Clinical trial NCT03466528: Alcohol: Thiamine and or Magnesium 1
Official title: A Prospective Randomised Controlled Trial of the Effect of Magnesium Sulphate Administration on Red Cell Transketolase Activity in Alcohol Dependent Patients at Risk of Wernicke Korsakoff Syndrome Treated With Thiamine
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Alcohol Withdrawal
Lactic Acidosis
Vitamin B1 Deficiency
Magnesium Deficiency
Wernicke Encephalopathy
Lead sponsor: Glasgow Royal Infirmary
Sponsor class: OTHER
First posted: 2018-03-15
Enrollment: 127
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a 3- arm randomised, open label, controlled study in a cohort of alcoholic patients admitted through A\&E. Patients will be randomised to concurrent infusion of one of the following:

* Arm 1: IV thiamine
* Arm 2: IV magnesium sulphate followed by delayed IV thiamine
* Arm 3: IV thiamine and IV magnesium sulphate Thiamine will be administered as IV Pabrinex, a compound preparation which also contains B vitamins and vitamin C. Administration of IV Pabrinex is standard care in this patient group and magnesium sulphate is routinely co-administered at Glasgow Royal Infirmary.
Primary purpose: TREATMENT

Brief summary: Patients who suffer Alcohol Use Disorder (AUD) have a 30-80% incidence of thiamine deficiency causing Wernicke's Encephalopathy (WE).

Intravenous (IV) thiamine replacement is standard practice in the treatment of alcoholic patients presenting to the Accident \& Emergency (A\&E) department, however routine co-supplementation with magnesium (administered IV as magnesium sulphate ), which is required as a co-factor for thiamine in some metabolic processes, e. g. on the activity of the enzyme transketolase in red blood cells, is not routine practice in the treatment of these patients. Without correction of concomitant magnesium deficiency there may be impaired utilisation of thiamine resulting in a failure to treat WE.

This study is designed to determine if administration of magnesium to AUD patients affects red cell transketolasae and serum lactate concentrations by itself, or only acts to increase the effect of thiamine on the activity of this enzyme.

Detailed description: This is a 3- arm randomised, open label, controlled study in a cohort of alcoholic patients admitted through A\&E. Patients will be randomised to concurrent infusion of one of the following:

* Arm 1: IV thiamine
* Arm 2: IV magnesium sulphate followed by delayed IV thiamine
* Arm 3: IV thiamine and IV magnesium sulphate Thiamine will be administered as IV Pabrinex, a compound preparation which also contains B vitamins and vitamin C. Administration of IV Pabrinex is standard care in this patient group and magnesium sulphate is routinely co-administered at Glasgow Royal Infirmary.

Eligibility criteria: Inclusion Criteria:

* Written informed consent
* Male or non-pregnant or breastfeeding females ≥18 years of age For women of child-bearing potential a negative pregnancy test will be required prior to treatment.

(Women of non-childbearing potential are defined as those defined as women who are post-menopausal or permanently sterilised (e.g. hysterectomy, tubal occlusion, bilateral salpingectomy).

• Chronic alcohol dependence as confirmed by

* FAST questionnaire
* GMAWS scale

Exclusion Criteria:

* Unable to give consent
* Less than 18 years of age
* Chronic renal or hepatic failure/hepatic encephalopathy (investigator assessment as documented in past medical history i.e. Clinical Portal.)
* Known hypersensitivity or previous allergy to any of the active substances in either trial medication, or to excipients
* Severe concurrent medical condition that would prevent participation in study procedures (e.g. myasthenia gravis, clinically significant cardiac disease, or cardiac failure with severe pulmonary oedema)

Primary outcomes:
measure: Change in Erythrocyte transketolase activity
timeFrame: 0 and 2 hours
measure: Change in serum lactate
timeFrame: 0 and 2 hours
measure: Change in rate of resolution of alcohol withdrawal syndrome
timeFrame: days
Secondary outcomes:
measure: lactate dehydrogenase
timeFrame: 0 and 2 hours
measure: pre and post magnesium
timeFrame: 0 and 2 hours
measure: pre and post red cell thiamine
timeFrame: 0 and 2 hours
measure: establish baseline micronutrient status of patients with alcohol withdrawal syndrome
timeFrame: o and 2 hours
Other outcomes:
Locations:
city: Glasgow
country: United Kingdom
facility: Glasgow Royal Infirmary
Study officials:
affiliation: NHS GGC
name: Donogh Maguire, MB BCh
role: PRINCIPAL_INVESTIGATOR
References:
citation: Maguire D, Burns A, Talwar D, Catchpole A, Stefanowicz F, Ross DP, Galloway P, Ireland A, Robson G, Adamson M, Orr L, Kerr JL, Roussis X, Colgan E, Forrest E, Young D, McMillan DC. Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores. Sci Rep. 2022 Apr 28;12(1):6941. doi: 10.1038/s41598-022-10970-x.