Investigation of the efficacy of acamprosate and calcium in comparison to placebo as validation of a behavioural test for alcohol dependence (TEMACA) - TEMACA

INTERVENTION: Product Name: Acamprosat‐Calcium Pharmaceutical Form: Capsule, hard INN or Proposed INN: Acamprosat‐Calcium CAS Number: 77337‐73‐6 Current Sponsor code: Acamprosat‐Calcium Other descriptive name: 3‐Acetamido‐1‐propansulfonsäure Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 666‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Gastroenteral use Trade Name: Calciumcarbonat Product Name: Calciumcarbonat Pharmaceutical Form: Capsule, hard INN or Proposed INN: Calciumcarbonat Current Sponsor code: Calcium‐dura Other descriptive name: CALCIUM CARBONATE Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 1500‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Gastroenteral use Trade Name: Alkohol‐Konzentrat 95% Braun Pharmaceutical Form: Concentrate for solution for infusion INN or Proposed INN: Alkohol‐Konzentrat 95% CAS Number: 64‐17‐5 Other descriptive name: ETHANOL Concentration unit: % (V/V) percent volume/volume Concentration type: equal Concentration number: 95‐ CONDITION: persons with disturbance in alcohol use according DSM5 which do not want to change their alcohol consumption Therapeutic area: Psychiatry and Psychology [F] ‐ Behaviours [F01] PRIMARY OUTCOME: ; Main Objective: Validation of the behavior test "TEMA":; Can the TEMA demonstrate that the administration of acamprosate or ionised calcium (Ca2+ = Calciumcarbonat) reduces the willingness to work after a period of abstinence from alcohol of at least 15 (to 20) days in order to be able to drink alcohol?; ; Primary end point(s): The difference in the cumulative number of alcohol passes in the constant attention task between the first (V2) and second (V5) self‐administration experiments compared between the groups treated with acamprosate vs. placebo or calcium vs. placebo.; ; Secondary Objective: 1. Does the administration of acamprosate or calcium in comparison to placebo lead to a changed subjective perception of alcohol effects?; 2. Can the efficacy of Acamprosat or Ca2+ be predicted?; 3. Can the administration of Acamprosat or Ca2+ reduce the alcohol demand in everyday life?; 4. Are there differences between treatment groups in the frequency of alcohol consumption during the imposed abstinence period and how does this affect alcohol work after the imposed abstinence period?; 5. Does participation in the study encourage motivation to change drinking habits or does it change drinking habits or the use of addiction services?; 6. Is the activity of secreted sphingomyelinase suitable as a biomarker for alcohol consumption and prediction of drug action?; 7. Do safety problems arise in the use of the investigational medicinal products?; ; Timepoint(s) of evaluation of this end point: Values before the start of abstinence compared to values at the end of abstinence. Abstinence is 14 to 19 days.; Visite 2 = Visite 1 (screening + 7‐35 days) + 7‐10 days compared with; Visit 5 = Visit 4 (first day of medication) +13‐18 days; SECONDARY OUTCOME: ; Secondary end point(s): (A) Endpoints related to efficacy:; 1. other parameters of alcohol self‐administration; a.Difference between first and second self‐administration experiment in the break points in the progressive work scheme for the work; for alcohol; b.The difference of the maximum blood alcohol concentration (BAC) achieved between the first and second self‐administration experiments; c. The difference between the first and second self‐administration experiments in the cumulative number of working passes for saline solution; in the constant attention task.; d.Investigation of the primary and the above‐mentioned secondary parameters of alcohol self‐administration with separate consideration only of the; first or second half of the experiment; 2. alcohol‐induced change in values for subjective alcohol effects between first and second self‐administration experiment, recorded by; visual analogue scales ("quizzers") before, during and after the experiment in the 3 treatment groups; 3. baseline values and changes in calcium supply parameters between V2 and V5 (blood levels of total calcium, phosphate,; magnesium, albumin, parat‐hormone, 25‐hydroxy‐vitamin D) in the three treatment groups in relation to the primary target quantity.; 4. change of the alcohol demand in everyday life (by means of OCDS scores), measured in each case before both self‐administration experiments in the 3; treatment groups; 5. violations of imposed abstinence as a proportion (%) of days with alcohol consumption (as determined by Timeline Follow‐Back Interview (TLFB)) in; the three treatment groups and their influence on the primary target size; 6. stage of change motivation regarding drinking habits (readiness to change questionnaire) for screening, visit 6 and telephone; follow‐up; 7. drinking behaviour (using TLFB) for the period from 45 days prior to screening to one day prior to follow‐up telephone examination; 8. any reported use of the addiction assistance system, collected for screening and after the end of the study interventions; (Follow‐up examination V6 and telephone follow‐up examination); 9. initial values as well as change in activity of secreted acid sphingomyelinase (to screening and to both; self‐administration experiments, V2 and V5) in serum with respect to drinking behaviour, primary and secondary targets of the; self‐administration of alcohol and the effects of the medicaments thereon; 10. acamprosate levels with respect to primary and secondary targets of alcohol self‐administration in the acamprosate group; ; (B) Endpoints related to safety during and after the treatment period:; 1. medical questioning with regard to adverse events that occurred during visits V1 to V6; 2. CIWA‐Ar score, blood pressure and pulse values for screening and visits 1 to 6; ; Timepoint(s) of evaluation of this end point: 1. values before the start of abstinence compared with values at the end of abstinence. Abstinence is 14 to 19 days.; 2nd screening and 7 to 14 days as well as 6 to 8 weeks after abstinence.; 3. screening, before and after abstinence; INCLUSION CRITERIA: 1. Male and female volunteers aged 25 to 55 years who are currently or have a history of fulfilling the diagnostic criteria of an have at least a mildly pronounced alcohol abuse disorder in accordance with DSM‐5, but do not consume alcohol immediately and permanently to set the time. 2. Be willing to abstain continuously and completely from alcohol, sedatives and illicit drugs for 15‐20 days for the purpose of study participation. 3. According to WHO, high‐risk alcohol consumption with average drinking quantities for men: >60 g/day, for women >40 g/day in the timeline Follow‐back interview over the last 45 days before the screening examination, spread over an average of at least 4 drinking days per week. 4. Written consent of the participating person after clarification has been given . 5. Success