Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03232112 |
| Other study ID # |
EXALT study |
| Secondary ID |
|
| Status |
Completed |
| Phase |
Phase 2
|
| First received |
|
| Last updated |
|
| Start date |
August 7, 2017 |
| Est. completion date |
October 5, 2020 |
Study information
| Verified date |
June 2021 |
| Source |
Psychiatric Centre Rigshospitalet |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical 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.
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.
