Effects of Exogenous Ketone Ester Supplementation on 3-hydroxybutyrate Concentrations in Human Cerebrospinal Fluid (KetoBrain)

It is well established that the brain is capable of consuming ketone bodies, especially during low glucose availability, e.g. fasting. Cerebral metabolism of ketone bodies depends on passage of the blood brain barrier and especially the global blood concentration of ketone bodies.

Ketone bodies can be administered exogenously, and the most commonly used in clinical trials is 3-hydroxybutyrate (3-OHB). 3-OHB is carried by simple diffusion and facilitated diffusion through several monocarboxylic acid transporters (MCTs) across the blood-brain barrier.

To our knowledge, no studies in human adults exist that concurrently measure 3-OHB concentrations in blood and cerebrospinal fluid (CSF) after ingestion or infusion of exogenous ketone supplementation, necessitating further study.

Aims:

• The 3-OHB CSF/blood ratio after oral ingestion of 30 g ketone ester - primary endpoint
• The window of effect: Ketone supplementation 1 h or 2 h before CSF sampling
• If concentration measurements by point-of-care testing are non-inferior to mass spectrometry
• If acute 3-OHB ingestion increases plasma brain-derived neurotrophic factor (BDNF) levels

Study Overview

• Status: Not yet recruiting
• Conditions: Ketosis
• Intervention / Treatment: Dietary supplement: Ketone Ester; Other: Placebo

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Simon Kjær Simonsen, MD; Phone Number: +45 28769491; Email: simkjr@clin.au.dk
• Study Contact Backup: Name: Mads Vandsted Svart, PhD; Phone Number: +45 28118221; Email: mvsv@clin.au.dk

Study Locations

• Denmark
  • Aarhus, Denmark, 8200
    • Aarhus University Hospital
    • Contact: Simon Kjær Simonsen, MD; Phone Number: +45 28769491; Email: simkjr@clin.au.dk
    • Contact: Mads Vandsted Svart, PhD; Phone Number: +45 28118221; Email: mvsv@clin.au.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• All sexes
• Referred to undergo an elective lumbar puncture procedure in the outpatient clinic at Department of Neurology, Aarhus University Hospital.
• Age 18-80 years
• Written and oral consent

Exclusion Criteria:

• Referred to the clinic suspecting severe neuroinflammation
• Special diet habits, including ketogenic diet, fasting, intermittent fasting etc.
• Daily use of insulin or other medication affecting blood glucose and/or glucose metabolism
• Not able to speak or understand Danish and/or give written and oral consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Ketone 1 hour; Ketone ester drink administered one hour before elective lumbar puncture	Dietary supplement: Ketone Ester; Commercially available ketone ester drink (KetoneAid, Virginia, USA)
Active Comparator: Ketone 2 hours; Ketone ester drink administered two hours before elective lumbar puncture	Dietary supplement: Ketone Ester; Commercially available ketone ester drink (KetoneAid, Virginia, USA)
Placebo Comparator: Placebo 1 hour; Placebo drink administered one hour before elective lumbar puncture	Other: Placebo; Taste and appearance matched noncaloric placebo drink

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
3-OHB CSF/blood ratio	After oral ingestion of 30 g ketone ester drink or placebo drink	1-2 hours after ingestion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF 3-OHB concentrations, POCT	After oral ingestion of 30 g ketone ester drink or placebo drink, Point-of-care testing (POCT)	1-2 hours after ingestion
CSF 3-OHB concentrations, Mass Spectrometry	After oral ingestion of 30 g ketone ester drink or placebo drink, Mass Spectrometry Detection	1-2 hours after ingestion
CSF glucose concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink	1-2 hours after ingestion
Blood 3-OHB concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink, Point-of-care testing (POCT)	1-2 hours after ingestion
Plasma 3-OHB concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink, Mass Spectrometry Detection	1-2 hours after ingestion
Blood glucose concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink, Point-of-care testing (POCT)	1-2 hours after ingestion
Plasma BDNF concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink	1-2 hours after ingestion
Blood 3-OHB concentrations	Before oral ingestion of 30 g ketone ester drink or placebo drink, Point-of-care testing (POCT)	Before ingestion
Plasma 3-OHB concentrations	After oral ingestion of 30 g ketone ester drink or placebo drink, Mass Spectrometry Detection	Before ingestion
Blood glucose concentrations	Before oral ingestion of 30 g ketone ester drink or placebo drink, Point-of-care testing (POCT)	Before ingestion
Plasma BDNF concentrations	Before oral ingestion of 30 g ketone ester drink or placebo drink	Before ingestion

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: Aarhus University Hospital
• Investigators: Study Director: Niels Møller, Professor, Aarhus University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2024
• Primary Completion (Estimated): December 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: March 12, 2024
• First Submitted That Met QC Criteria: March 12, 2024
• First Posted (Actual): March 19, 2024

Study Record Updates

• Last Update Posted (Actual): March 21, 2024
• Last Update Submitted That Met QC Criteria: March 19, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Point-of-Care Testing; Brain-Derived Neurotrophic Factor; Cerebrospinal Fluid; Ketone Bodies; Ketone body adminstration
• Additional Relevant MeSH Terms: Metabolic Diseases; Acid-Base Imbalance; Acidosis; Ketosis
• Other Study ID Numbers: 109227

Drug and device information, study documents

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