Alcohol WithdrawalPhase 2/3AToM1NCT03466528
Alcohol: Thiamine and or Magnesium 1
A Phase 2/3 study testing Magnesium Sulfate and Pabrinex in people with Alcohol Withdrawal and Lactic Acidosis, run by Glasgow Royal Infirmary at 1 site in United Kingdom.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 100 years
- Conditions the study is for
- Alcohol Withdrawal, Lactic Acidosis, Vitamin B1 Deficiency
- What is being tested?
- Magnesium Sulfate and Pabrinex
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 127 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 16 Dec 2016to 19 Jun 2018
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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 locations and contacts
1 site in 1 country.
About this study
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
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.
- Conditions
- Alcohol Withdrawal, Lactic Acidosis, Vitamin B1 Deficiency, Magnesium Deficiency, Wernicke Encephalopathy
- Being tested
- Magnesium Sulfate, Pabrinex
- Medical subject headings
- Acidosis, Lactic, Beriberi, Magnesium Deficiency, Wernicke Encephalopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Magnesium SulfateDrug
Also called MgSO4
Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes
PabrinexDrug
Also called comercial form of thiamine and B vitamin preparation
standard treatment
| Study group | Role | What they receive |
|---|---|---|
| Standard treatment - Pabrinex alone | Active comparator | Pabrinex alone Receives: Drug: Pabrinex |
| Pabrinex + magnesium sulphate | Active comparator | standard treatment and magnesium sulphate Receives: Drug: Magnesium Sulfate; Drug: Pabrinex |
| Magnesium sulphate alone | Experimental | This group receives the study intervention and delayed Pabrinex Receives: Drug: Magnesium Sulfate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Erythrocyte transketolase activity
this is a biochemical marker of thiamine activity measured in units per gram of haemoglobin
Measured: 0 and 2 hours
Change in serum lactate
Biochemical marker of metabolic dysfunction (expressed as mmol/L)
Measured: 0 and 2 hours
Change in rate of resolution of alcohol withdrawal syndrome
time
Measured: days
Secondary outcomes (4)
lactate dehydrogenase
biochemical (expressed in mmol/L)
Measured: 0 and 2 hours
pre and post magnesium
biochemical (expressed in mmol/L)
Measured: 0 and 2 hours
pre and post red cell thiamine
biochemical
Measured: 0 and 2 hours
establish baseline micronutrient status of patients with alcohol withdrawal syndrome
biochemical
Measured: o and 2 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Mar 2018
- Study start16 Dec 2016
- Primary completion2 Apr 2018
- Study completion19 Jun 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Alcohol WithdrawalStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- None (open label)
- Enrolment
- 127 participants (actual)
Sponsor and investigators
- Lead sponsor
- Glasgow Royal Infirmary
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Dr. Donogh Maguire, Glasgow Royal Infirmary
- Investigators
- Donogh Maguire, MB BCh, Principal investigator, NHS GGC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03466528
- Sponsor's protocol ID
- GN16ME174
- Other IDs
- 201773
- Acronym
- AToM1
- Status last verified
- Jul 2019
- First submitted
- 13 Feb 2018
- Last updated
- 31 Jul 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
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 at a glance
From the registry record, last updated by the sponsor on 31 Jul 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT03466528
- Acronym / sponsor ID
- AToM1 / GN16ME174
- Conditions
- Alcohol Withdrawal, Lactic Acidosis, Vitamin B1 Deficiency, Magnesium Deficiency, Wernicke Encephalopathy
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 127 participants (actual)
- Lead sponsor
- Glasgow Royal InfirmaryUniversity, hospital or other
- Study start
- 16 Dec 2016 (actual)
- Primary completion
- 2 Apr 2018 (actual)
- Study completion
- 19 Jun 2018 (actual)
- First posted
- 15 Mar 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- 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.
| Arm | Type | Receives |
|---|---|---|
| Standard treatment - Pabrinex alone | Active comparator | Drug: PabrinexPabrinex alone |
| Pabrinex + magnesium sulphate | Active comparator | Drug: Magnesium Sulfate, Drug: Pabrinexstandard treatment and magnesium sulphate |
| Magnesium sulphate alone | Experimental | Drug: Magnesium SulfateThis group receives the study intervention and delayed Pabrinex |
Who may qualify
- Ages
- 18 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (5 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Magnesium SulfateAlso: MgSO4Intravenous (Magnesium Sulphate) MgSO4 2 grams IV over 20 minutes | Drug | Magnesium sulphate alone, Pabrinex + magnesium sulphate |
| PabrinexAlso: comercial form of thiamine and B vitamin preparationstandard treatment | Drug | Pabrinex + magnesium sulphate, Standard treatment - Pabrinex alone |
Primary outcome
Change in Erythrocyte transketolase activity
Time frame: 0 and 2 hours
this is a biochemical marker of thiamine activity measured in units per gram of haemoglobin
Change in serum lactate
Time frame: 0 and 2 hours
Biochemical marker of metabolic dysfunction (expressed as mmol/L)
Change in rate of resolution of alcohol withdrawal syndrome
Time frame: days
time
4 secondary outcomes
lactate dehydrogenase
Time frame: 0 and 2 hours
pre and post magnesium
Time frame: 0 and 2 hours
pre and post red cell thiamine
Time frame: 0 and 2 hours
establish baseline micronutrient status of patients with alcohol withdrawal syndrome
Time frame: o and 2 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Jul 2019.
- Derived from this study: PubMed 35484175Maguire 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Donogh Maguire, MB BCh principal investigator
NHS GGC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Magnesium Sulfate and Pabrinex in people with Alcohol Withdrawal and Lactic Acidosis, run by Glasgow Royal Infirmary at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 31 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Erythrocyte transketolase activity (time frame: 0 and 2 hours). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03466528, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jul 2019.