Clinical Trial: Optimum Thiamine Intervention (OpTIn) Trial

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Optimum Thiamine Intervention (OpT In) for Treatment and Prevention of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial

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.

Detailed 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 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
    Sponsor: Menzies School of Health Research

    Current Primary Outcome:

    • Standardised Cognitive assessment [ Time Frame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients ]
      Evaluate differences in cognitive outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days); and among patients at high risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); using Standardised cognitive assessments.
    • Standardised neurological examination [ Time Frame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients ]
      Evaluate differences in neurological outcomes among acute symptomatic WKS patients under three parenteral thiamine treatment conditions (300mg/day for 5 days, versus 900mg/day for 5 days, versus 1500mg/day for 5 days);and among patients at high-risk of subclinical WKS-related brain damage under three parenteral thiamine treatment conditions (100mg/day for 3 days, versus 300mg/day for 3 days, versus 900mg/day for 3 days); Using Standardised neurological examination.


    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • Blood thiamine levels [ Time Frame: Days 1 and 5 for acute symptomatic patients; days 1 and 3 for at risk patients ]
      Correlate changes in red cell thiamine test results (blood test) with cognitive (standardised cognitive assessments score) and neurological functioning (standardised neurological examination).
    • Magnesium levels [ Time Frame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients ]
      Examine the impact of magnesium deficiency (magnesium blood test) on thiamine treatment response (cognition as measured by standardised cognitive assessments and thiamine pyrophosphate levels as measured by blood test).
    • Demographic factors [ Time Frame: Day 1 ]
      Assess independent predictors of WKS including nutritional factors, substance use history and demographic factors assessed by questionnaire items including Nutritional Risk Assessment and AUDIT-C.
    • Readmission [ Time Frame: Day 1 ]
      Examine the impact of patient re-admission on red cell thiamine pyrophosphate levels (blood test) and cognitive and neurological functioning (standardised cognitive and neurological assessments)


    Original Secondary Outcome: Same as current

    Information By: Menzies School of Health Research

    Dates:
    Date Received: September 26, 2014
    Date Started: September 2014
    Date Completion: December 2017
    Last Updated: May 26, 2016
    Last Verified: February 2016