Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03033823 |
| Other study ID # |
P150939 |
| Secondary ID |
2016-002072-26PH |
| Status |
Completed |
| Phase |
Phase 3
|
| First received |
|
| Last updated |
|
| Start date |
November 16, 2017 |
| Est. completion date |
October 23, 2020 |
Study information
| Verified date |
December 2021 |
| Source |
Assistance Publique - Hôpitaux de Paris |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial 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.
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.
