Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Optimum Thiamine Intervention (OpTIn) Trial (OpTIn)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02788552
Recruitment Status : Completed
First Posted : June 2, 2016
Last Update Posted : August 16, 2019
Sponsor:
Information provided by (Responsible Party):
Menzies School of Health Research

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
Wernicke-Korsakoff Syndrome 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:

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
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 : September 2014
Actual Primary Completion Date : May 30, 2019
Actual Study Completion Date : August 1, 2019


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




Primary Outcome Measures :
  1. Standardised Cognitive assessment - RUDAS [ 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 assessment - Rowland Universal Dementia Assessment Scale (RUDAS).

  2. Standardised Cognitive assessment - CogState [ 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 CogState battery.

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

  4. 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. Aggregated as either normal or abnormal.


Secondary Outcome Measures :
  1. 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).

  2. 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).

  3. 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.

  4. 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)



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02788552


Locations
Layout table for location information
Australia, Northern Territory
Alice Springs Hospital
Alice Springs, Northern Territory, Australia, 0810
Sponsors and Collaborators
Menzies School of Health Research
Investigators
Layout table for investigator information
Principal Investigator: Kylie Dingwall, PhD Menzies School of Health Research

Layout table for additonal information
Responsible Party: Menzies School of Health Research
ClinicalTrials.gov Identifier: NCT02788552     History of Changes
Other Study ID Numbers: 2014-08-27_Version2.1
ACTRN12614000327684 ( Registry Identifier: ANZCTR )
Project Grant GNT1057968 ( Other Grant/Funding Number: NHMRC )
First Posted: June 2, 2016    Key Record Dates
Last Update Posted: August 16, 2019
Last Verified: August 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Menzies School of Health Research:
Neurological
Diet and Nutrition
Mental Health

Additional relevant MeSH terms:
Layout table for MeSH terms
Syndrome
Wernicke Encephalopathy
Korsakoff Syndrome
Disease
Pathologic Processes
Brain Diseases, Metabolic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Metabolic Diseases
Thiamine Deficiency
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Alcohol-Related Disorders
Substance-Related Disorders
Chemically-Induced Disorders
Mental Disorders
Memory Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Signs and Symptoms
Vitamins
Thiamine
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs