None listed
Conditions
Brief summary
Wernicke-Korsakoff syndrome (WKS), once thought to be a rare condition, is now known to be common in people with nutritional deficiencies or alcohol dependence. The primary cause of WKS is thiamine deficiency, and more than 90% of cases are reported in alcohol dependent patients because alcohol dependence predisposes to severe nutritional deficiency. WKS may lead to significant, long-term brain dysfunction with severe effects on work, personal and social function. Whilst effective treatment may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens. This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal setting. The need for evidence-based thiamine treatment protocols is of great clinical importance for two related reasons. First, in relation to acute symptomatic WKS, a failure to treat immediately or adequately may result in profound and often permanent cognitive and neurological disability. Secondly, the need for evidence-based treatment guidelines is greatly magnified when it is recognised that milder, subclinical WKS may be preventable with adequate thiamine treatment. The aims of this study are to determine the optimal thiamine dose required for: A. Treatment of acute symptomatic Wernicke-Korsakoff syndrome (WKS) among Aboriginal and non-Aboriginal alcohol-dependent patients. B. Reducing or preventing subclinical WKS-related brain damage in at-risk Aboriginal and non-Aboriginal alcohol-dependent patients. Primary Hypotheses 1. Among alcohol-dependent patients with acute symptomatic WKS, higher doses of parenteral thiamine (1500mg) will lead to greater improvements in specific cognition and neurological functions than lower doses (900mg or 300mg). 2. Among alcohol-dependent patients that are at high risk for subclinical WKS-related brain damage, higher doses of parenteral thiamine (900mg) will lead to greater improvements in specific cognition and neurological functions compared to lower doses (300mg or 100mg). Secondary Hypotheses 1. Thiamine deficient patients will show poorer performance on cognitive and neurological measures 2. Patients with concurrent magnesium deficiency will show greater impairment at baseline 3. Nutritional risk and alcohol frequency will correlate with thiamine pyrophosphate levels. 4. Number of previous admissions with thiamine supplementation in the past 3 months will correlate with thiamine pyrophosphate levels.
Interventions
Thiamine Hydrochloride
On the first day of the trial, following baseline assessment, participants will be randomised to one of three parenteral thiamine dose conditions.
Acute Symptomatic WKS Group:
i. 300mg daily (i.e. 100mg 3 times/day) for 5 days
ii. 900mg daily (i.e. 300mg 3 times/day) for 5 days or
iii. 1500mg daily (i.e. 500mg 3 times/day) for 5 days.
High-risk of subclinical WKS-related brain damage:
i. 100mg once daily for 3 days,
ii. 300mg (i.e. 100mg 3 times/day) for 3 days or
ii
Thiamine Hydrochloride On the first day of the trial, following baseline assessment, participants will be randomised to one of three parenteral thiamine dose conditions. Acute Symptomatic WKS Group: i. 300mg daily (i.e. 100mg 3 times/day) for 5 days ii. 900mg daily (i.e. 300mg 3 times/day) for 5 days or iii. 1500mg daily (i.e. 500mg 3 times/day) for 5 days. High-risk of subclinical WKS-related brain damage: i. 100mg once daily for 3 days, ii. 300mg (i.e. 100mg 3 times/day) for 3 days or iii. 900mg (i.e. 300mg 3 times/day) for 3 days. Thiamine Hydrochloride will be prescribed by the Addiction Medicine physician (also a trial Investigator) using standard hospital prescribing. The thiamine will be provided by the hospital pharmacy and administered by the registered nurse caring for the patient. Administration will be intravenously in a 100ml bag of normal saline (0.9%) infused over 30 minutes. Adherence will be recorded by reviewing medication chart.
Sponsors
Dr Kylie Dingwall
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
Aged between 18-65 History of heavy alcohol use AUDIT-C score >4 or consumption >60mg/day or >80mg/binge
Exclusion criteria
Pregnant women. Under the age of 18 or over 65 years old Known pre-existing neurological or cognitive impairment unrelated to thiamine deficiency or WKS. Intubated on vasopressor therapy for hypotension on Renal dialysis
Outcome results
None listed