Clinical trial NCT02788552: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Wernicke-Korsakoff Syndrome
Keywords: Neurological
Diet and Nutrition
Mental Health
Lead sponsor: Menzies School of Health Research
Sponsor class: OTHER
First posted: 2016-06-02
Enrollment: 334
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Primary outcomes:
measure: Standardised Cognitive assessment - RUDAS
timeFrame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
measure: Standardised Cognitive assessment - CogState
timeFrame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
measure: Standardised Cognitive assessment - Story Memory Recall Test
timeFrame: Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients
measure: Standardised neurological examination
timeFrame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
Secondary outcomes:
measure: Blood thiamine levels
timeFrame: Days 1 and 5 for acute symptomatic patients; days 1 and 3 for at risk patients
measure: Magnesium levels
timeFrame: Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients
measure: Demographic factors
timeFrame: Day 1
measure: Readmission
timeFrame: Day 1
Other outcomes:
Locations:
city: Alice Springs
country: Australia
facility: Alice Springs Hospital
state: Northern Territory
Study officials:
affiliation: Menzies School of Health Research
name: Kylie Dingwall, PhD
role: PRINCIPAL_INVESTIGATOR
References: