Use of a GLP-1R Agonist to Treat Opioid Use Disorder

Opioid-Related Disorders Clinical Trial

Official title:

Use of a GLP-1R Agonist to Treat Opioid Use Disorder

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04199728
• Other study ID #: 13559
• Secondary ID: 1UG3DA050325-01
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 18, 2021
• Est. completion date: September 13, 2023

Study information

• Verified date: March 2024
• Source: Milton S. Hershey Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This research is being done to find out if liraglutide (brand name is Saxenda®) can safely and effectively reduce craving for opioids in patients with opioid use disorder, a primary factor contributing to early relapse.

Description:

The rationale for the proposed research is to develop an acute intervention that can improve treatment outcomes in opioid use disorder (OUD) by reducing craving, a primary factor contributing to early relapse. Although liraglutide was approved for human use in 2010, there are no data testing the effectiveness in patients with an OUD. The objective of the proposed research is to test whether treatment with a GLP-1R agonist can reduce craving in humans with OUD. Understanding how a 'satiety' agent may affect craving and brain responses to drug cues in an OUD population would provide entirely novel information. If liraglutide shows a trend towards efficacy, and safety of the GLP-1R agonist is demonstrated in this population, it would provide an indication to run the second phase, multi-center clinical trial of GLP-1R agonist in OUD patients.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 27
• Est. completion date: September 13, 2023
• Est. primary completion date: September 13, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

• Age 18 to 75 years

• Diagnosed with an OUD seeking treatment at Caron Treatment Centers (CaronTC) and planning on being enrolled in a residential treatment plan for a minimum of 4 weeks

• Women of childbearing potential must consent to use a medically accepted method of birth control or to abstain from sexual intercourse while in the study

• Able and willing to provide informed consent prior to any study-related activities

• Must be able to read and communicate in English sufficiently to complete all study requirements, including EMA

Exclusion Criteria:

• Age < 18 or > 75 years

• Women who are pregnant, planning pregnancy, breastfeeding, or unwilling to use adequate contraceptive measures

• History of angioedema, serious hypersensitivity reaction, or anaphylactic reaction to liraglutide or another glucagon-like peptide-1 receptor (GLP1R) agonist

• Personal or family history of medullary thyroid carcinoma (MTC) or patients with multiple endocrine neoplasia syndrome type 2 (MEN 2) or thyroid nodule

• Type I diabetes or history of diabetic ketoacidosis

• Type II diabetes mellitus

• Hypoglycemia on intake visit (blood glucose < 70 mg/dL)

• End-stage renal failure on dialysis or glomerular filtration rate (GFR) <30mL/min per 1.73 square meters or previous renal transplant

• Severe hepatic impairment (AST or ALT levels > 3 times upper limit of normal range) or previous liver transplant

• Current or past diagnosis of pancreatitis, gastroparesis, or other severe gastrointestinal disease

• Current or past diagnosis of gallbladder disease or gallstones

• Serious cardiovascular disease within the past 6 months (e.g. uncontrolled hypertension, heart failure, significant cardiac arrhythmias, myocardial infarction, presence of angina pectoris, symptomatic coronary artery disease, deep vein thrombosis, pulmonary embolism, second- or third-degree heart block, mitral valve or aortic stenosis, hypertrophic cardiomyopathy, stroke)

• Severe co-occurring psychiatric disorder (e.g., bipolar disorder, psychotic disorder, schizophrenia) that would, in the opinion of the Principle Investigator or study physician, interfere with participating in the study, such as if the patient needs a higher or different level of care and is going to be transferred out of Caron.

• Suicidal ideation within the past 1 month, or history of suicide attempts within the past 1 year, unless participation is cleared by clinician assessment and/or judgement.

• Treatment with any investigational drug in the one-month preceding the study

• Previous randomization for participation in this trial

• Abnormal physical exam findings, vital signs (blood pressure, heart rate, respiratory rate, body temperature), EKG measurements, and safety lab values that are deemed clinically significant by study physician

Related Conditions & MeSH terms

• Opiate Substitution Treatment
• Opioid-Related Disorders

Intervention

Drug:
• Liraglutide Pen Injector
Liraglutide will be provided using an injection pen provided by the manufacturer
• Placebo
Placebo injection pen

Locations

Country	Name	City	State
United States	Penn State Milton S Hershey Medical Center	Hershey	Pennsylvania

Sponsors (3)

Lead Sponsor	Collaborator
Milton S. Hershey Medical Center	National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in blood oxygenation level response to visual opioid drug cues in prefrontal cortex using Functional Near Infrared Spectroscopy (fNIRs)	fNIRs measures regional cerebral oxygenation saturation (%).	Baseline (Day 1) to end of the target drug dose (Day 19 [additionally Day 31 for 5-dose intervention])
Other	Rebound change in ambient drug craving over time as measured by visual analog scale (VAS)	Scores are measured on a 0-100 point VAS, where 0= no craving, 100= maximum craving.	From end of rebound follow up (Day 21 [Day 33 for 5-dose intervention]) to baseline (Day 1) and to end of the target drug dose (Day 19 [Day 31 for 5-dose intervention])
Other	Rebound change in blood pressure	Blood pressure measurements in mmHg. Both pressures will be assessed during the study period.	From end of the target drug dose (Day 19 [Day 31 for 5-dose intervention]) to rebound follow up (Day 21 [Day 33 for 5-dose intervention]).
Other	Rebound change in heart rate	Heart rate measurements in beats per minute	From end of the target drug dose (Day 19 [Day 31 for 5- dose intervention]) to rebound follow up (Day 21 [Day 33 for 5-dose intervention]).
Other	Rebound change in respiratory rate	Respiratory rate in breaths per minutes.	From end of the target drug dose (Day 19 [Day 31 for 5- dose intervention]) to rebound follow up (Day 21 [Day 33 for 5-dose intervention])
Other	Long-term change in HbA1c	A1c is measured in %.	From Day 2 to end of the target drug dose (Day 19 [Day 31 for 5-dose intervention])
Other	Long-term change in fructosamine levels	Fructosamine measured in mmol/L.	From Day 2 to end of the target drug dose (Day 19 [Day 31 for 5-dose intervention])
Primary	Change in self-reported cue-elicited drug craving as measured by visual analog scale (VAS)	Scores are measured on a 0-100 point VAS, where 0= no craving, 100= maximum craving.	Baseline (Day 1), End of the target drug dose (Day 19) [and additionally until Day 31 for 5-dose intervention])
Primary	Change in ambient drug craving over time as measured by visual analog scale (VAS)	Scores are measured on a 0-100 point VAS, where 0= no craving, 100= maximum craving.	Baseline (Day 1), then four (4) times per day on the following days: Days 2-3; Days 6-9; Days 12-15; Days 18-21
Secondary	Change in blood pressure	Blood pressure measurements in mmHg. Both systolic and diastolic pressures will be assessed during the study period.	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14, 19, 20, 26, and 31); and end of rebound follow-up (Day 21 [Day 33 for 5-dose intervention])
Secondary	Change in heart rate	Heart rate measurements in beats per minute.	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14, 19, 20, 26, and 31); and end of rebound follow-up (Day 21 [Day 33 for 5-dose intervention])
Secondary	Change in respiratory rate	Respiratory rate in breaths per minute.	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14, 19, 20, 26, and 31); and end of rebound follow-up (Day 21 [Day 33 for 5-dose intervention])
Secondary	Absolute change in body weight	Body weight will be measured in kilograms (kg).	Daily, from Days 1 to 21 [Days 1- 33 for 5-dose intervention])
Secondary	Percent change in body weight	Body weight will be measured in kilograms (kg) and change will measured in %.	Daily, from Days 1 to 21 [Days 1- 33 for 5-dose intervention])
Secondary	Fasting blood samples for fructosamine	Fructosamine is measured in mmol/L	Days 2 and 19 (and additionally at Day 31 for 5-dose intervention]
Secondary	Fasting blood samples for A1c	A1c is measured in mmol/mol	Days 2 and 19 (and additionally at Day 31 for 5-dose intervention]
Secondary	Frequency of adverse events (AE) and serious adverse events (SAE)	Adverse events will only include those that are determined to be related to the study drug.	Days 1-21 [Days 1-33 for 5-dose intervention]), and at 30 days post-intervention (Day 49 [Day 61 for 5-dose intervention]).