AToM1: Alcohol: Thiamine and or Magnesium 1

Sponsor

Glasgow Royal Infirmary (Other)

Overall Status

Completed

CT.gov ID

NCT03466528

Collaborator

(none)

127

Enrollment

Location

Arms

18.1

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Alcohol Withdrawal Lactic Acidosis Vitamin B1 Deficiency Magnesium Deficiency Wernicke Encephalopathy	Drug: Magnesium Sulfate Drug: Pabrinex	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

127 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

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.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)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Dec 16, 2016

Actual Primary Completion Date :

Apr 2, 2018

Actual Study Completion Date :

Jun 19, 2018

Arms and Interventions

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

Arm

Intervention/Treatment

Active Comparator: Standard treatment - Pabrinex alone

Pabrinex alone

Drug: Pabrinex

standard treatment

Other Names:

comercial form of thiamine and B vitamin preparation

Active Comparator: Pabrinex + magnesium sulphate

standard treatment and magnesium sulphate

Drug: Magnesium Sulfate

Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes

Other Names:

MgSO4

Drug: Pabrinex

standard treatment

Other Names:

comercial form of thiamine and B vitamin preparation

Experimental: Magnesium sulphate alone

This group receives the study intervention and delayed Pabrinex

Drug: Magnesium Sulfate

Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes

Other Names:

MgSO4

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 100 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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)