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

44 Participants Needed

Trial Summary

What is the purpose of this trial?

This study will determine the safety and tolerability of exenatide (Bydureon®) as a pharmacotherapy for cocaine use disorder. An inpatient human laboratory study will be conducted in which the self-administration of cocaine, as well as the subjective and physiological effects of cocaine, are evaluated during maintenance on placebo and exenatide. Although exenatide (Bydureon) is approved by the Food and Drug Administration (FDA) for the treatment of type 2 diabetes, it has not been approved by the FDA to treat cocaine use; therefore, it is called an investigational drug.

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.

What data supports the effectiveness of the drug Exenatide for treating cocaine use disorder?

Exenatide, a drug used for type 2 diabetes, has shown promise in reducing cocaine use in preclinical studies with animals. In a small human study, it was well-tolerated and showed encouraging results, suggesting it may help reduce cocaine use, but more research is needed. ^{1 2 3 4 5}

Is exenatide safe for human use?

Exenatide has been used safely in humans for type 2 diabetes, with common side effects including nausea and antibody formation. Some people may experience allergic reactions, but these are rare. In a small study for cocaine use disorder, it was well tolerated without severe adverse events. ^{1 3 4 6 7}

How is the drug exenatide unique for treating cocaine use disorder?

Exenatide is unique for treating cocaine use disorder because it is a GLP-1 receptor agonist, originally used for type 2 diabetes, and is administered as a once-weekly injection, which may help with medication adherence. Unlike other treatments, it has shown promise in reducing cocaine use in preclinical studies, although it has not yet been proven effective in humans. ^{1 2 4 7 8}

Research Team

Christopher D Verrico, PhD

Principal Investigator

Baylor College of Medicine

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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 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]

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]

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]

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]

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 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]

References

1. Netherlands pubmed.ncbi.nlm.nih.gov

Feasibility of Exenatide, a GLP-1R Agonist, for Treating Cocaine Use Disorder: A Case Series Study. [2023]

2. Ireland 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. [2022]

3. Belgium 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]. [2018]

4. Belgium pubmed.ncbi.nlm.nih.gov

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

5. New Zealand pubmed.ncbi.nlm.nih.gov

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

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

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

Systemic Allergic Reaction to the GLP-1 Receptor Agonist Exenatide. [2021]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Long-acting preparations of exenatide. [2021]