Menzies’ postdoctoral research fellow, Dr Kylie Dingwall, was recently awarded a competitive grant as part of the National Health and Medical Research Council’s (NHMRC) yearly multi-million dollar funding round.

Kylie shares her thoughts on her new funding.

What is the title of your project?

Optimum thiamine dose for treatment and prevention of Wernicke-Korsakoff syndrome (WKS): a randomised controlled trial.

What major health issue does your research hope to address and how?

Alcohol dependence is a significant cause of morbidity and mortality among Indigenous and non-Indigenous Territorians.

Estimated per capita alcohol consumption is about 50 per cent higher in the Northern Territory (NT) than the national average. Alcohol-attributable deaths occur in the NT at around 3.5 times the rate observed nationwide and NT alcohol-attributable hospitalisations also greatly exceed those for the country as a whole.

Chronic alcohol use rapidly reduces levels of the nutrient thiamine (vitamin B1) among alcoholics, resulting in brain dysfunction, including Wernicke-Korsakoff syndrome (WKS). Once thought to be a rare condition, WKS is now known to be common in people with nutritional deficiencies or alcohol dependence.

WKS may lead to significant, long-term brain dysfunction with severe effects on work, and personal and social function.

Because the diagnosis of WKS is based on clinical judgement, it can be missed or misdiagnosed as alcohol intoxication or nonspecific alcohol-related dementia.

Clinical criteria traditionally required the full triad of symptoms for diagnosis of WKS: mental impairment, uncoordination and eye movement abnormalities.  However, revised criteria suggest that if at least one of the above signs occurs in conjunction with nutritional deficiency, a diagnosis of WKS should be made.

The cause of impairment is important for prognosis, because appropriate treatment is dependent on receiving an adequate thiamine dose promptly.

Incidence of WKS is approximately 1-2 per cent in postmortem surveys world-wide and only Alzheimer's disease and cerebrovascular disease are more common neurological disorders. Up to 80 per cent of alcohol-dependent people experience symptoms of thiamine deficiency.

Thiamine is essential for converting glucose to energy (glucose metabolism) and the brain requires a much greater amount of thiamine than other organs of the body.

Conditions that interfere with normal glucose metabolism, such as diabetes mellitus and renal dialysis, may therefore also be important contributors to thiamine deficiency, particularly among Aboriginal people where rates of these conditions are unacceptably high. The abovementioned risk factors for WKS are over-represented in the NT, suggesting that rates of WKS in the NT are also unacceptably high.

This project proposes to develop quality evidence for effective treatment of WKS in an Aboriginal and Torres Strait Islander setting. 

What is the most exciting aspect of your funding win?

Although appropriate and timely replenishment of thiamine is considered crucial to minimise brain damage and may greatly reduce severe disability and the human and social costs of this illness, almost no evidence exists on optimal dosing regimens for treating WKS.

In Australia, there are no national, evidence-based guidelines for the treatment or prevention of WKS and different clinical groups maintain diverse treatment protocols. 

The results of this study will provide new knowledge regarding the optimum dose for the treatment and prevention of WKS in an Indigenous health setting.

This evidence will inform the development of national best practice protocols for alcohol-related thiamine deficiency, leading to improved treatment and clinical management for an extremely vulnerable population.

What are the proposed details of your research methodology (sample numbers, sites etc)?

We will conduct two studies to determine the optimum daily thiamine dosing regimen for: (A) the treatment of acute symptomatic WKS (300 mg, 900 mg or 1500 mg of thiamine per day); and (B) the prevention of WKS-related brain damage in at-risk alcohol-dependent patients (100 mg, 300 mg or 900 mg of thiamine per day). We are aiming to recruit 225 participants per study.

What are the broader health implications of your grant?

Despite the high frequency of thiamine deficiency in alcohol-dependent, malnourished people, there is a lack of quality evidence regarding optimal treatment.

Treatment and prevention of brain dysfunction, through delivery of optimum thiamine dose, will improve these clients’ capacity to engage with their immediate medical self-management and achieve longer term behaviour change (e.g. reduced alcohol use).

What is the timeline for your project? 

The project will be completed over four years. Data collection for those at risk of WKS (Study B) is expected to be completed earlier than for those with symptoms of WKS (Study A) due to the higher expected recruitment rates based on numbers of likely presentations. 

What stakeholders or partners will the project involve?

Alice Springs Hospital and the University of Melbourne.

For more information on this area of work please click here.