Optimum Thiamine Intervention (OpTIn) Trial

Sponsor
Menzies School of Health Research (Other)
Overall Status
Completed
CT.gov ID
NCT02788552
Collaborator
(none)
334
1
6
59
5.7

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
  • Drug: Thiamine Hydrochloride
Phase 4

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:
  1. Treatment of acute symptomatic WKS among Aboriginal and non-Aboriginal alcohol dependent patients.

  2. 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 Design

Study Type:
Interventional
Actual Enrollment :
334 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Single (Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
Optimum Thiamine Intervention (OpT In) for Treatment and Prevention of Wernicke-Korsakoff Syndrome (WKS): A Randomised Controlled Trial
Study Start Date :
Sep 1, 2014
Actual Primary Completion Date :
May 30, 2019
Actual Study Completion Date :
Aug 1, 2019

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Acute Symptomatic WKS- 300mg

Thiamine Hydrochloride 300mg daily (i.e. 100mg 3 times/day) for 5 days

Drug: Thiamine Hydrochloride
Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Active Comparator: Acute Symptomatic WKS - 900mg

    Thiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 5 days

    Drug: Thiamine Hydrochloride
    Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
    Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Active Comparator: Acute Symptomatic WKS - 1500mg

    Thiamine Hydrochloride 1500mg daily (i.e. 500mg 3 times/day) for 5 days.

    Drug: Thiamine Hydrochloride
    Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
    Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Active Comparator: High-risk subclinical WKS- 100mg

    Thiamine Hydrochloride 100mg once daily for 3 days.

    Drug: Thiamine Hydrochloride
    Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
    Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Active Comparator: High-risk subclinical WKS- 300mg

    Thiamine Hydrochloride 300mg (i.e. 100mg 3 time/day) for 3 days

    Drug: Thiamine Hydrochloride
    Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
    Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Active Comparator: High-risk subclinical WKS - 900mg

    Thiamine Hydrochloride 900mg daily (i.e. 300mg 3 times/day) for 3 days.

    Drug: Thiamine Hydrochloride
    Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.
    Other Names:
  • Vitamin B1
  • Thiamine Chloride
  • Aneurine Hydrochloride
  • B Complex Vitamin
  • Outcome Measures

    Primary Outcome Measures

    1. Standardised Cognitive assessment - RUDAS [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 assessment - Rowland Universal Dementia Assessment Scale (RUDAS).

    2. Standardised Cognitive assessment - CogState [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 CogState battery.

    3. Standardised Cognitive assessment - Story Memory Recall Test [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 Story Memory Recall test

    4. Standardised neurological examination [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. Aggregated as either normal or abnormal.

    Secondary Outcome Measures

    1. Blood thiamine levels [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).

    2. Magnesium levels [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).

    3. Demographic factors [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.

    4. Readmission [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)

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Alice Springs Hospital Alice Springs Northern Territory Australia 0810

    Sponsors and Collaborators

    • Menzies School of Health Research

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Menzies School of Health Research
    ClinicalTrials.gov Identifier:
    NCT02788552
    Other Study ID Numbers:
    • 2014-08-27_Version2.1
    • ACTRN12614000327684
    • Project Grant GNT1057968
    First Posted:
    Jun 2, 2016
    Last Update Posted:
    Aug 16, 2019
    Last Verified:
    Aug 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Menzies School of Health Research
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Aug 16, 2019