Exogenous Ketone Ester Supplementation in ICU Delirium (KETONES ICU)

Plain English Summary

Exogenous Ketone Supplementation in ICU Delirium is a Phase 1 clinical trial sponsored by Vanderbilt University Medical Center studying ICU Delirium, Critical Illness. This study will test if a special ketone drink is safe and easy to give to patients in the intensive care unit (ICU). It is for adult patients in the ICU who are experiencing or at risk of delirium, which is a state of confusion. Participants will receive either the ketone supplement or a placebo drink through a feeding tube or by mouth, and will be monitored for up to 7 days. Currently, there are no specific treatments to prevent or treat delirium in the ICU, making this research important. The trial aims to enroll 40 participants.

Official 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.

Who Can Participate

Here is what you need to know about eligibility for this trial. Adults (18+) admitted to the medical ICU who are expected to stay for at least 24 hours. Patients who can receive liquid medication by mouth or through a feeding tube. Patients must not have severe metabolic acidosis, diabetic ketoacidosis, very low blood sugar, or certain other serious health conditions. Individuals with severe dementia, certain neurological diseases, or those who are pregnant will not be eligible. This trial is studying ICU Delirium, Critical Illness, so participants generally need a confirmed diagnosis.

What They're Measuring

The study will measure how well patients can tolerate the ketone supplement and if it can be safely given, looking for early signs that it might reduce confusion or shorten the time patients experienc The specific primary outcome measures are: Feasibility: Proportion of participants achieving target peak serum β-hydroxybutyrate (1.5-3.5 mmol/L) on at least 50% of dosing days (From enrollment through study day 7 or ICU discharge.); Safety and tolerability: Number of participants with ≥1 prespecified safety or tolerability event (From enrollment through study day 7.). These endpoints are how researchers determine whether the treatment is effective and will form the basis of any future regulatory submissions.

About This Phase

This trial is in Phase 1, the first major stage of clinical testing. Phase 1 trials typically involve 20-100 participants and focus on safety, dosage levels, and side effects. The primary goal is not to test whether the treatment works but to establish that it is safe enough for further testing. About 70% of Phase 1 drugs advance to Phase 2. If successful, the treatment will proceed to Phase 2 efficacy testing.

Why This Trial Matters

This trial addresses the significant problem of ICU delirium, a common and serious condition that leads to worse long-term outcomes for patients, by investigating a novel supplement that may help redu This research targets ICU Delirium, Critical Illness, where improved treatment options are needed.

Investor Insight

This Phase 1 trial is an early-stage investigation into a novel therapeutic approach for ICU delirium, a condition with significant unmet medical needs, suggesting potential for future market entry if Phase 1 trials have approximately a 10% chance of eventually gaining FDA approval.

Is This Trial Right for Me?

Ask your doctor if this study is right for you and what the potential benefits and risks are. If you join, you will receive either the ketone drink or a placebo, and your condition will be closely monitored by the medical team. The study involves regular assessments for delirium and blood tests to check ketone levels. The trial is being conducted at 1 site. Always discuss clinical trial participation with your healthcare provider before making any decisions. This information is for educational purposes only and is not medical advice.

AI-generated analysis for educational purposes only. This is not medical advice. Discuss clinical trial participation with your doctor. Data sourced from ClinicalTrials.gov.

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: QUADRUPLE
• Enrollment: 40 participants

Interventions

• DRUG: 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).
• DRUG: 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 Outcomes

• Feasibility: Proportion of participants achieving target peak serum β-hydroxybutyrate (1.5-3.5 mmol/L) on at least 50% of dosing days (From enrollment through study day 7 or ICU discharge.)
• Safety and tolerability: Number of participants with ≥1 prespecified safety or tolerability event (From enrollment through study day 7.)

Secondary Outcomes

• Feasibility: Proportion of scheduled post-dose serum β-hydroxybutyrate draws completed (From enrollment through study day 7 or ICU discharge.)
• Feasibility: Proportion of post-dose serum β-hydroxybutyrate measurements >4.0 mmol/L (From enrollment through study day 7 or ICU discharge.)
• Feasibility: Adherence to ketone dose-titration algorithm (From enrollment through study day 7 or ICU discharge.)
• Delirium- and coma-free days (DCFDs) through study day 7 (From enrollment through study day 7.)
• Delirium severity score on the Confusion Assessment Method for the Intensive Care Unit-7 (CAM-ICU-7) scale (From enrollment through study day 7.)

Full Eligibility Criteria

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 AST/ALT \> 5× ULN or total bilirubin \> 3 mg/dL.
7. Refractory shock (defined as norepinephrine dose ≥20 µg/min or use of a second vasopressor agent).
8. Pregnancy (positive urine/serum hCG at screening or known pregnancy).
9. Uncontrolled ileus or gastrointestinal condition, such as an upper gastrointestinal bleed, preventing enteral dosing.
10. SGLT2 inhibitor use within the prior 7 days.
11. ADH/ALDH inhibitors (e.g., fomepizole, disulfiram) use in the prior 7 days or planned.
12. Severe dementia or neurodegenerative disease, defined as either impairment that prevents the patient from living independently at baseline or IQCODE \>4.5, measured using a patient's qualified surrogate. 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.
13. 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.
14. Active seizures during this ICU admission being treated with intravenous benzodiazepines.
15. 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).
16. Admission to ICU only for post-operative monitoring or frequent neurologic assessments.
17. Incarcerated status.
18. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Attending physician refusal.
19. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient and/or surrogate refusal.
20. Inability to obtain informed consent within 24 hours from the time all inclusion criteria were met: Patient unable to consent and no surrogate available.
21. Current enrollment in a study that does not allow co-enrollment.

Trial Locations

• Vanderbilt University Medical Center, Nashville, Tennessee, United States

Frequently Asked Questions

Related Conditions

• ICU Delirium
• Critical Illness
• Cognitive Impairment
• Post-Traumatic Stress Disorder (PTSD)
• Dementia
• Metabolic Acidosis
• Diabetic Ketoacidosis
• Hepatic Failure
• Shock
• Neurodegenerative Diseases

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