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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Opiate Substitution Treatment, Opioid-Related Disorders

Intervention / Treatment
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* Drug: Liraglutide Pen Injector
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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-stated 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational group<br>Participants randomized to liraglutide will be started at a low dose (0.6 mg once per day) which will be gradually increased until 1.8 mg/day is reached for the 3-dose intervention and 3 mg/day is reached for the 5-dose intervention. Liraglutide will be administered by injection pen. | Drug: Liraglutide Pen Injector<br>* Liraglutide will be provided using an injection pen provided by the manufacturer<br>* Other names: Saxenda;|
| Placebo Comparator: Control group<br>Participants in the control group will have placebo administered by injection pen following the same low dose titration to 3.0 mg once per day. | Drug: Placebo<br>* Placebo injection pen<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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]) | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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]) | 
| 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]) | 
| 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]) | 
| 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]) | 
| 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]) | 
| Fasting blood samples for fructosamine | Fructosamine is measured in mmol/L | Days 2 and 19 (and additionally at Day 31 for 5-dose intervention] | 
| Fasting blood samples for A1c | A1c is measured in mmol/mol | Days 2 and 19 (and additionally at Day 31 for 5-dose intervention] | 
| 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]). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opiate treatment, Opioid treatment, Glucagon-Like Peptide-1 Agonist, Opioid use disorder, Liraglutide