Clinical trial NCT04199728: Use of a GLP-1R Agonist to Treat Opioid Use Disorder
Official title: Use of a GLP-1R Agonist to Treat Opioid Use Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Opiate Substitution Treatment
Opioid-Related Disorders
Keywords: Opiate treatment
Opioid treatment
Glucagon-Like Peptide-1 Agonist
Opioid use disorder
Liraglutide
Lead sponsor: Milton S. Hershey Medical Center
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Drug Abuse (NIDA)
First posted: 2019-12-16
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Change in Self-reported Cue-elicited Drug Craving as Measured by Visual Analog Scale (VAS)
timeFrame: Baseline (Day 1), End of the target drug dose (Day 19)
measure: Change in Ambient Drug Craving Over Time as Measured by Visual Analog Scale (VAS)
timeFrame: Baseline (Day 1), Treatment Days (Days 2-19)
Secondary outcomes:
measure: Change in Blood Pressure
timeFrame: Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)
measure: Change in Heart Rate
timeFrame: Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)
measure: Change in Respiratory Rate
timeFrame: Baseline (Day 1); beginning of each study drug dose (Days 2, 8, 14)
measure: Absolute Change in Body Weight
timeFrame: From Day 1 to Day 19
measure: Percent Change in Body Weight
timeFrame: From Day 1 to Day 19
measure: Change in Fasting Blood Samples for Fructosamine
timeFrame: From Day 2 to Day 19
measure: Change in Fasting Blood Samples for HA1c
timeFrame: From Day 2 to Day 19
measure: Frequency of Adverse Events (AE) and Serious Adverse Events (SAE)
timeFrame: Days 1-21 and at 30 days post-intervention (Day 49).
Other outcomes:
measure: Change in Blood Oxygenation Level Response to Visual Opioid Drug Cues in Prefrontal Cortex Using Functional Near Infrared Spectroscopy (fNIRs)
timeFrame: Baseline (Day 1), end of the target drug dose (Day 19)
measure: Rebound Change in Ambient Drug Craving Over Time as Measured by Visual Analog Scale (VAS)
timeFrame: Treatment (averaged across Days 2-19), Rebound follow up (averaged across Days 20-21)
measure: Rebound Change in Blood Pressure
timeFrame: From end of the target drug dose (Day 19) to rebound follow up (Day 21).
measure: Rebound Change in Heart Rate
timeFrame: From end of the target drug dose (Day 19) to rebound follow up (Day 21).
measure: Rebound Change in Respiratory Rate
timeFrame: From end of the target drug dose (Day 19) to rebound follow up (Day 21).
Locations:
city: Hershey
country: United States
facility: Penn State Milton S Hershey Medical Center
state: Pennsylvania
Study officials:
affiliation: Milton S. Hershey Medical Center
name: Scott Bunce, PhD
role: PRINCIPAL_INVESTIGATOR
References: