KetoNiFast: Cyclic Enteral Daytime Feeding With Ketogenic Nighttime Fasting (KetoNiFast)

KetoNiFast: Impact of Cyclic Enteral Daytime Feeding With Ketogenic Nighttime Fasting on Outcome of Critical Ill Patients.

A physiological human nutrition includes circadian feeding and nighttime fasting during sleep. There is increasing evidence, that this natural fasting episode over nighttime majorly contributes to repair processes of the human body. So far, intensive care patients are normally enterally fed continuously, so that there is no circadian nutrition and no nighttime fasting. An enteral nutrition for 12 hours followed by a fasting period of 12 hours supported by exogenous ketone salts potentially improves the reconstitution of ICU patients compared to ICU patients who are continuously enterally fed.

Study Overview

• Status: Recruiting
• Conditions: Inflammatory Response; Muscle Loss; Nutrition
• Intervention / Treatment: Other: Cyclic enteral feeding with nighttime fasting and exogenous ketone salt supplementation (ß-hydroxybutyrate)

Detailed Description

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. 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. A cyclic enteral nutrition with 12 hours of daytime feeding and 12 hours of ketogenic nighttime fasting compared to a continuous enteral feeding for 24 hours can potentially improve the reconstitution of critically ill Intensive Care patients. This improved reconstitution can be measured by maintenance of muscle mass (measured by ultrasound of the musculus rectus femoris), urea/creatinine ration, length of ventilation, length of ICU and hospital stay, 30-day mortality, ICU mobility scale.

• Study Type: Interventional
• Enrollment (Estimated): 130
• 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

Study Locations

• Germany
  • NRW
    • Cologne, NRW, Germany, 50937
      • Recruiting
      • Department of Anesthesiology and Intensive Care Medicine
      • Contact: Sandra E Stoll, MD; Phone Number: +491735697566; Email: sandraemilystoll@googlemail.com
      • Contact: Sandra E Stoll, MD; Phone Number: Stoll +491735697566; Email: sandra-emily.stoll@gmx.de
      • Principal Investigator: Sandra E Stoll, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• written informed consent to participate in this study
• admission to ICU
• enteral nutrition

Exclusion Criteria:

• Severe liver dysfunction / liver failure (Child Pugh >7 points / category B)
• Severe kidney dysfunction (KDIGO stage 3)
• Total pancreatectomy / insulin dependent diabetes mellitus (IDDM)
• Pregnancy / lactation
• Hemoglobin concentration < 80g/l
• Severe metabolic disorders / severe autoimmune diseases
• Refractory metabolic or respiratory acidosis
• Dysfunction of mitochondrial transport of fatty acids
• Dysfunction of oxidation of fatty acids
• Dysfunction of gluconeogenesis, production and reduction of ketones
• Intermittent Porphyria
• Severe cardiac arrhythmias / cardiomyopathy
• Contraindication against enteral nutrition
• Lack of 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
Active Comparator: Interventional: Cyclic enteral nutrition with ketogenic nighttime fasting; Interventional group: 12 hours of enteral feeding (as per patients´individual calorimetric requirements measured by indirect calorimetry) followed by a fasting period of 12 hours supported by the supplementation of exogenous ketone salts.	Other: Cyclic enteral feeding with nighttime fasting and exogenous ketone salt supplementation (ß-hydroxybutyrate); 12 hours of enteral feeding (as per patients´individual calorimetric requirements measured by indirect calorimetry) followed by a fasting period of 12 hours supported by the supplementation of exogenous ketone salts.; Other Names: cyclic nutrition with nighttime fasting and exogenous ß-hydroxybutyrate supplementation
No Intervention: Control: Conventional continuous enteral nutrition; Control group Continuous enteral nutrition for 24 hours (as per patients´ individual caloric requirements defined by indirect calorimetry).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Loss of muscle mass	Loss of muscle mass via Ultrasound of M. rectus femoris of a predefined leg	From date of randomization until the date of ICU discharge up to 1 month
Progress of urea / creatinine ratio	Urea / creatinine ratio in the patients´ blood	From date of randomization until the date of ICU discharge up to 1 month

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of invasive and noninvasive ventilation	Length of invasive and noninvasive ventilation	From date of randomization until the date of ICU discharge up to 1 month
Length of ICU and hospital stay	Length of ICU and hospital stay	From date of randomization until the date of hospital discharge up to 6 months
30 day mortality on day 30	30 day mortality on day 30	From date of randomization 30 days
ICU mobility scale on discharge	ICU mobility scale (lowest score 0, highest score 10)	From date of randomization until the date of ICU discharge up to 1 month

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 (Actual): September 1, 2023
• Primary Completion (Estimated): December 31, 2025
• Study Completion (Estimated): March 1, 2026

Study Registration Dates

• First Submitted: July 23, 2024
• First Submitted That Met QC Criteria: July 30, 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; ketogenic fasting; cyclic enteral nutrition
• Other Study ID Numbers: 22-1398_1

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