Optimum Thiamine Intervention (OpTIn) Trial
Condition: Wernicke-Korsakoff Syndrome
MeSH terms: Wernicke Encephalopathy; Korsakoff Syndrome; Syndrome
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      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 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
    

Intervention name(s): Thiamine Hydrochloride
Intervention type(s): Drug
Intervention description(s): Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
Other intervention name(s): Vitamin B1; Thiamine Chloride; Aneurine Hydrochloride; B Complex Vitamin
Intervention MeSH terms: Vitamins; Thiamine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary purpose: Treatment
Keywords: Neurological; Diet and Nutrition; Mental Health