Clinical trial NCT06535815: KetoNiFast: Cyclic Enteral Daytime Feeding With Ketogenic Nighttime Fasting
Official title: KetoNiFast: Impact of Cyclic Enteral Daytime Feeding With Ketogenic Nighttime Fasting on Outcome of Critical Ill Patients.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Nutrition
Muscle Loss
Inflammatory Response
Keywords: Ketogenic diet
ketogenic fasting
cyclic enteral nutrition
Lead sponsor: University Hospital of Cologne
Sponsor class: OTHER
First posted: 2024-08-02
Enrollment: 130
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Monocentric, prospective, randomized, interventional trial
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Loss of muscle mass
timeFrame: From date of randomization until the date of ICU discharge up to 1 month
measure: Progress of urea / creatinine ratio
timeFrame: From date of randomization until the date of ICU discharge up to 1 month
Secondary outcomes:
measure: Length of invasive and noninvasive ventilation
timeFrame: From date of randomization until the date of ICU discharge up to 1 month
measure: Length of ICU and hospital stay
timeFrame: From date of randomization until the date of hospital discharge up to 6 months
measure: 30 day mortality on day 30
timeFrame: From date of randomization 30 days
measure: ICU mobility scale on discharge
timeFrame: From date of randomization until the date of ICU discharge up to 1 month
Other outcomes:
Locations:
city: Cologne
country: Germany
facility: Department of Anesthesiology and Intensive Care Medicine
state: NRW
Study officials:
affiliation: University Hospital Cologne
name: Bernd W Böttiger, Prof
role: STUDY_DIRECTOR
References: