Exogenous Ketone Supplementation in ICU Delirium
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorVanderbilt University Medical Center
About this trial
Delirium is a common syndrome in intensive care unit (ICU) patients. Those experiencing delirium may suddenly feel confused, have trouble thinking clearly, struggle to pay attention, or see and hear things that are not real. Delirium is associated with worse long-term outcomes such as cognitive impairment, depression, and PTSD (post-traumatic stress disorder). This study examines whether an investigational medical-grade ketone supplement drink (ketone monoester \[brand name: Ultrapure Ketone Monoester\]) is safe and feasible to use in ICU patients, and to look for signals that it might reduce delirium or shorten its duration compared to a volume-, taste-, and calorie-matched placebo.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Adult patients (≥18 years old) admitted to the medical intensive care unit.
Current ICU admission with anticipated ICU stay ≥24 hours.
Enteral access in place, planned enteral access placement, or PO intake appropriate, and the ability to receive enteral dosing within 24 hours of enrollment.
Ability to complete delirium assessments (CAM-ICU feasible) at time of enrollment.
Disqualifiers
Severe metabolic acidosis at screening: blood gas pH <7.20 or bicarbonate < 8 mmol/L.
Diabetic ketoacidosis as an ICU admission diagnosis or hyperketonemia from any ketoacidosis state.
Hypoglycemia as an ICU admission diagnosis or glucose <60 mg/dL.
Patients with a history of type 1 diabetes mellitus.
Trial design
Design model
Parallel
Treatments tested in this trial
Ketone monoester
DrugKetone monoester diluted to a total volume of 74 mL with water and administered enterally (oral/feeding tube). Dosing is protocolized with an initial dose of 25 g and subsequent dose titration based on serum β-hydroxybutyrate levels to target a prespecified serum β-hydroxybutyrate range, administered every 6 hours for up to 7 days (or ICU discharge or death, whichever occurs first).
Placebo
DrugPlacebo consists of 74 mL of dextrose 50% in water (D50W) plus 50 mg sucrose octaacetate for taste matching; administered enterally (oral/feeding tube) on the same schedule as the experimental arm.
Treatment groups
40 Participants
are divided into 2 treatment groupsGroup A: Ketone monoesterExperimental treatment 1 intervention
Group B: PlaceboPlacebo comparator 1 intervention
Trial outcomes
Primary outcomes
1
Mean composite Confusion Assessment Method for the Intensive Care Unit-7 (CAM-ICU-7) delirium severity score
Delirium severity will be assessed using the Confusion Assessment Method for the Intensive Care Unit-7 (CAM-ICU-7) delirium severity scale. The CAM-ICU-7 score ranges from 0 to 7, with higher scores indicating more severe delirium. A composite CAM-ICU-7 delirium severity score will be calculated for each participant by summing all available CAM-ICU-7 scores from enrollment through study day 7. The primary outcome will compare the mean composite CAM-ICU-7 delirium severity score between treatment arms. A clinically meaningful treatment effect is defined as a 25% lower mean composite CAM-ICU-7 score in the intervention arm compared with the control arm.
Time frame
From enrollment through study day 7.Secondary outcomes
1
Feasibility: Proportion of participants achieving target peak serum β-hydroxybutyrate (1.5-3.5 mmol/L) on at least 50% of dosing days
Peak serum β-hydroxybutyrate will be measured once daily using a post-dose blood draw collected 60-90 minutes after the morning ketone dose. A dosing day will be considered evaluable if a valid post-dose serum β-hydroxybutyrate measurement is obtained. A dosing day will be considered within target range if the post-dose serum β-hydroxybutyrate concentration is 1.5-3.5 mmol/L. This feasibility outcome is the proportion of ketone-group participants with post-dose serum β-hydroxybutyrate within the target range on at least 50% of evaluable dosing days. Feasibility will be considered met if at least 70% of ketone-group participants meet this criterion.
Time frame
From enrollment through study day 7 or ICU discharge.2
Feasibility: Proportion of scheduled post-dose serum β-hydroxybutyrate draws completed
The proportion of scheduled daily post-dose serum β-hydroxybutyrate draws that are successfully collected during the dosing period will be calculated and summarized. Feasibility performance will be summarized relative to a target of ≥80% completion.
Time frame
From enrollment through study day 7 or ICU discharge.3
Feasibility: Proportion of post-dose serum β-hydroxybutyrate measurements >4.0 mmol/L
In participants assigned to the ketone group, the proportion of valid daily post-dose serum β-hydroxybutyrate measurements greater than 4.0 mmol/L will be calculated during the dosing period. Performance will be summarized relative to a target of fewer than 10% of post-dose measurements greater than 4.0 mmol/L.
Time frame
From enrollment through study day 7 or ICU discharge.4
Safety and tolerability: Number of participants with ≥1 prespecified safety or tolerability event
A prespecified safety or tolerability event is defined as any of the following occurring from enrollment through study day 7: acid-base abnormality (blood gas pH \<7.20 or serum bicarbonate \<8 mmol/L), off-target hyperketonemia (peak serum β-hydroxybutyrate \>3.5 mmol/L despite dose reduction), hypoglycemia (\<60 mg/dL), renal or hepatic safety signal (new dialysis initiation; aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>5× upper limit of normal, or total bilirubin \>3 mg/dL without alternative explanation), or hemodynamic instability temporally related to dosing. Gastrointestinal symptoms (nausea, vomiting, diarrhea, cramping) will be reported separately as tolerability adverse events. The outcome will be summarized as the proportion of participants with ≥1 prespecified event by treatment arm.
Time frame
From enrollment through study day 7.Other outcomes
1
Change from baseline in serum interleukin-1 beta (IL-1β) concentration
Serum interleukin-1 beta (IL-1β) concentration will be measured at baseline and on study days 1, 3, 5, and 7 and reported as change from baseline by treatment arm.
Time frame
From enrollment through study day 7.2
Change from baseline in serum interleukin-6 (IL-6) concentration
Serum interleukin-6 (IL-6) concentration will be measured at baseline and on study days 1, 3, 5, and 7 and reported as change from baseline by treatment arm.
Time frame
From enrollment through study day 7.3
Change from baseline in serum interleukin-8 (IL-8) concentration
Serum interleukin-8 (IL-8) concentration will be measured at baseline and on study days 1, 3, 5, and 7 and reported as change from baseline by treatment arm.
Time frame
From enrollment through study day 7.4
Change from baseline in serum interleukin-10 (IL-10) concentration
Serum interleukin-10 (IL-10) concentration will be measured at baseline and on study days 1, 3, 5, and 7 and reported as change from baseline by treatment arm.
Time frame
From enrollment through study day 7.Sponsors and contacts
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Source ClinicalTrials.gov