Alcohol: Thiamine and or Magnesium 1

Phase 2

Completed

• Conditions: Vitamin B1 Deficiency; Alcohol Withdrawal; Lactic Acidosis; Wernicke Encephalopathy; Magnesium Deficiency
• Interventions: Drug: Pabrinex; Drug: Magnesium Sulfate

• Registration Number: NCT03466528
• Lead Sponsor: Glasgow Royal Infirmary

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.

Study Timeline

• Study Start: 2016-12-16
• Study First Submitted: 2018-02-13
• Study First Submitted QC: 2018-03-08
• Study First Posted: 2018-03-15
• Primary Completion: 2018-04-02
• Study Completion: 2018-06-19
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-29
• Last Update Posted: 2019-07-31

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 127

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard treatment - Pabrinex alone	Pabrinex	Pabrinex alone
Pabrinex + magnesium sulphate	Pabrinex	standard treatment and magnesium sulphate
Pabrinex + magnesium sulphate	Magnesium Sulfate	standard treatment and magnesium sulphate
Magnesium sulphate alone	Magnesium Sulfate	This group receives the study intervention and delayed Pabrinex

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Glasgow Royal Infirmary; 🇬🇧 Glasgow, United Kingdom