Optimum Thiamine Intervention (OpTIn) Trial

NCT02788552 | Completed Phase 4

• 3 other identifiers: 2014-08-27_Version2.1ACTRN12614000327684Project Grant GNT1057968
• Study Type: interventional
• Target: 334
• Locations: 1 country
• Sites: 1

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.

Conditions

Wernicke-Korsakoff Syndrome

Keywords

Neurological; Diet and Nutrition; Mental Health

Outcome Measures

Primary Outcomes (4)

• Standardised Cognitive assessment - RUDAS

  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).

  Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients

• Standardised Cognitive assessment - CogState

  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.

  Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients

• Standardised Cognitive assessment - Story Memory Recall Test

  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

  Days 1 and 5 for Acute symptomatic patients and Days 1 and 3 for at risk patients

• Standardised neurological examination

  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.

  Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients

Secondary Outcomes (4)

• Blood thiamine levels

  Days 1 and 5 for acute symptomatic patients; days 1 and 3 for at risk patients

• Magnesium levels

  Days 1 and 5 for acute symptomatic patients; Days 1 and 3 for at risk patients

• Demographic factors

  Day 1

• Readmission

  Day 1

Study Arms (6)

Acute Symptomatic WKS- 300mg

ACTIVE COMPARATOR

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

Drug: Thiamine Hydrochloride

Acute Symptomatic WKS - 900mg

ACTIVE COMPARATOR

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

Drug: Thiamine Hydrochloride

Acute Symptomatic WKS - 1500mg

ACTIVE COMPARATOR

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

Drug: Thiamine Hydrochloride

High-risk subclinical WKS- 100mg

ACTIVE COMPARATOR

Thiamine Hydrochloride 100mg once daily for 3 days.

Drug: Thiamine Hydrochloride

High-risk subclinical WKS- 300mg

ACTIVE COMPARATOR

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

Drug: Thiamine Hydrochloride

High-risk subclinical WKS - 900mg

ACTIVE COMPARATOR

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

Drug: Thiamine Hydrochloride

Interventions

Thiamine Hydrochloride DRUG

Administered Intravenously in 100ml bag of normal saline (0.9%) infused over 30 mins.

Also known as: Vitamin B1, Thiamine Chloride, Aneurine Hydrochloride, B Complex Vitamin

Acute Symptomatic WKS - 1500mg; Acute Symptomatic WKS - 900mg; Acute Symptomatic WKS- 300mg; High-risk subclinical WKS - 900mg; High-risk subclinical WKS- 100mg; High-risk subclinical WKS- 300mg

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged range 18-65 years
• History of heavy alcohol use AUDIT-C score \>4 or consumption \>60mg/day or \>80mg/binge

You may not qualify if:

• 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

Sponsors & Collaborators

• Menzies School of Health Research: lead

Study Sites (1)

Alice Springs Hospital

Alice Springs, Northern Territory, 0810, Australia

Location

MeSH Terms

Conditions

Korsakoff Syndrome; Neurologic Manifestations; Psychological Well-Being

Interventions

thiamine hydrochloride; Thiamine; Vitamin B Complex

Condition Hierarchy (Ancestors)

Memory Disorders; Neurobehavioral Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Personal Satisfaction; Behavior

Intervention Hierarchy (Ancestors)

Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Vitamins; Micronutrients; Physiological Effects of Drugs; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Kylie Dingwall, PhD

  Menzies School of Health Research

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 26, 2014
• First Posted: June 2, 2016
• Study Start: September 1, 2014
• Primary Completion: May 30, 2019
• Study Completion: August 1, 2019
• Last Updated: August 16, 2019

Record last verified: 2019-08

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)