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CompletedNCT03466528AToM1Updated Jul 31, 2019

Alcohol: Thiamine and or Magnesium 1

A Phase 2/3 interventional study of Magnesium Sulfate and Pabrinex in Alcohol Withdrawal, Lactic Acidosis and Vitamin B1 Deficiency, sponsored by Glasgow Royal Infirmary. Completed at 1 site in United Kingdom. Open to participants aged 18 Years to 100 Years. Per ClinicalTrials.gov, last updated 2019-07-31.

Sponsored by Glasgow Royal Infirmary · Phase 2/3, Interventional, and Treatment

Phase
Phase 2/3
Study type
Interventional
Enrollment
127
Allocation
Randomized
Ages
18 Years to 100 Years
Sex
All
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Study 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.

Read the 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.
02

Conditions studied

  • Alcohol Withdrawal
  • Lactic Acidosis
  • Vitamin B1 Deficiency
  • Magnesium Deficiency
  • Wernicke Encephalopathy
03

Who can participate

Ages eligible
18 Years to 100 Years
Sexes eligible
All
Accepts healthy volunteers
No

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

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)
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Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
127 participants (actual)

Study arms

  • Active comparator
    Standard treatment - Pabrinex alone

    Pabrinex alone

    Drug: Pabrinex

  • Active comparator
    Pabrinex + magnesium sulphate

    standard treatment and magnesium sulphate

    Drug: Magnesium Sulfate · Drug: Pabrinex

  • Experimental
    Magnesium sulphate alone

    This group receives the study intervention and delayed Pabrinex

    Drug: Magnesium Sulfate

Interventions

  • DrugMagnesium Sulfate

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

    Also known as: MgSO4

  • DrugPabrinex

    standard treatment

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

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What researchers measure

Primary outcomes

  1. Change in Erythrocyte transketolase activity

    this is a biochemical marker of thiamine activity measured in units per gram of haemoglobin

    Time frame: 0 and 2 hours

  2. Change in serum lactate

    Biochemical marker of metabolic dysfunction (expressed as mmol/L)

    Time frame: 0 and 2 hours

  3. Change in rate of resolution of alcohol withdrawal syndrome

    time

    Time frame: days

Secondary outcomes

  1. lactate dehydrogenase

    biochemical (expressed in mmol/L)

    Time frame: 0 and 2 hours

  2. pre and post magnesium

    biochemical (expressed in mmol/L)

    Time frame: 0 and 2 hours

  3. pre and post red cell thiamine

    biochemical

    Time frame: 0 and 2 hours

  4. establish baseline micronutrient status of patients with alcohol withdrawal syndrome

    biochemical

    Time frame: o and 2 hours

06

Study locations

1 site
  • Glasgow Royal Infirmary
    Glasgow, G4 0SF, United Kingdom
07

References and documents

Publications

  • 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. PubMed 35484175 ↗

Study documents

  • Informed consent form · Sep 21, 2016
  • Protocol and statistical analysis plan · Jul 13, 2016

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

08

Registry details

Key details

Study ID
NCT03466528
Lead sponsor
Glasgow Royal Infirmary
Responsible party
Dr. Donogh Maguire (Emergency Medicine Consultant, Glasgow Royal Infirmary) — Principal investigator
First posted
Mar 15, 2018
Start date
Dec 16, 2016
Primary completion
Apr 2, 2018
Completion
Jun 19, 2018
Last update
Jul 31, 2019

Study contacts

Donogh Maguire, MB BCh
principal investigator · NHS GGC

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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