Optimum Thiamine Intervention (OpTIn) Trial

Menzies School of Health Research

Status and phase: Completed; Phase 4

Conditions: Wernicke-Korsakoff Syndrome

Treatments: Drug: Thiamine Hydrochloride

Study type: Interventional

Funder types: Other

Identifiers

NCT02788552

ACTRN12614000327684 (Registry Identifier)

2014-08-27_Version2.1

Project Grant GNT1057968 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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

Enrollment: 334 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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334 participants in 6 patient groups

Acute Symptomatic WKS- 300mg

Active Comparator group

Description:

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

Treatment:

Drug: Thiamine Hydrochloride

Acute Symptomatic WKS - 900mg

Active Comparator group

Description:

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

Treatment:

Drug: Thiamine Hydrochloride

Acute Symptomatic WKS - 1500mg

Active Comparator group

Description:

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

Treatment:

Drug: Thiamine Hydrochloride

High-risk subclinical WKS- 100mg

Active Comparator group

Description:

Thiamine Hydrochloride 100mg once daily for 3 days.

Treatment:

Drug: Thiamine Hydrochloride

High-risk subclinical WKS- 300mg

Active Comparator group

Description:

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

Treatment:

Drug: Thiamine Hydrochloride

High-risk subclinical WKS - 900mg

Active Comparator group

Description:

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

Treatment:

Drug: Thiamine Hydrochloride