Alcohol: Thiamine and or Magnesium 1

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Alcohol Withdrawal, Lactic Acidosis, Vitamin B1 Deficiency, Magnesium Deficiency, Wernicke Encephalopathy

Intervention / Treatment
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* Drug: Magnesium Sulfate
* Drug: Pabrinex


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Standard treatment - Pabrinex alone<br>Pabrinex alone | Drug: Pabrinex<br>* standard treatment<br>* Other names: comercial form of thiamine and B vitamin preparation;|
| Active Comparator: Pabrinex + magnesium sulphate<br>standard treatment and magnesium sulphate | Drug: Magnesium Sulfate<br>* Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes<br>* Other names: MgSO4;Drug: Pabrinex<br>* standard treatment<br>* Other names: comercial form of thiamine and B vitamin preparation;|
| Experimental: Magnesium sulphate alone<br>This group receives the study intervention and delayed Pabrinex | Drug: Magnesium Sulfate<br>* Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes<br>* Other names: MgSO4;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Erythrocyte transketolase activity | this is a biochemical marker of thiamine activity measured in units per gram of haemoglobin | 0 and 2 hours | 
| Change in serum lactate | Biochemical marker of metabolic dysfunction (expressed as mmol/L) | 0 and 2 hours | 
| Change in rate of resolution of alcohol withdrawal syndrome | time | days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| lactate dehydrogenase | biochemical (expressed in mmol/L) | 0 and 2 hours | 
| pre and post magnesium | biochemical (expressed in mmol/L) | 0 and 2 hours | 
| pre and post red cell thiamine | biochemical | 0 and 2 hours | 
| establish baseline micronutrient status of patients with alcohol withdrawal syndrome | biochemical | o and 2 hours |