Investigation of the Efficacy of Acamprosate and Calcium in Comparison to Placebo as Validation of a Behavioural Test for Alcohol Dependence (TEMACA)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Enrollment
- 82
- Locations
- 1
- Primary Endpoint
- Difference between cumulative CAT trials for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day
Study Overview
Brief Summary
Validation of a Test System to develop new medications for alcoholism (TEMA)
The 'TEMA', a progressive-work alcohol self-administration paradigm, can be validated by reproducing the effect of Acamprosate and prove the effect of Calcium to reduce motivation to work for alcohol after 14 - 19 days of treatment during a period of 15 - 20 days of alcohol abstinence in a randomized, double-blind, placebo-controlled three-arm parallel-group design.
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.
84 at least high risky drinkers (WHO) with at least mild alcohol use disorder perform two alcohol self-administration experiments, one before and one after 14-19 days of randomized double-blinded treatment with Acamprosate, Calcium Carbonate or Placebo.
Each alcohol request requires prior work in a constant attention task according to a progressive schedule to earn the next alcohol infusion.
Secondary objectives refer to investigations, whether
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Basic Science
- Masking
- Triple (Participant, Care Provider, Investigator)
Eligibility Criteria
- Ages
- 25 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •male and female volunteers aged 25 to 55 years, who meet or met the diagnostic criteria of an at least mild alcohol use disorder (DSM-5), but do not want to cease alcohol consumption
- •willingness to stop alcohol and drug consumption for 15-20 days for the purpose of study participation
- •at least high risky alcohol drinkers (WHO) in the Timeline Follow-back Interview over the last 45 day with an average amount of alcohol of 60 g/day (men) or 40 g/day (women) with at least 4 drinking days per week
- •informed consent
- •ability to swallow a placebo capsule
- •not more than 6 consecutive alcohol abstinent days between screening and visit 2
Exclusion Criteria
- •Current Substance dependence (illegal drugs) ICD-10 or DSM-IV
- •Intention to stop alcohol consumption immediately and permanently
- •Current or previous disease that could cause a clinically relevant hazard (e.g. pancreatitis, cirrhosis)
- •kidney stone disease
- •Current Treatment with psychotropic drugs or current psychiatric disorder in need of treatment
- •alcohol withdrawal symptoms (at Screening, visit 1 or visit 2) with CIWA-Ar-Score > 6 points or arterial blood pressure >160 mm Hg or diastolic blood pressure > 100 mm Hg or heart rate >105 bpm (when breath alcohol concentration 0 mg%)
- •history of epileptic seizure or delirium
- •routine laboratory parameters, indicating relevant liver-, pancreas- or kidney injury, an acute infection, anemia or lack of vitamins (ASAT, ALAT, lipase > threefold of the standard at screening, Quick's value < 70%, creatinine > 120 µmol/l, eGFR < 30 mol/min/1.73 m², leucocytes > 13000/µl, haemoglobin < 7.5 mmol/l (men) or 6.5 mmol/l (women), MCV > 105 fl, calcium level at screening > 2.7 mmol/l
- •body weight > 120 kg (Screening)
- •Breath alcohol concentration at screening or visit 1 or visit 2 two times > 0 mg% or drug screening two times positive for opiate, cannabis, cocaine, amphetamine, benzodiazepine
- •history of hypersensitivity to alcohol or one of the used medicinal products, of their ingredients or medicinal products with similar chemical structures
- •history of inefficient treatment with Acamprosate
- •participation in another clinical trial within the last 4 weeks before inclusion
- •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)
- •participant is not expected to comply with the protocol (for example lacking compliance)
- •less than 200 cumulative work trials for alcohol (in constant attention task) on 1st alcohol self-administration day
- •specific contraindications for Acamprosate or Calcium Carbonate (according prescribing information)
- •hypercalcemia, e.g. due to hyperparathyroidism, overdosage vitamin D, paraneoplastic
- •renal insufficiency (eGFR < 30ml/min/1.73m²), creatinine >120 µmol/l
- •intake of Vitamin D compounds or cardioactive glycosides
Arms & Interventions
Acamprosate
1 capsule with Acamprosate calcium
- oral use
- 3 times / day (morning, noon, evening)
- 666 mg per capsule
- 14 - 19 days
Intervention: Acamprosate Calcium (Drug)
Acamprosate
1 capsule with Acamprosate calcium
- oral use
- 3 times / day (morning, noon, evening)
- 666 mg per capsule
- 14 - 19 days
Intervention: Placebo lead in (Drug)
Calcium Carbonate
1 capsule with Calcium Carbonate
- oral use
- 3 times / day (morning, noon, evening)
- 1500 mg Calcium Carbonate (= 600 mg Calcium 2+)
- 14 - 19 days
Intervention: Calcium Carbonate (Drug)
Calcium Carbonate
1 capsule with Calcium Carbonate
- oral use
- 3 times / day (morning, noon, evening)
- 1500 mg Calcium Carbonate (= 600 mg Calcium 2+)
- 14 - 19 days
Intervention: Placebo lead in (Drug)
Placebo
1 capsule placebo,
- oral use
- 3 times / day (morning, noon, evening)
- 14 - 19 days
Intervention: Placebo (Drug)
Placebo
1 capsule placebo,
- oral use
- 3 times / day (morning, noon, evening)
- 14 - 19 days
Intervention: Placebo lead in (Drug)
Outcomes
Primary Outcomes
Difference between cumulative CAT trials for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day
Time Frame: 18 to 31 days between 1st and 2nd measurement
Each alcohol request requires prior work according to a progressive schedule (i.e., runs of the constant attention task) to earn the next alcohol infusion. Primary outcome measure is the difference in the cumulative number of work sets for alcohol in the "constant attention task" (CAT) between first alcohol self-administration day (baseline, without medication, visit 2) and the second alcohol self-administration day (after 14-19 days medication, visit 5). Comparison between: 1. Acamprosate and Placebo and 2. Calcium Carbonate and Placebo
Secondary Outcomes
- Difference between "break points" for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day(18 to 31 day between 1st and 2nd measurement)
- Difference between cumulative CAT trials for sodium chloride on 1st alcohol self-administration (ASA) day and 2nd ASA day.(18 to 31 days between 1st and 2nd measurement)
- Difference between max. achieved blood alcohol concentrations (BAC) on 1st alcohol self-administration (ASA) day and 2nd ASA day(18 to 31 day between 1st and 2nd measurement)
- Differences in 1st and 2nd half of self-administration periods between cumulative CAT trials for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day of 1st and 2nd half of self-administration periods.(18 to 31 days between 1st and 2nd measurement)
- Differences in 1st and 2nd half of self-administration periods between "break points" for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day.(18 to 31 days between 1st and 2nd measurement)
- Differences in 1st and 2nd half of self-administration periods between max. achieved blood alcohol concentrations (BAC) for alcohol on 1st alcohol self-administration (ASA) day and 2nd ASA day.(18 to 31 days between 1st and 2nd measurement)
- Differences in 1st and 2nd half of self-administration periods between cumulative CAT trials for sodium chloride on 1st alcohol self-administration (ASA) day and 2nd ASA day.(18 to 31 days between 1st and 2nd measurement)
- Differences between subjective alcohol effects on 1st ASA day and 2nd ASA day(18 to 31 days between 1st and 2nd measurement)
- Calcium parameters on 1st ASA and 2nd ASA day(18 to 31 day between 1st and 2nd measurement)
- Alcohol craving (OCDS) "Obsessive Compulsive Drinking Scale" (OCDS)(18 to 31 days between 1st and 2nd measurement)
- Violation of imposed alcohol abstinence(15-20 days (abstinence period))
- Readiness to change(39 - 90 days between screening and visit 6, 6-8 weeks between visit 6 and follow-up)
- Drinking habits(39 - 90 days between screening and visit 6, 32 - 55 days between visit 1 and visit 6)
- utilization of addiction care services(39 - 90 days between screening and visit 6, 32 - 55 days between visit 1 and visit 6)
- Acid sphingomyelinase (ASM) activities(screening, 18 to 31 day between 1st and 2nd measurement, 2.5 hours from begin to end of ASA)
- Acamprosate blood level(one-time measurement after 14 - 19 days of medication intake (at visit 5))