Alcohol dependence MedDRA version: 20.0 Level: LLT Classification code 10001125 Term: Addiction System Organ Class: 100000004873
Conditions
Interventions
Trade Name: Bydureon
Pharmaceutical Form: Powder and solvent for solution for injection in pre-filled pen
INN or Proposed INN: EXENATIDE
CAS Number: 141758-74-9
Concentration unit: mg milligram(s)
Con
Sponsors
Psychiatric Centre Copenhagen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Informed oral and written consent • Diagnosed with alcohol dependence according to the criteria of International Classification of Dis-eases (ICD) 10, World Health Organization and DSM-5 • Alcohol use disorder identification test (AUDIT) score >15 (29) • 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. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 110 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 59
Exclusion criteria
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 With-drawal Assessment of Alcohol Scale, Revised (CIWA-Ar)) at baseline examinations. • Present or former neurological disease including traumatic brain injury • Type 1 diabetes, type 2 diabetes or HbA1c =48 mmol/l at inclusion • Females of child bearing potential who are pregnant, breast-feeding or have intention of becoming pregnant or are not using contraceptive measures considered as highly effective (30) • Impaired hepatic function (liver transaminases >3 times upper normal limit) • Impaired renal function (se-creatinine >150 µM and/or macro albuminuria) • 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 pec-toris 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 months prior to inclusion • Concomitant pharmacotherapy with dopamine active drugs, such as some types of Attention Defi-cit Hyperactivity Disorder (ADHD) medication (methylphenidat). • 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 criterias for dependence of the substance according to the criteria of International Classifica-tion of Diseases (ICD) 10 (except nicotine) • BMI <18,5 kg/m2 • Contraindications for undergoing a fMRI scan (magnetic implants, pacemaker, claustrophobia etc.) • Contraindications for undergoing a SPECT-scan: radiation exposure, excluding background radia-tion but including diagnostic x-rays and other medical exposures, exceeding 10 mSv in the last 12 months • Allergy towards iodine. • Unable to speak and/or understand Danish • Any condition that the investigator feels would interfere with trial participation
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to investigate the effects of the GLP-1 receptor agonist Bydureon® on total number of heavy drinking days from baseline to follow up after 26 weeks of treatment in patients with alcohol dependence in a 26-weeks double-blinded, randomized placebo-controlled clinical trial. )). Furthermore, patients will be approached 26 weeks after end participation, in order to evaluate whether or not there is a long-term effect of the intervention on the TLFB questionnaire.;Secondary Objective: We also wish to explore the neuromolecular and neuroanatomical underpinnings of the potential beneficial effects of Bydureon® treatment in the brain by use of the brain imaging techniques brain single photon emission tomography (SPECT) and functional magnetic resonance imaging (fMRI).;Primary end point(s): Percent reduction in total number of heavy drinking days and defined as days with an excess intake of 60/48 grams of alcohol per day (men and women, respectively) from baseline to follow-up after 26 weeks of treatment measured by the Time Line Follow Back (TFLB) method.;Timepoint(s) of evaluation of this end point: Q4, 2020 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include changes in total alcohol consumption (g/30 days measured by TLFB), changes in number of days without alcohol consumption and Penn Alcohol Craving Scale (PACS) score, change in Alcohol Use Disorders Identification Test (AUDIT) score, Drug Use Disorders Identification Test (DUDIT) score, change in the liver parameters gamma-glutamyltransferase (GGT), alanine aminotransferase (ALAT), and phosphatidyl-ethanol (PEth). Safety will also be evaluated through measure-ments of pancreatic function (the pancreatic parameters amylase and lipase together with clinical evaluation). Other parameters will be mean cell volume (MCV), changes in body weight, blood pressure, pulse, overall glycaemic con-trol parameters (HbA1c), kidney function (p-creatinine, eGFR and urine albu-min/creatinine ratio) and measures of health (Short Form Health Survey (SF-36), life quality (The WHO-Five Well-being Index (WHO-5)) and Symptom Checklist (SCL-92)). )). Furthermore, patients will be approached 26 weeks after end participation, in order to evaluate whether or not there is a long-term effect of the intervention on the TLFB questionnaire. In addition to these clinical outcome parameters we will explore the possible neuromolecular effects by measuring striatal dopamine transporter (DAT) availability before and after administration of Bydureon® by use of the Single-photon emission computed tomography (SPECT). The possible neuroanatomical underpinnings of Bydureon® will be investigated by use of functional Magnetic Resonance Imaging (fMRI). These examinations will be performed in two subgroups of patients treated with either Bydureon® or placebo. To have comparable standard data of the alcohol related fMRI paradigm, we will include 25 healthy participants with no record of alcohol dependence. They will be matched with gender and age of the patients and undergo one fMRI scan. ;Timepoint(s) of evaluation of this end point: Changes in total alcohol | — |
Countries
Denmark
Contacts
Public ContactMette Kruse Klausen
Psychiatric Centre Copenhagen
Outcome results
None listed