)]. Scheen, AJ.[2022]

In a preliminary study involving 3 patients with cocaine use disorder, the GLP-1 receptor agonist exenatide was well tolerated and showed good compliance and satisfaction over 6 weeks of treatment.

While the results regarding cocaine use were mixed, the positive safety profile and feasibility of using exenatide suggest it could be a promising candidate for further research in treating cocaine use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study. Yammine, L., Balderas, JC., Weaver, MF., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06252623

Exenatide For Reducing the Reinforcing Effects of Cocaine This study will determine the safety and tolerability of exenatide (Bydureon®) as a pharmacotherapy for cocaine use disorder.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04941521?term=EXENATIDE&aggFilters=results:with&viewType=Table&rank=8&tab=results

Study Results | Exenatide for Treating Cocaine Use Disorder The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

3. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37579116/

Feasibility of Exenatide, a GLP-1R Agonist, for Treating ... Results for cocaine use and related clinical effects were more mixed, yet encouraging. Future empirical testing of exenatide for treating CUD ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0376871621001095

Testing the effects of the GLP-1 receptor agonist exenatide ... We did not find evidence that low dose exenatide alters cocaine self-administration or the subjective effects of cocaine in people with CUD.

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33621809/

Testing the effects of the GLP-1 receptor agonist exenatide on ... Exenatide and cocaine independently reduced levels of GLP-1 and insulin, while cocaine also reduced levels of amylin. Keywords: Addictive ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04941521?tab=results

Study Results | Exenatide for Treating Cocaine Use Disorder An unfavorable change in the health of a participant, including abnormal laboratory findings, that happens during a clinical study or within a certain amount of ...

7. reporter.nih.gov reporter.nih.gov/project-details/10573011

A Human Laboratory Study of Exenatide for Reducing ... The design of the current human clinical pharmacology study will accurately predict the potential clinical efficacy of a GLP-1R agonist for reducing COC use.