Recruiting
Phase 2

Ketone Monoester

Sponsor:

Vanderbilt University Medical Center

Code:

NCT07364162

Conditions

ICU Delirium

Critical Illness

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

Ketone monoester

Placebo

Study Details

Brief summary:

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.

Conditions

ICU Delirium

Critical Illness

Study ID

NCT07364162

Start date

Jun 9, 2026

Status verified date

Aug, 2026

Completion date

Dec 31, 2027

Anticipated

Primary completion date

Dec 31, 2026

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Inclusion criteria:

1. Adult patients (≥18 years old) admitted to the medical intensive care unit.
2. Current ICU admission with anticipated ICU stay ≥24 hours.
3. Enteral access in place, planned enteral access placement, or PO intake appropriate, and the ability to receive enteral dosing within 24 hours of enrollment.
4. Ability to complete delirium assessments (CAM-ICU feasible) at time of enrollment.

Exclusion criteria:

1. Severe metabolic acidosis at screening: blood gas pH <7.20 or bicarbonate < 8 mmol/L.
2. Diabetic ketoacidosis as an ICU admission diagnosis or hyperketonemia from any ketoacidosis state.
3. Hypoglycemia as an ICU admission diagnosis or glucose <60 mg/dL.
4. Patients with a history of type 1 diabetes mellitus.
5. Hemoglobin <7.0.
6. Fulminant hepatic failure or International Normalized Ratio (INR) > 3, when not attributable to therapeutic anticoagulation or another clearly non-hepatic cause.
7. Refractory shock, defined as a sustained norepinephrine requirement ≥30 µg/min, or norepinephrine-equivalent vasopressor dose, despite appropriate resuscitation, or ongoing escalation of vasopressor support at the time of enrollment.
8. Pregnancy (positive urine/serum hCG at screening or known pregnancy) or breastfeeding.
9. Uncontrolled ileus or gastrointestinal condition, such as an upper gastrointestinal bleed, preventing enteral dosing.
10. ADH/ALDH inhibitors (e.g., fomepizole, disulfiram) use in the prior 7 days or planned.
11. Severe dementia or neurodegenerative disease, defined as either impairment that prevents the patient from living independently at baseline or IQCODE >4.5. This exclusion also pertains to mental illnesses requiring long-term institutionalization, acquired or congenital intellectual disability, severe neuromuscular disorders, Parkinson's disease, and Huntington's disease. It also excludes patients with severe deficits due to structural brain diseases such as stroke, intracranial hemorrhage, cranial trauma, malignancy, anoxic brain injury, or cerebral edema.
12. Benzodiazepine dependency or alcohol dependency based on the medical team's decision to institute a specific treatment plan involving benzodiazepines or barbiturates (either as continuous infusions or intermittent intravenous boluses) for this dependency.
13. Active seizures during this ICU admission being treated with intravenous benzodiazepines.
14. Expected death within 24 hours of enrollment or lack of commitment to aggressive treatment by family/medical team (e.g., likely to withdraw life support measures within 24 hours of screening).
15. Admission to ICU only for post-operative monitoring or frequent neurologic assessments.
16. Incarcerated status.
17. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Attending physician refusal.
18. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient and/or surrogate refusal.
19. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient unable to consent and no surrogate available.
20. Current enrollment in a study that does not allow co-enrollment.

Study Design

Enrollment

40 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Ketone monoester

placebo comparator: Placebo

Interventions

Ketone monoester

Ketone 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

Placebo 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.

Primary outcome measure

  • Mean composite Confusion Assessment Method for the Intensive Care Unit-7 (CAM-ICU-7) delirium severity score [ Time Frame: From enrollment through study day 7. ]

Central Contacts and Locations

Central contacts

Locations

Vanderbilt University Medical Center

Recruiting

Nashville, Tennessee, United States, 37232

Contacts

More Information

Sponsor

Vanderbilt University Medical Center

Last update posted

Aug 24, 2026

Last verified

Aug, 2026

Keywords

  • ICU
  • Intensive Care Unit
  • Critical care
  • Critical illness
  • Ketones

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Vanderbilt University Medical Center on 2026-08-24.