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

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ClinicalTrials.gov Identifier: NCT03232112
Recruitment Status : Recruiting
First Posted : July 27, 2017
Last Update Posted : July 13, 2018
Sponsor:
Collaborators:
The Novavì outpatient clinics, Copenhagen
Neurobiology Research Unit, Rigshospitalet, Copenhagen
Section of Biostatistics University of Copenhagen, Copenhagen
Information provided by (Responsible Party):
Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet

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.

Condition or disease Intervention/treatment Phase
Alcohol Dependence, in Remission Addiction, Alcohol Drug: Exenatide 2 MG Injection Drug: BD PosiFlush (saline) Phase 2

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 139 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Double-blinded, randomized, placebo-controlled.
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: 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.
Primary Purpose: Treatment
Official Title: Does Glucagon-like Peptide (GLP-1) Receptor Agonist Stimulation Reduce Alcohol Intake in Patients With Alcohol Dependence?
Actual Study Start Date : July 12, 2017
Estimated Primary Completion Date : November 1, 2019
Estimated Study Completion Date : November 1, 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Active Comparator: Exenatide 2 MG Injection
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
Subcutaneous injection once-weekly
Other Name: Bydureon Pen, 2 Mg, Extended Release

Placebo Comparator: BD PosiFlush (saline)
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)
Subcutaneous injection once-weekly
Other Name: Saline




Primary Outcome Measures :
  1. Heavy drinking days [ Time Frame: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks ]
    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.


Secondary Outcome Measures :
  1. Total alcohol consumption [ Time Frame: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks ]
    Percent reduction in alcohol consumption, defined as "x" grams of alcohol for the past 30 days. This will be registered via the Timeline-Follow-Back (TLFB) method.

  2. Penn Alcohol Craving Scale (PACS) score [ Time Frame: Baseline and 26 weeks ]
    Score for measuring alcohol craving

  3. Alcohol Use Disorders Identification Test (AUDIT) score [ Time Frame: Baseline and 26 weeks ]
    Screening for excessive drinking

  4. Drug Use Disorders Identification Test (DUDIT) score [ Time Frame: Baseline and 26 weeks ]
    A parallel instrument to the AUDIT for identification of individuals with drug-related problems

  5. Screen For Cognitive Impairment in Psychiatry (SCIP) test [ Time Frame: Baseline, 4 weeks and 26 weeks ]
    The 20 minute test is a simple scale developed for screening cognitive deficits

  6. Plasma-gamma-glutamyltransferase (GGT) [ Time Frame: Baseline and 26 weeks ]
    Liver parameter

  7. Plasma-alanine aminotransferase (ALAT) [ Time Frame: Baseline and 26 weeks ]
    Liver parameter

  8. Plasma-phosphatidylethanol (PEth) [ Time Frame: Baseline, 4, 12, 20 and 26 weeks ]
    Biomarker for alcohol consumption

  9. Blood-mean cell volume [ Time Frame: Baseline and 26 weeks ]
    Measure of the average volume of a red blood cell

  10. Body weight [ Time Frame: Baseline, 4, 12, 20 and 26 weeks ]
    Body weight in kilograms

  11. Blood pressure [ Time Frame: Baseline, 4, 12, 20 and 26 weeks ]
    Systolic and diastolic blood pressure

  12. Pulse [ Time Frame: Baseline, 4, 12, 20 and 26 weeks ]
    Number of heartbeats pr. minute

  13. Waist circumference [ Time Frame: Baseline, 4, 12, 20 and 26 weeks ]
    Widest abdominal circumference in centimeters

  14. Plasma-glycemic control parameters [ Time Frame: Baseline and 26 weeks ]
    HbA1c, cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL).

  15. Kidney function [ Time Frame: Baseline and 26 weeks (eGFR also at week 12) ]
    e-GFR, urine albumine/creatinine-ratio.

  16. Short Form Health Survey (SF-36) [ Time Frame: Baseline and 26 weeks ]
    36-item, patient-reported survey of patient health

  17. Plasma amylase [ Time Frame: Baseline and 26 weeks ]
    Safety (i.e. pancreatic function)

  18. Symptom Checklist (SCL-92) [ Time Frame: Baseline and 26 weeks ]
    92-item, patient-reported survey of a broad range of psychological problems and symptoms of psychopathology.

  19. Single-photon emission computed tomography (SPECT) [ Time Frame: Baseline and 26 weeks ]
    In this study we want to investigate whereas GLP-1 receptor stimulation induces changes in the striatal dopamine transporter availability in humans.

  20. fMRI (functional magnetic resonance imaging) [ Time Frame: Baseline and 26 weeks ]
    In this study we want to investigate whereas GLP-1 treatment modulate neural responses in reward processing regions including nucleus accumbens. Data from the 25 healthy participants will be used as comparable standard when analyzing the data.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 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
  • Heavy alcohol drinking defined as having alcohol consumption over 60 g of alcohol per day (men) or 48 g of alcohol per day (women) for at least 5 days in the past 30 days prior to inclusion measured by the TLFB method.

Exclusion Criteria:

  • 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
  • No serious withdrawal symptoms at inclusion (a score higher than 9 on the Clinical Institute Withdrawal Assessment of Alcohol Scale, Revised (CIWA-Ar)) at baseline examinations
  • Present or former neurological disease including traumatic brain injury
  • Present or former diagnosis of type 1 or type 2 diabetes or plasma Haemoglobin A1c (HbA1c ) ≥48 moll/L at inclusion
  • 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)
  • Pregnancy (serum hCG > 3 at inclusion) Impaired hepatic function (liver transaminases >3 times up-per normal limit)
  • 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 against alcohol dependence including disulfiram, naltrexone, acamprosate and nalmefene or treatment with any of these compounds within 1 month prior to inclusion
  • 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
  • Only for patients undergoing brain scans: Contraindications for undergoing an fMRI scan (magnetic implants, pacemaker, claustrophobia etc.). Contraindications for undergoing a SPECT-scan (allergy towards iodine, radiation exposure, excluding background radiation but including diagnostic x-rays and other medical exposures, exceeding 10 mSv in the last 12 months)
  • Unable to speak and/or understand Danish
  • Any condition that the investigator feels would interfere with trial participation

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03232112


Contacts
Contact: Anders Fink-Jensen, MD, DMSci +45 22755843 anders.fink-jensen@regionh.dk
Contact: Mette K Klausen, MD +45 22649599 mette.kruse.klausen@regionh.dk

Locations
Denmark
Novavì ambulatorierne Recruiting
Copenhagen, Frederiksberg, Denmark, 2000
Contact: Signe W. Düring, MD       SDUR@novavi.dk   
Contact: Mette K Klausen, MD    +45 22649599    mette.kruse.klausen@regionh.dk   
Sponsors and Collaborators
Anders Fink-Jensen, MD, DMSci
The Novavì outpatient clinics, Copenhagen
Neurobiology Research Unit, Rigshospitalet, Copenhagen
Section of Biostatistics University of Copenhagen, Copenhagen
Investigators
Principal Investigator: Signe W. Düring, MD The Novavi outpatient clinics, Copenhagen

Responsible Party: Anders Fink-Jensen, MD, DMSci, Professor, MD, DMSci, Psychiatric Centre Rigshospitalet
ClinicalTrials.gov Identifier: NCT03232112     History of Changes
Other Study ID Numbers: EXALT study
First Posted: July 27, 2017    Key Record Dates
Last Update Posted: July 13, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: At the start and at the end of the study a blood sample (9ml) and a urine sample (7.2ml) will be stored in a biobank for future research. The patients will be asked to give a separate written consent. Using this biobank in the future will require a new approval from the Danish Data Protection Agency.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Keywords provided by Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet:
Alcohol
Addiction
Glucagon Like Peptide-1
GLP-1

Additional relevant MeSH terms:
Alcoholism
Behavior, Addictive
Alcohol Drinking
Compulsive Behavior
Impulsive Behavior
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Drinking Behavior
Ethanol
Exenatide
Glucagon
Calcium heparin
Heparin
Anti-Infective Agents, Local
Anti-Infective Agents
Central Nervous System Depressants
Physiological Effects of Drugs
Hypoglycemic Agents
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Gastrointestinal Agents
Anticoagulants
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action