MAGnesium Adjunction in Alcohol Withdrawal Syndrome: a Multicenter Assessment (MAGMA)
Condition: Alcohol Withdrawal Syndrome
MeSH terms: Syndrome; Substance Withdrawal Syndrome
Study type: Interventional
Phase: Phase 3

Summary: 
      This study examine the efficacy of oral magnesium supplementation as an adjuvant therapy for
      decreasing intensity of alcohol withdrawal symptoms among inpatients requiring
      pharmacological treatment of their AWS. This double blind randomized multicenter clinical
      trial planned to treat half of participants as usal plus placebo and the other half as usual
      plus magnesium.
    

Detailed description: 
      Alcohol withdrawal syndrome (AWS) is a frequent and potentially fatal outcome. It is crucial
      to treat AWS in order to reduce symptoms severity, to prevent severe complications and to
      increase patient motivation to maintain long-term alcohol abstinence. Clarify the relevance
      of oral magnesium supplementation as a routine adjuvant therapy of AWS can give rise to a
      major evolution of guidelines regarding management of alcohol use disorder and make AWS more
      comfortable for hundred thousand patients.

      Magnesium acts as a competitor of glutamate on NMDA receptor binding site, limiting glutamate
      toxicity leading to AWS. Previous findings suggested a correlation between AWS intensity and
      hypomagnesaemia degree, and an increased risk of severe AWS (i.e. delirium tremens and
      seizure) when there is deep depletion. In addition to magnesium role as a glutamatergic
      modulator via an NMDA-receptor antagonism activity, magnesium may also modulate GABAergic
      neurotransmission and affect numerous transduction pathways, including proteinkinase C,
      possibly influencing the access of corticosteroids to the brain.

      Moreover, magnesium has been found to be a cofactor required for thiamine-dependent enzymes
      whereas thiamine supplementation is crucial to prevent from Wernicke's encephalopathy in the
      treatment of AWS. Finally, magnesium supplementation could help to reduce benzodiazepines
      use.

      The primary endpoint is the between-group absolute difference of the revised clinical
      institute withdrawal assessment for alcohol scale (CIWA-Ar) score change from baseline, 3
      days after randomization.

      The secondary endpoints are:

      a Total benzodiazepine consumption compared between experimental and control groups
      throughout the duration of the study (i.e. 15 days); b Time required to obtain a total score
      of 0 at the CIWA-Ar compared between experimental and control groups; c Rate of patients
      experiencing seizures and delirium tremens during the study compared between intervention and
      control groups; d Stratify results of the Primary endpoint following score at the Charlson
      Comorbidity Index; e Stratify results of the Primary endpoint by age; f Number of
      participants who left the hospital against medical advice during the study compared between
      experimental and control groups; g Number of participants who made an appointment in an
      addiction unit during the study (i.e. before the last follow-up point, 15 days after
      baseline), compared between experimental and control groups after stratification following
      AUD duration and number of previous addiction healthcare; h Patient Satisfaction
      Questionnaire-18 (PSQ-18) scores at the last follow-up point (i.e. days after baseline)
      compared between experimental and control groups; i Total plasmatic or serum magnesium
      concentration changes between baseline, 3 days after baseline, and 7 days after baseline; j
      Rate of all adverse events occurred during the study incidence compared between experimental
      and control groups;

      Practical procedure:

      Patients recruited are inpatients, hospitalized whatever the main reason for hospitalization
      (i.e. alcohol withdrawal syndrome or other reason). Inclusion visit starts with signature of
      informed consent, then confirms the eligibility and finally, ends with randomization and
      administration of the first dose of treatment. Patients are followed 15 days after baseline.
      Total plasmatic or serum magnesium concentration is dosed at baseline, 3 days and 7 days. In
      addition to CIWA-Ar and AUDIT, the following assessments are performed at baseline: Charlson
      comorbidity index, DIGS, SCL-90, MINI. We will use tablets of 465.4 mg of magnesium lactate
      dehydrate (Magnespasmyl©), which corresponds to 47.4mg of magnesium (i.e. 1.9mmol of
      magnesium per tablet). These tablets will be prescribed as follows: 3 tablets three times per
      day. In case of diarrhea, nearly half-dosage will be used until the end of the follow-up
      (i.e. 189.6mg per day, 3 times a day as follows: 1 tablet, 2 tablets, 1 tablet). Patients
      will be informed that treatment is to be taken during meals and to avoid sodas during the
      study.
    

Intervention name(s): Magnesium; Placebo Oral Tablet
Intervention type(s): Drug; Drug
Intervention description(s): Usual care (i.e. without any restriction of drug therapy) plus oral tablet magnesium supplementation: 426.6mg of magnesium per day three times daily (i.e. 142.2 mg for each shot) throughout the study (i.e. fifteen days). In case of diarrhea, nearly half-dosage will be used (i.e. 189.6mg).; Usual care (i.e. without any restriction of drug therapy) plus oral placebo, totally similar to the verum, three times daily throughout the study (i.e. fifteen days). In case of diarrhea, nearly half-dosage will be used.
Other intervention name(s): Placebo
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Alcoholism; Delirium; Magnesium Deficiency