DeliKet (Substudy of KetoNiFast Study ID 22-1398_1) (DeliKet)

Impact of Cyclic, Daytime Enteral Nutrition and Ketogenic Nighttime Fasting on the Incidence of Postoperative Delirium in Critically Ill Patients

Postoperative delirium is a common problem of the critically ill patient and associated with an increased mortality. Intermittent fasting and ketogenesis have been shown to be beneficial for maintaining a circadian rhythm and initiating anti-inflammatory repair mechanisms which could potentially be neuroprotective. However, so far there is little data if cyclic enteral feeding with ketogenic nighttime fasting might be beneficial for reducing the rate of postoperative delirium. The study hypothesis is that equicaloric cyclic enteral feeding (12 hrs) during daytime with ketogenic fasting and exogenous ketone supplementation at nighttime compared to continuous standard enteral nutrition (24 hours) decreases the incidence of postoperative delirium in critically ill patients.

Study Overview

• Status: Not yet recruiting
• Conditions: Delirium; Nutrition, Healthy; Ketogenic Dieting
• Intervention / Treatment: Dietary supplement: Cyclic enteral daytime feeding with ketogenic nighttime fasting and exogenous ketone salt supplementation (ß-hydroxybutyrate)

Detailed Description

Postoperative delirium remains a common postoperative problem in critically ill patients with a prevalence of up to 20% and even up to 50% in the elderly population. But postoperative delirium has a negative impact on mortality as several studies were able to show in the past. Therefore, aiming for a reduction of postoperative delirium has an important impact on patients' outcome. One helpful tool for avoiding postoperative delirium is maintaining a circadian pattern. Enteral feeding may play an important role here. Healthy humans have a circadian feeding pattern with nighttime fasting. There is increasing evidence that a circadian rhythm of feeding (cyclic feeding) could be beneficial for critical ill patients. Cyclic feeding and fasting are assumed to have positive effects on the gut microbiome resulting in optimization of host responses to gastrointestinal pathogens. Another positive effect of cyclic feeding potentially results from activation of a "fasting response", inducing repair pathways such as ketogenesis, mitochondrial biogenesis, anti-inflammatory pathways, antioxidant defenses and autophagy processes. The activation of these repair pathways could diminish cellular stress and promote cellular recovery in critical ill patients. This could have a positive effect on postoperative delirium. A randomized controlled trial by van Dyck et al. could show that fasting-mimicking intervals of 12 hours are sufficient to generate a metabolic fasting response without risking a caloric deficit. This fasting response can be enhanced by additional supplementation of exogenous ketones. The study objective is that equicaloric cyclic enteral feeding (for 12 hours) during daytime with ketogenic fasting (for 12 hours) at nighttime (aiming for a ß-hydroxybutyrate blood concentrations ≥ 0.5mM by exogenous ketone supplementation) compared to continuous (for 24 hours) standard enteral nutrition as per patients' nutritional requirements decreases the incidence of postoperative delirium of critically ill patients.

• Study Type: Interventional
• Enrollment (Estimated): 90
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sandra E Stoll, MD, assProf.; Phone Number: 82054 +49221478; Email: sandraemilystoll@googlemail.com
• Study Contact Backup: Name: Fabian Dusse, PD, MD; Phone Number: 40806 +49221478; Email: fabian.dusse@uk-koeln.de

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥ 18 years
• Admission to an ICU
• Start of enteral nutrition

Exclusion Criteria:

• Severe liver insufficiency / liver disease (Child Pugh > B or 7-9 points)
• Post total Pancreatectomy / Insulin-depending diabetes mellitus (IDDM)
• Pregnancy / Lactation
• Hemoglobin-concentration < 80g/l
• Severe metabolic disorder / severe autoimmune disease
• Refractory respiratory or metabolic acidosis
• Disorder of mitochondrial transportation of fatty acids
• Disorder of the oxidation of fatty acids
• Disorder of gluconeogenesis, der ketone body production or ketone body degradation
• Intermittent porphyria
• Severe arrhythmia / cardiomyopathy
• Contraindications against enteral nutrition
• Missing informed consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Interventional group: Cyclic enteral nutrition with ketogenic nighttime fasting; Interventional group: Cyclic enteral daytime nutrition (12 hours) with ketogenic nighttime fasting (12 hours) with supplementation of exogenous ketones (ß-hydroxybutyrate) in the Intensive Care Setting.	Dietary supplement: Cyclic enteral daytime feeding with ketogenic nighttime fasting and exogenous ketone salt supplementation (ß-hydroxybutyrate); Nighttime fasting and ß-hydroxybutyrate supplementation; Other Names: cyclic nutrition with nighttime fasting and exogenous ß-hydroxybutyrate supplementation
No Intervention: Control group: Conventional continuous enteral nutrition; Continuous (24 hours) enteral nutrition in the Intensive Care Setting.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confusion Assessment Method (CAM- ICU)	CAM ICU score (lowest score 0, highest score 7) • Cognitive function (MoCA- and MMST- Score) day 1, 7, 14 / ICU discharge	Day 1-14 after randomization or until ICU discharge
• Montreal Cognitive Assessment (MoCA- Score)	• Cognitive function (MoCA- Score) (lowest Score 0, highest Score 30)	Day 1-14 after randomization or until ICU- discharge
MMSE (Minimental State Examination)	MMSE Score (lowest Score 0, highest Score 30)	Day 1-14 after randomization or until ICU discharge

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration of ventilation	Length of invasive and noninvasive ventilation	From day of randomization until ICU discharge up to 1 month
Length of ICU- and Hospital stay	Length of ICU- and Hospital stay	From day of randomization until hospital discharge up to 6 months
30-day mortality	Mortality at day 30 after ICU admission	From day of randomization up until 30 days

Collaborators and Investigators

• Sponsor: University Hospital of Cologne
• Investigators: Study Director: Bernd W Böttiger, Prof, University Hospital Cologne

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2024
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: July 30, 2024
• First Submitted That Met QC Criteria: August 1, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Actual): August 6, 2024
• Last Update Submitted That Met QC Criteria: August 4, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: ketogenic diet; postoperative delirium; cyclic nutrition
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Confusion; Neurobehavioral Manifestations; Neurocognitive Disorders; Delirium
• Other Study ID Numbers: 22-1398_2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No