Alcohol Dependence, in RemissionPhase 2EXALTNCT03232112
Does Treatment With GLP-1 Reduce Alcohol Intake in Patients With Alcohol Dependence?
A Phase 2 study testing Exenatide 2 MG Injection and BD PosiFlush (saline) in people with Alcohol Dependence, in Remission and Addiction, Alcohol, run by Anders Fink-Jensen, MD, DMSci at 1 site in Denmark.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Alcohol Dependence, in Remission, Addiction, Alcohol
- What is being tested?
- Exenatide 2 MG Injection and BD PosiFlush (saline)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 152 participants
- Where
- 1 siteDenmark
- Study dates
- 7 Aug 2017to 5 Oct 2020
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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)
Show all 22Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Glucagon-like Peptide (GLP-1) Receptor Agonist Stimulation Reduce Alcohol Intake in Patients With Alcohol Dependence?
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.
Read the detailed description
Number of patients and target population:
144 patients with a diagnosis of alcohol dependence and 25 healthy participants (described later).
The patients included in the trial will be treated for 26 weeks with once-weekly subcutaneous injection of Bydureon® (exenatide) 2 mg or placebo. The medication will be provided as a supplement to a standard, psychosocial alcohol treatment program. There will be a long-term follow up 26 weeks after end of participation in the trial
Recruitment of the patients:
The patients will be recruited from the out-patient treatment clinics "Novavì ambulatorierne" in suburbs of Copenhagen. All patients will receive psychosocial alcohol treatment based on psycho educative elements, motivational interviewing and cognitive behavioural treatment. Skilled staff members administer the treatment.
The recruitment procedure starts when the patients contact Novavì ambulatorierne. The first contact is often without any appointment - i.e. as "drop-in". At this point the patients will be met by a healthcare provider at his/her local Novavì ambulatorie. The healthcare provider will be a nurse or a doctor. The patient will be treated in accordance to the Novavì guidelines, i.e. start of abstinence treatment and a plan will be agreed on. At this point, the health personal will also ask if the patient could be interested in our project. Information regarding the project will also be available on the web page of Novavì. If he/she is interested and the patient fits the inclusion criteria the patient will be handed written information about the trial, and an information meeting will be set up a few days later. The patient will be informed about his/her right to bring a friend or adviser.
Pre-treatment evaluation/screening:
Before screening, all patients will be provided with oral and written information about the trial, including the most common adverse events, and the procedures involved in the study. All patients will be fully in-formed, verbally and in writing, of their rights and responsibilities while participating in the trial. Screening examinations will only be performed after the patient has agreed to participate and has signed and dated the informed consent form.
Screening:
At screening examinations, the patient will be asked about his/her alcohol intake the previous 30 days. The information will be recorded via TLFB (Time Line Follow Back) method. The patient will be asked questions about his/her lifetime alcohol consumption, previous treatment and general information about psychosocial factors, i.e. education level, employment and marital status.
In addition, Alcohol Users Identification Test (AUDIT) score, the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar), The Drug User Identification Test (DUDIT) score, Major Depression Inventory (MDI) score (related to the SPECT results), Penn alcohol craving scale (PACS), smoking status (Fagerströms test), height, weight, waist circumference, blood pressure and pulse will be registered. In order to evaluate psychosocial status a general assessment including questionnaires regarding health (SF-36), Symptom checklist (SCL-92) and Screen for Cognitive Impairment in Psychiatry (SCIP) - test will be performed.The patients will also be asked questions regarding somatic symptoms, i.e. GI-symptoms, in order to obtain baseline information. In addition, other medications than Bydureon® will be registered.
Different safety blood samples and a urine test will be collected. A blood sample and a urine sample will be saved for an investigational biobank and a biobank for future research.
Weekly visits:
The patient will meet every week to get his/her weekly injection by the un-blinded nurse. The nurse will collect a weekly alcohol diary and hand them a new one, for the following week.
Examinations during and in the end of the trial:
At week 4, 12 and 20, parts of the baseline examinations - including blood samples - will be conducted. The alcohol diaries collected in relation to the weekly injection-visits will be used as template for the 30 day TLFB at the examinations, i.e. the examiner will fill out the TLFB based on the diaries and in close collaboration with the patient. At week 26, the final examination will take place repeating all the baseline examinations.
Long-term follow up 26 weeks after end of participation in the trial:
All participants completing the final week 26 examination, will be contacted after six months, and invited to a follow up meeting . TLFB, PACS, AUDIT and Fagerstrøms questionnaire will be repeated. A new questionnaire, which gives us a better characteristic of the patient's alcohol history, "Alco-life" will be registered. A single blood test, (PEth) will be collected.
Study of the possible neuro molecular and -anatomical underpinnings:
In addition to the clinical outcome parameters, the investigators will explore the neuro molecular and -anatomical underpinnings of potential therapeutic effects of Bydureon® in two subgroups of patients who are treated with either Bydureon® or placebo. In order to study this,two different brain scans will be performed: Single-photon emission computed tomography (SPECT)-scan (sixty) and functional Magnetic Resonance Imaging (fMRI)-scan (seventy-five patients) at baseline and after 26 weeks of treatment. The patients will be included continuously until the aimed number (i.e. sixty and seventy-five patients for each scan type, respectively) have completed base line scan. The patients will be asked to undergo both scan types (except from the last fifteen patients out of the seventy-five patients included for scans, who will only undergo fMRI scan) as the information from both scans will be paired during evaluation. When baseline scans are performed, the patients start the treatment they were randomized for at inclusion.
The SPECT-scan:
Studies have lately reported on a GLP-1-induced upregulation of the rat dopamine transporter activity in vitro. In the present study, the investigators want to investigate whereas GLP-1 receptor stimulation induces changes in the striatal dopamine transporter availability in humans. The investigators will conduct the SPECT brain scan with the dopamine transporter ligand 123I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([123I]-FP-CIT) (DaTSCAN, Amersham Health). The SPECT scans will be conducted at the Neurobiology Research Unit, Rigshospitalet.
The fMRI-scan:
The fMRI-scan measures brain blood flow, which reflects activity in different areas of the brain. We will test two different paradigms: 1) Alcohol cue sensitivity. Sixty alcohol-related and 45 neutral stimuli are presented using a block design. Following each block, the patients rate the intensity of their alcohol craving on a visual analogue scale ranging from 0 (no craving) to 100 (extremely extensive craving). 2) Spatial working memory. Spatial working memory is assessed using 2-back and 0-back variants of the N-back task for the active working memory and control conditions.
Study-schedule for the 25 healthy fMRI-participants:
To have comparable standard data in the fMRI alcohol related paradigm, 25 healthy participants with no record of alcohol dependence will be recruited. The participants will be matched with gender and age of the patients and have to fulfil the exclusion-criteria.
Day 1: The participants will have an interview about physical symptoms, diagnosis and current medication. They will be asked to fill out the Alcohol Users Identification Test (AUDIT), the Drug Users Identification Test (DUDIT), have a basic physical examination and a blood and a urine test done.
Day 2: They will start with the Screen for Cognitive Impairment in Psychiatry (SCIP) test, and afterwards have the fMRI scan done.
- Being tested
- Exenatide 2 MG Injection, BD PosiFlush (saline)
- Keywords
- Alcohol, Addiction, Glucagon Like Peptide-1, GLP-1
- Medical subject headings
- Alcoholism, Behavior, Addictive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Exenatide 2 MG InjectionDrug
Also called Bydureon Pen, 2 Mg, Extended Release
Subcutaneous injection once-weekly
BD PosiFlush (saline)Drug
Also called Saline
Subcutaneous injection once-weekly
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Drug: BD PosiFlush (saline) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks
Secondary outcomes (20)
Total alcohol consumption
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.
Measured: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks
Penn Alcohol Craving Scale (PACS) score
Score for measuring alcohol craving
Measured: Baseline and 26 weeks
Alcohol Use Disorders Identification Test (AUDIT) score
Screening for excessive drinking
Measured: Baseline and 26 weeks
Drug Use Disorders Identification Test (DUDIT) score
A parallel instrument to the AUDIT for identification of individuals with drug-related problems
Measured: Baseline and 26 weeks
Screen For Cognitive Impairment in Psychiatry (SCIP) test
The 20 minute test is a simple scale developed for screening cognitive deficits
Measured: Baseline, 4 weeks and 26 weeks
Plasma-gamma-glutamyltransferase (GGT)
Liver parameter
Measured: Baseline and 26 weeks
Plasma-alanine aminotransferase (ALAT)
Liver parameter
Measured: Baseline and 26 weeks
Plasma-phosphatidylethanol (PEth)
Biomarker for alcohol consumption
Measured: Baseline, 4, 12, 20 and 26 weeks
Blood-mean cell volume
Measure of the average volume of a red blood cell
Measured: Baseline and 26 weeks
Body weight
Body weight in kilograms
Measured: Baseline, 4, 12, 20 and 26 weeks
Blood pressure
Systolic and diastolic blood pressure
Measured: Baseline, 4, 12, 20 and 26 weeks
Pulse
Number of heartbeats pr. minute
Measured: Baseline, 4, 12, 20 and 26 weeks
Waist circumference
Widest abdominal circumference in centimeters
Measured: Baseline, 4, 12, 20 and 26 weeks
Plasma-glycemic control parameters
HbA1c, cholesterol, triglycerides, high-density lipoprotein (HDL), low-density lipoprotein (LDL).
Measured: Baseline and 26 weeks
Kidney function
e-GFR, urine albumine/creatinine-ratio.
Measured: Baseline and 26 weeks (eGFR also at week 12)
Short Form Health Survey (SF-36)
36-item, patient-reported survey of patient health
Measured: Baseline and 26 weeks
Plasma amylase
Safety (i.e. pancreatic function)
Measured: Baseline and 26 weeks
Symptom Checklist (SCL-92)
92-item, patient-reported survey of a broad range of psychological problems and symptoms of psychopathology.
Measured: Baseline and 26 weeks
Single-photon emission computed tomography (SPECT)
In this study we want to investigate whereas GLP-1 receptor stimulation induces changes in the striatal dopamine transporter availability in humans.
Measured: Baseline and 26 weeks
fMRI (functional magnetic resonance imaging)
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.
Measured: Baseline and 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jul 2017
- Study start7 Aug 2017
- Primary completion15 Mar 2020
- Study completion5 Oct 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol Dependence, in RemissionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blinded, randomized, placebo-controlled.
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 152 participants (actual)
Sponsor and investigators
- Lead sponsor
- Anders Fink-Jensen, MD, DMSci
- Sponsor type
- University, hospital or other
- Collaborators
- The Novavì outpatient clinics, Copenhagen, Copenhagen University Hospital, Rigshospitalet, University of Copenhagen
- Responsible party
- Sponsor-investigator, Anders Fink-Jensen, MD, DMSci, Psychiatric Centre Rigshospitalet
- Investigators
- Signe W. Düring, MD, Principal investigator, The Novavi outpatient clinics, Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03232112
- Sponsor's protocol ID
- EXALT study
- Acronym
- EXALT
- Status last verified
- Jun 2021
- First submitted
- 20 Jul 2017
- Last updated
- 4 Jun 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 36066977
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Glucagon-like Peptide (GLP-1) Receptor Agonist Stimulation Reduce Alcohol Intake in Patients With Alcohol Dependence?
- ClinicalTrials.gov ID
- NCT03232112
- Acronym / sponsor ID
- EXALT / EXALT study
- Keywords
- Alcohol, Addiction, Glucagon Like Peptide-1, GLP-1
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 152 participants (actual)
- Lead sponsor
- Anders Fink-Jensen, MD, DMSciUniversity, hospital or other
- Collaborators
- The Novavì outpatient clinics, Copenhagen, Copenhagen University Hospital, Rigshospitalet, University of Copenhagen
- Study start
- 7 Aug 2017 (actual)
- Primary completion
- 15 Mar 2020 (actual)
- Study completion
- 5 Oct 2020 (actual)
- First posted
- 27 Jul 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Number of patients and target population:
144 patients with a diagnosis of alcohol dependence and 25 healthy participants (described later).
The patients included in the trial will be treated for 26 weeks with once-weekly subcutaneous injection of Bydureon® (exenatide) 2 mg or placebo. The medication will be provided as a supplement to a standard, psychosocial alcohol treatment program. There will be a long-term follow up 26 weeks after end of participation in the trial
Recruitment of the patients:
The patients will be recruited from the out-patient treatment clinics "Novavì ambulatorierne" in suburbs of Copenhagen. All patients will receive psychosocial alcohol treatment based on psycho educative elements, motivational interviewing and cognitive behavioural treatment. Skilled staff members administer the treatment.
The recruitment procedure starts when the patients contact Novavì ambulatorierne. The first contact is often without any appointment - i.e. as "drop-in". At this point the patients will be met by a healthcare provider at his/her local Novavì ambulatorie. The healthcare provider will be a nurse or a doctor. The patient will be treated in accordance to the Novavì guidelines, i.e. start of abstinence treatment and a plan will be agreed on. At this point, the health personal will also ask if the patient could be interested in our project. Information regarding the project will also be available on the web page of Novavì. If he/she is interested and the patient fits the inclusion criteria the patient will be handed written information about the trial, and an information meeting will be set up a few days later. The patient will be informed about his/her right to bring a friend or adviser.
Pre-treatment evaluation/screening:
Before screening, all patients will be provided with oral and written information about the trial, including the most common adverse events, and the procedures involved in the study. All patients will be fully in-formed, verbally and in writing, of their rights and responsibilities while participating in the trial. Screening examinations will only be performed after the patient has agreed to participate and has signed and dated the informed consent form.
Screening:
At screening examinations, the patient will be asked about his/her alcohol intake the previous 30 days. The information will be recorded via TLFB (Time Line Follow Back) method. The patient will be asked questions about his/her lifetime alcohol consumption, previous treatment and general information about psychosocial factors, i.e. education level, employment and marital status.
In addition, Alcohol Users Identification Test (AUDIT) score, the Clinical Institute Withdrawal Assessment of Alcohol Scale Revised (CIWA-Ar), The Drug User Identification Test (DUDIT) score, Major Depression Inventory (MDI) score (related to the SPECT results), Penn alcohol craving scale (PACS), smoking status (Fagerströms test), height, weight, waist circumference, blood pressure and pulse will be registered. In order to evaluate psychosocial status a general assessment including questionnaires regarding health (SF-36), Symptom checklist (SCL-92) and Screen for Cognitive Impairment in Psychiatry (SCIP) - test will be performed.The patients will also be asked questions regarding somatic symptoms, i.e. GI-symptoms, in order to obtain baseline information. In addition, other medications than Bydureon® will be registered.
Different safety blood samples and a urine test will be collected. A blood sample and a urine sample will be saved for an investigational biobank and a biobank for future research.
Weekly visits:
The patient will meet every week to get his/her weekly injection by the un-blinded nurse. The nurse will collect a weekly alcohol diary and hand them a new one, for the following week.
Examinations during and in the end of the trial:
At week 4, 12 and 20, parts of the baseline examinations - including blood samples - will be conducted. The alcohol diaries collected in relation to the weekly injection-visits will be used as template for the 30 day TLFB at the examinations, i.e. the examiner will fill out the TLFB based on the diaries and in close collaboration with the patient. At week 26, the final examination will take place repeating all the baseline examinations.
Long-term follow up 26 weeks after end of participation in the trial:
All participants completing the final week 26 examination, will be contacted after six months, and invited to a follow up meeting . TLFB, PACS, AUDIT and Fagerstrøms questionnaire will be repeated. A new questionnaire, which gives us a better characteristic of the patient's alcohol history, "Alco-life" will be registered. A single blood test, (PEth) will be collected.
Study of the possible neuro molecular and -anatomical underpinnings:
In addition to the clinical outcome parameters, the investigators will explore the neuro molecular and -anatomical underpinnings of potential therapeutic effects of Bydureon® in two subgroups of patients who are treated with either Bydureon® or placebo. In order to study this,two different brain scans will be performed: Single-photon emission computed tomography (SPECT)-scan (sixty) and functional Magnetic Resonance Imaging (fMRI)-scan (seventy-five patients) at baseline and after 26 weeks of treatment. The patients will be included continuously until the aimed number (i.e. sixty and seventy-five patients for each scan type, respectively) have completed base line scan. The patients will be asked to undergo both scan types (except from the last fifteen patients out of the seventy-five patients included for scans, who will only undergo fMRI scan) as the information from both scans will be paired during evaluation. When baseline scans are performed, the patients start the treatment they were randomized for at inclusion.
The SPECT-scan:
Studies have lately reported on a GLP-1-induced upregulation of the rat dopamine transporter activity in vitro. In the present study, the investigators want to investigate whereas GLP-1 receptor stimulation induces changes in the striatal dopamine transporter availability in humans. The investigators will conduct the SPECT brain scan with the dopamine transporter ligand 123I-2-b-carbomethoxy-3b-(4-iodophenyl)-N-(3-fluoropropyl) nortropane ([123I]-FP-CIT) (DaTSCAN, Amersham Health). The SPECT scans will be conducted at the Neurobiology Research Unit, Rigshospitalet.
The fMRI-scan:
The fMRI-scan measures brain blood flow, which reflects activity in different areas of the brain. We will test two different paradigms: 1) Alcohol cue sensitivity. Sixty alcohol-related and 45 neutral stimuli are presented using a block design. Following each block, the patients rate the intensity of their alcohol craving on a visual analogue scale ranging from 0 (no craving) to 100 (extremely extensive craving). 2) Spatial working memory. Spatial working memory is assessed using 2-back and 0-back variants of the N-back task for the active working memory and control conditions.
Study-schedule for the 25 healthy fMRI-participants:
To have comparable standard data in the fMRI alcohol related paradigm, 25 healthy participants with no record of alcohol dependence will be recruited. The participants will be matched with gender and age of the patients and have to fulfil the exclusion-criteria.
Day 1: The participants will have an interview about physical symptoms, diagnosis and current medication. They will be asked to fill out the Alcohol Users Identification Test (AUDIT), the Drug Users Identification Test (DUDIT), have a basic physical examination and a blood and a urine test done.
Day 2: They will start with the Screen for Cognitive Impairment in Psychiatry (SCIP) test, and afterwards have the fMRI scan done.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Double-blinded, randomized, placebo-controlled.
| Arm | Type | Receives |
|---|---|---|
| Exenatide 2 MG Injection | Active comparator | Drug: Exenatide 2 MG InjectionBydureon® (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. |
| BD PosiFlush (saline) | Placebo comparator | Drug: 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. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (22 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Exenatide 2 MG InjectionAlso: Bydureon Pen, 2 Mg, Extended ReleaseSubcutaneous injection once-weekly | Drug | Exenatide 2 MG Injection |
| BD PosiFlush (saline)Also: SalineSubcutaneous injection once-weekly | Drug | BD PosiFlush (saline) |
Primary outcome
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.
20 secondary outcomes
Total alcohol consumption
Time frame: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks
Penn Alcohol Craving Scale (PACS) score
Time frame: Baseline and 26 weeks
Alcohol Use Disorders Identification Test (AUDIT) score
Time frame: Baseline and 26 weeks
Drug Use Disorders Identification Test (DUDIT) score
Time frame: Baseline and 26 weeks
Screen For Cognitive Impairment in Psychiatry (SCIP) test
Time frame: Baseline, 4 weeks and 26 weeks
Plasma-gamma-glutamyltransferase (GGT)
Time frame: Baseline and 26 weeks
Plasma-alanine aminotransferase (ALAT)
Time frame: Baseline and 26 weeks
Plasma-phosphatidylethanol (PEth)
Time frame: Baseline, 4, 12, 20 and 26 weeks
Blood-mean cell volume
Time frame: Baseline and 26 weeks
Body weight
Time frame: Baseline, 4, 12, 20 and 26 weeks
Blood pressure
Time frame: Baseline, 4, 12, 20 and 26 weeks
Pulse
Time frame: Baseline, 4, 12, 20 and 26 weeks
Waist circumference
Time frame: Baseline, 4, 12, 20 and 26 weeks
Plasma-glycemic control parameters
Time frame: Baseline and 26 weeks
Kidney function
Time frame: Baseline and 26 weeks (eGFR also at week 12)
Short Form Health Survey (SF-36)
Time frame: Baseline and 26 weeks
Plasma amylase
Time frame: Baseline and 26 weeks
Symptom Checklist (SCL-92)
Time frame: Baseline and 26 weeks
Single-photon emission computed tomography (SPECT)
Time frame: Baseline and 26 weeks
fMRI (functional magnetic resonance imaging)
Time frame: Baseline and 26 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2021.
- Derived from this study: PubMed 36066977Klausen 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Signe W. Düring, MD principal investigator
The Novavi outpatient clinics, Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Exenatide 2 MG Injection and BD PosiFlush (saline) in people with Alcohol Dependence, in Remission and Addiction, Alcohol, run by Anders Fink-Jensen, MD, DMSci at 1 site in Denmark.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Heavy drinking days (time frame: 30 days prior to baseline and 30 days prior to final follow up at 26 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03232112, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2021.