Alcohol: Thiamine and or Magnesium 1 (AToM1)

Glasgow Royal Infirmary

Status and phase: Completed; Phase 3; Phase 2

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

Treatments: Drug: Pabrinex; Drug: Magnesium Sulfate

Study type: Interventional

Funder types: Other

Identifiers

NCT03466528

201773

GN16ME174

Details and patient eligibility

About

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.

Full 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.

Enrollment: 127 patients

Sex: All

Ages: 18 to 100 years old

Volunteers: No 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

127 participants in 3 patient groups

Standard treatment - Pabrinex alone

Active Comparator group

Description:

Pabrinex alone

Treatment:

Drug: Pabrinex

Pabrinex + magnesium sulphate

Active Comparator group

Description:

standard treatment and magnesium sulphate

Treatment:

Drug: Magnesium Sulfate

Drug: Pabrinex

Magnesium sulphate alone

Experimental group

Description:

This group receives the study intervention and delayed Pabrinex

Treatment:

Drug: Magnesium Sulfate