Optimum Thiamine Intervention (OpTIn) Trial

Brief Title

Optimum Thiamine Intervention (OpTIn) Trial

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 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
    

Study Phase

Phase 4

Study Type

Interventional


Primary Outcome

Standardised Cognitive assessment - RUDAS

Secondary Outcome

 Blood thiamine levels

Condition

Wernicke-Korsakoff Syndrome

Intervention

Thiamine Hydrochloride

Study Arms / Comparison Groups

 Acute Symptomatic WKS- 300mg
Description:  Thiamine Hydrochloride 300mg daily (i.e. 100mg 3 times/day) for 5 days

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

334

Start Date

September 2014

Completion Date

August 1, 2019

Primary Completion Date

May 30, 2019

Eligibility Criteria

        Inclusion Criteria:

          -  Aged range 18-65 years

          -  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

          -  Renal dialysis patients

          -  Sedated patients in ICU
      

Gender

All

Ages

18 Years - 65 Years

Accepts Healthy Volunteers

No

Contacts

Kylie Dingwall, PhD, , 

Location Countries

Australia

Location Countries

Australia

Administrative Informations


NCT ID

NCT02788552

Organization ID

2014-08-27_Version2.1

Secondary IDs

ACTRN12614000327684

Responsible Party

Sponsor

Study Sponsor

Menzies School of Health Research


Study Sponsor

Kylie Dingwall, PhD, Principal Investigator, Menzies School of Health Research


Verification Date

August 2019