Alcohol: Thiamine and or Magnesium 1

NCT03466528 | Completed Phase 2

• 2 other identifiers: GN16ME174201773
• Study Type: interventional
• Target: 127
• Locations: 1 country
• Sites: 1

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.

Conditions

Alcohol Withdrawal; Lactic Acidosis; Vitamin B1 Deficiency; Magnesium Deficiency; Wernicke Encephalopathy

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (4)

• lactate dehydrogenase

  0 and 2 hours

• pre and post magnesium

  0 and 2 hours

• pre and post red cell thiamine

  0 and 2 hours

• establish baseline micronutrient status of patients with alcohol withdrawal syndrome

  o and 2 hours

Study Arms (3)

Standard treatment - Pabrinex alone

ACTIVE COMPARATOR

Pabrinex alone

Drug: Pabrinex

Pabrinex + magnesium sulphate

ACTIVE COMPARATOR

standard treatment and magnesium sulphate

Drug: Magnesium Sulfate; Drug: Pabrinex

Magnesium sulphate alone

EXPERIMENTAL

This group receives the study intervention and delayed Pabrinex

Drug: Magnesium Sulfate

Interventions

Magnesium Sulfate DRUG

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

Also known as: MgSO4

Magnesium sulphate alone; Pabrinex + magnesium sulphate

Pabrinex DRUG

standard treatment

Also known as: comercial form of thiamine and B vitamin preparation

Pabrinex + magnesium sulphate; Standard treatment - Pabrinex alone

Eligibility Criteria

• Age: 18 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Glasgow Royal Infirmary: lead

Study Sites (1)

Glasgow Royal Infirmary

Glasgow, G4 0SF, United Kingdom

Location

Related Publications (1)

• 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.

  PMID: 35484175 DERIVED

MeSH Terms

Conditions

Acidosis, Lactic; Beriberi; Magnesium Deficiency; Wernicke Encephalopathy

Interventions

Magnesium Sulfate

Condition Hierarchy (Ancestors)

Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Thiamine Deficiency; Vitamin B Deficiency; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Brain Diseases, Metabolic; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Magnesium Compounds; Inorganic Chemicals; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds

Study Officials

• Donogh Maguire, MB BCh

  NHS GGC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Emergency Medicine Consultant

Model Details: 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 Record Dates

• First Submitted: February 13, 2018
• First Posted: March 15, 2018
• Study Start: December 16, 2016
• Primary Completion: April 2, 2018
• Study Completion: June 19, 2018
• Last Updated: July 31, 2019

Record last verified: 2019-07

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)