None listed
Conditions
Brief 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. In this open-label phase 1 study, 12 patients at Royal Perth Hospital will be given one of 4 dosing regimens of the study intervention (R-1,3-butanediol) over 4 days. 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.
Interventions
Patients will be enrolled in sequential dose cohorts of 1.5, 1.6, 1.8 and 2.0 total daily g/kg. Each group will have 3 participants.
Dosing regimens:
• 0.4 g/kg Adjusted body weight (AjBW) R-1,3-Butanediol every 6 hours enterally for 4 days (1.6 g/kg daily)
• 0.6 g/kg AjBW R-1,3-Butanediol every 8 hours enterally for 4 days (1.8 g/kg daily)
• 0.5 g/kg AjBW R-1,3-Butanediol every 6 hours enterally for 4 days (2.0 g/kg daily)
'Enterally' refers to oral, nasogastric, nasojejunal and/or orogas
Patients will be enrolled in sequential dose cohorts of 1.5, 1.6, 1.8 and 2.0 total daily g/kg. Each group will have 3 participants. Dosing regimens: • 0.4 g/kg Adjusted body weight (AjBW) R-1,3-Butanediol every 6 hours enterally for 4 days (1.6 g/kg daily) • 0.6 g/kg AjBW R-1,3-Butanediol every 8 hours enterally for 4 days (1.8 g/kg daily) • 0.5 g/kg AjBW R-1,3-Butanediol every 6 hours enterally for 4 days (2.0 g/kg daily) 'Enterally' refers to oral, nasogastric, nasojejunal and/or orogastric administration as directed by the treating clinical team. The administration of R-1,3 butanediolh will be monitored using the patient's medication chart and electronic records, as well as by the consumption of R-1,3-butanediol stock.
Sponsors
East Metropolitan Health Service
Study design
Allocation
Non-randomised trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
• Admitted to the ICU following major trauma • Expected to remain intubated for more than 24 hours for management of injuries • Able to commence the study protocol within 48 hours of ICU admission • An arterial line is placed for clinical management
Exclusion criteria
• 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
Outcome results
None listed