Clinical trial NCT02652585: Validation of a Test System for Development of Medications for Alcoholism
Official title: Validation of a Test System for Development of Medications for Alcoholism
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Alcoholism
Keywords: Alcoholism
alcohol self-administration
Lead sponsor: Technische Universität Dresden
Sponsor class: OTHER
First posted: 2016-01-12
Enrollment: 46
Sex: ALL
Minimum age (years): 25
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: Using theTEMA (test system for development of medications for alcoholism) it can be shown, that naltrexone administration reduces the willingness to perform work for alcohol infusion in a laboratory experiment.

Detailed description: Objective of this study is to show that a laboratory alcohol self-administration method can predict the therapeutic potential of new compounds to reduce relapse in alcohol-dependent patients.

The 'TEMA" translates several animal behavioral paradigms of alcohol self-administration into corresponding human experiments.

We will investigate the opiate antagonist Naltrexone, whose anti-relapse effect is well documented, as a reference drug for validation.

Main objective:

With TEMA (test system for development of medications for alcoholism ) it can be shown, that naltrexone administration reduces the willingness to perform work for alcohol infusion in a laboratory experiment.

Secondary objectives:

* administration of naltrexone in comparison to placebo leads to a reduction of alcohol craving and real-life drinking
* administration of naltrexone in comparison to placebo leads to reduction of the CDT-Level
* administration of naltrexone in comparison to placebo leads to a change in perception of subjective alcohol effects
* the effectiveness of naltrexone can be predicted by the A118G polymorphism of the OPRM1
* administration of naltrexone changes the baseline and alcohol-induced ability of motor inhibition
* administration of naltrexone changes the baseline and alcohol-induced regional cerebral perfusion
* administration of naltrexone changes the baseline and alcohol-induced cerebral resting state activity
* changes of alcohol effects to the brain activity induced by naltrexone in comparison to placebo correlate with effects of naltrexone on the willingness to work for alcohol self-administration

Eligibility criteria: Inclusion Criteria:

* male and female volunteers aged 25 to 55 years
* at least weekly alcohol consumption at a medium risk level according to WHO in the Timeline Follow-back Interview over the last 45 day with an average amount of alcohol of 41 g/day (men) or 31 g/day (women)
* at least 6 days with an alcohol consumption of \>100 g/day (men) or 75 g/day (women) and at least 4 non consecutive alcohol abstinent days in the last 45 days
* at least 1 drinking day in each full week between screening and visit 1 and not more than 6 abstinent days in the week before visit 1
* no demand of treatment of the risky alcohol consumption
* written consent after Information

Exclusion Criteria:

* a history of hypersensitivity against alcohol or one of the used medicinal products, of their ingredients or medicinal products with similar chemical structures
* participation in another clinical trial within the last 4 weeks before inclusion
* addiction or other disorders, which will not allow the subject to assess the character and importance or possible consequences of the clinical trial
* pregnant or breastfeeding women
* women capable of bearing children, except women who fulfil following criteria:- post-menopausal (12 months natural amenorrhoea or 6 month amenorrhoea and Serum FSH \>40 ml U/ml) - post operative (6 weeks after ovariectomy on both sides with or without hysterectomy) - regular and correct use of a contraceptive method with an error Quote of \< 1 % per year (for example implants, depot injections, oral contraceptive, IUP). It has to be recognized that a combined oral contraception - in contrast to pure progesterone compounds - have a failure rate of \< 1 %. Hormone IUDs with a Pearl Index of 1 % are safer than copper IUDs. - sexual abstinence - vasectomy of the Partner
* evidence that the participant is not expected to comply with the protocol (for example lacking compliance)
* current or previous alcohol or substance dependence according to DSM-IV (exception: tobacco dependence)
* current or previous treatment because of alcohol, for example in an addiction advisory cen-tre, self-help group, detoxification treatment
* current or previous diseases, where an alcohol infusion can cause a clinically relevant hazard (e. g. pancreatitis, liver cirrhosis)
* current or planned intake of opiate analgesics
* current psychiatric treatment or intake of psychiatric drug or suffering from of a psychiatric disease requiring treatment
* a history of suicide attempt
* CIWA-Score \>5 at Screening (alcohol withdrawal scale)
* a history of symptoms of alcohol withdrawal, epileptic seizures or delirium
* routine laboratory Parameters, indicating relevant liver-, pancreas- or kidney injury, an acute infection, anaemia or lack of vitamins (ASAT, ALAT \> twofold of the standard at screening, gamma-GT, lipase \>threefold of the standard, CRP \< 15 mg/l, creatin indicating a moderate renal insufficiency ( eGFR \<60 ml/min), leucocytes \> 12000/µl, haemoglobin \< 7,5 mmol/l (men) or 6,5 mmol/l (women), MCV \> 100 fl)
* Body weight \> 130 kg
* drug screening in urine: once positive at screening for opiate, cannabis, cocaine, amphetamines, benzodiazepines or positive once at visit 1 for opiates or positive twice at visit 1 for cannabis, cocaine, amphetamines, benzodiazepines
* breath alcohol concentration at screening once \> 0,00 g/kg or twice \>0,00 g/kg at visit 1
* unsuitable for fMRT (e. g. cardiac pacemaker, claustrophobia)
* specific contraindications against naltrexone: o acute hepatitis o severe or acute liver disease o severe kidney disease o rare hereditary galactose intolerance, Lapp-lactase-deficiency or Glucose-galactose-malabsorption

Primary outcomes:
measure: Difference CAT Trials alcohol
timeFrame: one year
Secondary outcomes:
measure: Difference CAT Trials sodium chloride solution
timeFrame: one year
measure: break Point alcohol
timeFrame: one year
measure: max. BAC
timeFrame: one year
measure: Drinking habits
timeFrame: one year
measure: CDT - level
timeFrame: one year
measure: alcohol craving
timeFrame: one year
measure: subjective alcohol effects
timeFrame: one year
measure: motor impulse control
timeFrame: one year
measure: cerebral blood flow (CBF)
timeFrame: one year
measure: Cerebral resting state activity
timeFrame: one year
measure: adverse events
timeFrame: one year
measure: ALAT
timeFrame: one year
measure: ASAT
timeFrame: one year
measure: Gamma-GT
timeFrame: one year
measure: standard blood cell count
timeFrame: one year
measure: creatinine
timeFrame: one year
measure: lipase
timeFrame: one year
measure: CRP
timeFrame: one year
Other outcomes:
Locations:
city: Dresden
country: Germany
facility: Klinik und Poliklinik für Psychiatrie und Psychotherapie
Study officials:
affiliation: Klinik und Poliklinik für Psychiatrie und Psychotherapie Unversitätsklinikum Carl Gustav Carus Dresden
name: Ulrich S Zimmermann, MD
role: STUDY_DIRECTOR
References: