Not Yet RecruitingPhase 2ACTRN12625001249448

Alternative Fuels for Traumatic Brain Injury project (Phase 2)

Open-label Pilot Randomised Controlled Trial of Enteric R-1,3 Butanediol in Moderate to Severe Traumatic Brain Injury to assess feasibility.

Sponsor

East Metropolitan Health Service

Enrollment

30 participants

Start Date

Feb 16, 2026

Study Type

Interventional

Conditions

Traumatic Brain Injury

Summary

This research program is studying whether giving ketone nutritional supplements to traumatic brain injury (TBI) patients can improve outcomes. To begin this line of research, this project will identify the optimal supplement dose for patients in the intensive care unit and examine the feasibility of using these supplements in TBI patients. Previous studies have used single doses of the supplement in relatively healthy patients. This study will be the first to look at the effect of giving multiple doses of the ketone supplement to critically ill intensive care unit patients. Information obtained from this study is foundational for planned future trials examining the use of ketone supplements in critically ill patients.

Eligibility

Sex: Both males and femalesMin Age: 18 YearssMax Age: 80 Yearss

Inclusion Criteria5

Clinical diagnosis of moderate to severe traumatic brain injury (TBI) (Glasgow Coma Score (GCS) of 12 or lower post-traumatic injury requiring invasive neuromonitoring).
Expected to remain intubated for more than 48 hours due to traumatic injuries
Radiological (Computed Tomography (CT)) evidence of traumatic brain parenchymal injury (contusion, Subdural haematoma, Subarachnoid Haemorrhage, and/or Diffuse Axonal Injury)
ICM+ software (Cambridge, UK) data recording available
Able to commence the study protocol within 24 hours of injury

Exclusion Criteria12

Contraindication for administration of enteral feeding and/or medications
Use of Parenteral Nutrition (PN)
High Anion Gap Metabolic Acidosis defined by pH less than 7.20, PaCO2 less than 45 mm Hg, and sodium bicarbonate less than 20 mmol/L
Bilateral fixed and dilated pupils and/or deemed to be non-survivable by treating clinical team
Brainstem injury or concomitant severe high spinal cord injury (C1 to C3)
Pre-existing end-stage renal failure, Child-Pugh B or C liver disease, or known history of Glucose-6-phosphodiesterase deficiency
Cardiac arrest with probable concomitant hypoxic brain injury
Confirmed or suspected pregnancy
Type 1 diabetic / insulin-dependent diabetes
Stress-induced hyperglycaemia requiring more than 10 U/hr insulin
History of recent SGLT-2 inhibitors use (within previous 48 hours)
Renal replacement therapy in use

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Interventions

Phase 2 is submitted in this application. Phase 1 has been split onto application 390435. Phase 2 ia a feasibility study Phase 2 will commence after the Phase 1 dosing study data is analysed and an

Phase 2 is submitted in this application. Phase 1 has been split onto application 390435. Phase 2 ia a feasibility study Phase 2 will commence after the Phase 1 dosing study data is analysed and an optimal dose is identified. There will be 30 patients in Phase 2 (15 in each arm). Phase 1 participants will not be used in Phase 2. All patients will be heavily sedated and intubated. The enteral route used will be that which is available. Clinical teams variably place nasogastric (most common), orogastric, and nasojejunal (less common) feeding tubes. Whichever of these are available will be used. Rarely, patients may be extubated sooner than anticipated and may be able to swallow. If this happens and it is safe to do so, they can drink the intervention. We will monitor the patient's medication chart and electronic records, as well as the consumption of R-1,3-butanediol stock.. Optimal dose will be identified in Phase 1 of this project The doses to be investigated in Phase 1 will be • 0.5 g/kg Adjusted body weight (AjBW) R-1,3-Butanediol every 8 hours enterally for 4 days • 0.4 g/kg AjBW R-1,3-Butanediol every 6 hours enterally for 4 days • 0.6 g/kg AjBW R-1,3-Butanediol every 8 hours enterally for 4 days • 0.5 g/kg AjBW R-1,3-Butanediol every 6 hours enterally for 4 days These will be tested in 12 patients (3 in each group), and the dosing regimen that provides the best combination of a) ketone plasma level (AUC) and b) minimal side effects will be used in Phase 2 (n=30). Phase 2 will be commenced after review of Phase 1 data. 'Enteral route' refers to oral, nasogastric, nasojejunal, and orogastric routes.