Does Treatment With GLP-1 Reduce Alcohol Intake in Patients With Alcohol Dependence?

NCT03232112 | Completed Phase 2 DMC

• 1 other identifier: EXALT study
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 1

Brief Summary

The study is a double-blinded, randomized, placebo-controlled, 26-weeks clinical trial. The objective of the trial is to investigate the effects of the GLP-1 receptor agonist Bydureon® (exenatide) vs. placebo on alcohol intake in patients with a diagnosis of alcohol dependence.

Conditions

Alcohol Dependence, in Remission; Addiction, Alcohol

Keywords

Alcohol; Addiction; Glucagon Like Peptide-1; GLP-1

Outcome Measures

Primary Outcomes (1)

• Heavy drinking days

  Percent reduction in alcohol consumption, defined as total number of heavy drinking days (as days with an excess intake of 60/48 grams of alcohol per day (men and women, respectively)) for the past 30 days. This will be registered via the Timeline-Follow-Back (TLFB) method.

  30 days prior to baseline and 30 days prior to final follow up at 26 weeks

Secondary Outcomes (20)

• Total alcohol consumption

  30 days prior to baseline and 30 days prior to final follow up at 26 weeks

• Penn Alcohol Craving Scale (PACS) score

  Baseline and 26 weeks

• Alcohol Use Disorders Identification Test (AUDIT) score

  Baseline and 26 weeks

• Drug Use Disorders Identification Test (DUDIT) score

  Baseline and 26 weeks

• Screen For Cognitive Impairment in Psychiatry (SCIP) test

  Baseline, 4 weeks and 26 weeks

Study Arms (2)

Exenatide 2 MG Injection

ACTIVE COMPARATOR

Bydureon® (exenatide) is supplied as powder and solvent for prolonged release injection (once-weekly). Bydureon® is delivered in a carton containing four pens. Each single-dose, dual-chamber pen contains 0.65 ml of diluent and 2 mg of exenatide, which are isolated until mixed by the person administering the drug. Needles are supplied with the pen.

Drug: Exenatide 2 MG Injection

BD PosiFlush (saline)

PLACEBO COMPARATOR

The placebo will be supplied for as pre-filled saline syringes (BD PosiFlush™, BD Worldwide) containing 3 ml each. Needles are bought separately.

Drug: BD PosiFlush (saline)

Interventions

Exenatide 2 MG Injection DRUG

Subcutaneous injection once-weekly

Also known as: Bydureon Pen, 2 Mg, Extended Release

Exenatide 2 MG Injection

BD PosiFlush (saline) DRUG

Subcutaneous injection once-weekly

Also known as: Saline

BD PosiFlush (saline)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Informed oral and written consent
• Diagnosed with alcohol dependence according to the criteria of International Classification of Diseases (ICD) 10, World Health Organization and DSM-5
• Alcohol use disorder identification test (AUDIT) score \>15
• Age 18 - 70 years

You may not qualify if:

• Severe psychiatric disease, defined as a diagnosis of schizophrenia, paranoid psychosis, bipolar dis-order or mental retardation
• A history of delirium tremens or alcohol withdrawal seizures
• Present or former neurological disease including traumatic brain injury
• Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant within the next 9 months (26 weeks plus three months after discontinuation of Bydureon®) , or are not using contraceptives (during the whole study period) considered as highly effective (combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal, transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable, implantable) intrauterine device - IUD, IUS, bilateral tubal occlusion, vasectomised partner, sexual abstinence) (33)
• Impaired renal function (eGFR \< 50 ml/min and/or microalbuminuria) Impaired pancreatic function (any history of acute or chronic pancreatitis and/or amylase \> 2 times upper limit)
• S-triglycerides \> 10 mmol/l
• Former medullary thyroid carcinoma (MTC) and/or family history with MTC and/or Multiple Endo-crine Neoplasia syndrome type 2 (MEN 2)
• Cardiac problems defined as decompensated heart failure (NYHA class III or IV), unstable angina pectoris and/or myocardial infarction within the last 12 months
• Uncontrolled hypertension (systolic blood pressure \>180 mmHg, diastolic blood pressure \>110 mmHg)
• Concomitant pharmacotherapy with dopamine active drugs, such as some types of Attention Deficit Hyperactivity Disorder (ADHD) medication (methylphenidate)
• Receiving any investigational drug within the last 3 months
• Use of weight-lowering pharmacotherapy within the preceding 3 month
• Any other active substance use defined as a DUDIT-score \> 6 (for men) \>2 (for women) and fulfilling the criteria's for dependence of the substance according to the criteria of International Classification of Diseases (ICD) 10 (except nicotine)
• BMI \<18.5 kg/m2
• Hypersensitivity to the active substance or to any of the excipients

Sponsors & Collaborators

• Anders Fink-Jensen, MD, DMSci: lead
• The Novavì outpatient clinics, Copenhagen: collaborator
• Rigshospitalet, Denmark: collaborator
• University of Copenhagen: collaborator

Study Sites (1)

Novavì ambulatorierne

Copenhagen, Frederiksberg, 2000, Denmark

Location

Related Publications (1)

• Klausen MK, Jensen ME, Moller M, Le Dous N, Jensen AO, Zeeman VA, Johannsen CF, Lee A, Thomsen GK, Macoveanu J, Fisher PM, Gillum MP, Jorgensen NR, Bergmann ML, Enghusen Poulsen H, Becker U, Holst JJ, Benveniste H, Volkow ND, Vollstadt-Klein S, Miskowiak KW, Ekstrom CT, Knudsen GM, Vilsboll T, Fink-Jensen A. Exenatide once weekly for alcohol use disorder investigated in a randomized, placebo-controlled clinical trial. JCI Insight. 2022 Oct 10;7(19):e159863. doi: 10.1172/jci.insight.159863.

  PMID: 36066977 DERIVED

MeSH Terms

Conditions

Alcoholism; Behavior, Addictive

Interventions

Exenatide; Injections; Sodium Chloride

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Compulsive Behavior; Impulsive Behavior; Behavior

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors; Drug Administration Routes; Drug Therapy; Therapeutics; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Signe W. Düring, MD

  The Novavi outpatient clinics, Copenhagen

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: An un-blinded nurse will be responsible for carrying out the randomization of the patients in REDCap. When randomization is carried out, the nurse will ensure that the patient gets the treatment that he/she is allocated to. Patients, investigators, other care givers performing assessments and persons performing data analysis will remain blinded from the time of randomization until time of database unlock. In order to maintain the blinding of the patients, the nurse will prepare the injection in a separate room and the patients will be blindfolded as the injection is given.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, MD, DMSci

Model Details: Double-blinded, randomized, placebo-controlled.

Study Record Dates

• First Submitted: July 20, 2017
• First Posted: July 27, 2017
• Study Start: August 7, 2017
• Primary Completion: March 15, 2020
• Study Completion: October 5, 2020
• Last Updated: June 4, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will share

Locations

DK (1)