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

NCT ID: NCT06318299

Last Updated: 2025-08-28

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-06-20
• Study Completion Date: 2025-03-18

Brief Summary

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

Conditions

Ketosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: SINGLE

Study Groups

Ketone 1 hour

Ketone ester drink administered one hour before elective lumbar puncture

Group Type: ACTIVE_COMPARATOR

Ketone Ester

Intervention Type: DIETARY_SUPPLEMENT

Commercially available ketone ester drink (KetoneAid, Virginia, USA)

Ketone 2 hours

Ketone ester drink administered two hours before elective lumbar puncture

Group Type: ACTIVE_COMPARATOR

Ketone Ester

Intervention Type: DIETARY_SUPPLEMENT

Commercially available ketone ester drink (KetoneAid, Virginia, USA)

Placebo 1 hour

Placebo drink administered one hour before elective lumbar puncture

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Taste and appearance matched noncaloric placebo drink

Interventions

Ketone Ester

Commercially available ketone ester drink (KetoneAid, Virginia, USA)

Intervention Type: DIETARY_SUPPLEMENT

Placebo

Taste and appearance matched noncaloric placebo drink

Intervention Type: OTHER

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Aarhus University Hospital

OTHER

Sponsor Role: collaborator

University of Aarhus

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Niels Møller, Professor

Role: STUDY_DIRECTOR

Aarhus University Hospital

Locations

Aarhus University Hospital

Aarhus, , Denmark

Countries

Denmark

Other Identifiers

109227

Identifier Type: -

Identifier Source: org_study_id