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

Phase 1

Completed

Conditions: Opiate Substitution Treatment
Opioid-Related Disorders

Interventions: Drug: Placebo
Drug: Liraglutide Pen Injector

Registration Number: NCT04199728

Lead Sponsor: Milton S. Hershey Medical Center

Brief 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.

Detailed 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 & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 27

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 Ecology Momentary Assessment (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) <30 mL/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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group	Placebo	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.
Investigational group	Liraglutide Pen Injector	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.

Primary Outcome Measures

Name	Time	Method
Change in Self-reported Cue-elicited Drug Craving as Measured by Visual Analog Scale (VAS)	Baseline (Day 1), End of the target drug dose (Day 19)	Scores are measured on a 0-100 point VAS, where 0= no craving, 100= maximum craving.
Change in Ambient Drug Craving Over Time as Measured by Visual Analog Scale (VAS)	Baseline (Day 1), Treatment Days (Days 2-19)	Scores are measured on a 0-4 point VAS, where 0= no craving, 4= maximum craving.

Secondary Outcome Measures

Name	Time	Method
Change in Blood Pressure	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)	Blood pressure measurements in mmHg. Both systolic and diastolic pressures will be assessed during the study period.
Change in Heart Rate	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)	Heart rate measurements in beats per minute.
Change in Respiratory Rate	Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)	Respiratory rate in breaths per minute.
Absolute Change in Body Weight	From Day 1 to Day 19	Body weight will be measured in kilograms (kg).
Percent Change in Body Weight	From Day 1 to Day 19	Body weight will be measured in kilograms (kg) and change will measured in %.
Change in Fasting Blood Samples for Fructosamine	From Day 2 to Day 19	Fructosamine is measured in umol/L
Change in Fasting Blood Samples for HA1c	From Day 2 to Day 19	HA1c is measured in %
Frequency of Adverse Events (AE) and Serious Adverse Events (SAE)	Days 1-21 and at 30 days post-intervention (Day 49).	Number of participants affected by probable drug-related adverse events.