Validation of a Test System for Development of Medications for Alcoholism (TEMANX)

Technische Universität Dresden

Status and phase

Completed

Phase 3

Conditions

Alcoholism

Treatments

Drug: Placebo

Drug: Naltrexone

Study type

Interventional

Funder types

Other

Identifiers

NCT02652585

TUD-TEMANX-065

Details and patient eligibility

About

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.

Full 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

Enrollment

46 patients

Sex

All

Ages

25 to 55 years old

Volunteers

Accepts Healthy Volunteers

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