NCT04194450

Brief Summary

Exogenous ketone supplements are proposed to have glucose-lowering potential, provide an alternative fuel for the brain and to enhance cognitive function. No studies have tested whether exogenous ketones can lower blood glucose in people with type 2 diabetes. In addition, the impact of exogenous ketones on brain blood flow, cognitive function or brain-derived neurotrophic factor in humans is unknown. The purpose of this study is to determine if acutely ingesting exogenous ketones, in the form of a ketone monoester drink, can lower glucose and improve measures of brain/cognitive function in humans with type 2 diabetes. Participants will consume a ketone monoester drink or placebo with blood samples, brain blood flow, and cognitive function assessed over 180 minutes. The researchers will also test how the ketone monoester drink impacts appetite and measures of inflammation.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
19

participants targeted

Target at below P25 for not_applicable

Timeline
Completed

Started Jan 2020

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 9, 2019

Completed
2 days until next milestone

First Posted

Study publicly available on registry

December 11, 2019

Completed
1 month until next milestone

Study Start

First participant enrolled

January 15, 2020

Completed
2.3 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 20, 2022

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 20, 2022

Completed
1.6 years until next milestone

Results Posted

Study results publicly available

December 11, 2023

Completed
Last Updated

May 30, 2025

Status Verified

May 1, 2025

Enrollment Period

2.3 years

First QC Date

December 9, 2019

Results QC Date

March 14, 2023

Last Update Submit

May 28, 2025

Conditions

Outcome Measures

Primary Outcomes (1)

  • Plasma Glucose

    Plasma glucose concentration after ketone or placebo ingestion

    180 minutes

Secondary Outcomes (15)

  • Plasma Insulin

    180 minutes

  • Plasma C-peptide

    180 minutes

  • Plasma Free Fatty Acids

    180 minutes

  • Plasma Tumour Necrosis Factor Alpha

    180 minutes

  • Plasma Tumour Interleukin-1beta

    180 minutes

  • +10 more secondary outcomes

Study Arms (2)

Ketone monoester

EXPERIMENTAL

Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight)

Dietary Supplement: Ketone monoester

Placebo

PLACEBO COMPARATOR

Acute dose of flavour-matched placebo.

Dietary Supplement: Placebo

Interventions

Ketone monoesterDIETARY_SUPPLEMENT

Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.

Ketone monoester
PlaceboDIETARY_SUPPLEMENT

Acute ingestion of taste-matched placebo prior to assessment of outcomes.

Placebo

Eligibility Criteria

Age20 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • physician-diagnosed type 2 diabetes of ≥1 year
  • current hemoglobin A1C (HbA1c) of 6.5-8.0%
  • treatment with lifestyle or stable (≥3 months) oral glucose-lowering medications
  • blood pressure of \<160/99 mm Hg assessed according to guidelines
  • non-smoking
  • no prior history of cardiovascular disease or stroke
  • not on hormone replacement therapy, corticosteroids, or anti-inflammatory medications
  • years old

You may not qualify if:

  • being a competitive endurance athlete
  • taking exogenous insulin or sodium glucose transporter 2 (SGLT2) inhibitors
  • following a ketogenic diet, low-calorie diet, periodic fasting regimen, or consume ketogenic supplements
  • being unable to travel to and from the university
  • being unable to follow the controlled diet instructions
  • being pregnant or planning to become pregnant during the study (if female)
  • disorders of fat metabolism, chronic pancreatitis, had gastric bypass surgery and/or gallbladder disease
  • being unable to read or communicate in English

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of British Columbia, Okanagan

Kelowna, British Columbia, V1V 1V7, Canada

Location

Related Publications (1)

  • Baranowski BJ, Oliveira BF, Falkenhain K, Little JP, Mohammad A, Beaudette SM, Finch MS, Caldwell HG, Neudorf H, MacPherson REK, Walsh JJ. Effect of exogenous beta-hydroxybutyrate on BDNF signaling, cognition, and amyloid precursor protein processing in humans with T2D and insulin-resistant rodents. Am J Physiol Cell Physiol. 2025 Feb 1;328(2):C541-C556. doi: 10.1152/ajpcell.00867.2024. Epub 2025 Jan 13.

MeSH Terms

Conditions

KetosisDiabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

AcidosisAcid-Base ImbalanceMetabolic DiseasesNutritional and Metabolic DiseasesDiabetes MellitusGlucose Metabolism DisordersEndocrine System Diseases

Results Point of Contact

Title
Dr. Jonathan Little
Organization
University of British Columbia

Publication Agreements

PI is Sponsor Employee
Yes

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Masking Details
Placebo masked with flavouring and participants consume in opaque containers.
Purpose
BASIC SCIENCE
Intervention Model
CROSSOVER
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor

Study Record Dates

First Submitted

December 9, 2019

First Posted

December 11, 2019

Study Start

January 15, 2020

Primary Completion

May 20, 2022

Study Completion

May 20, 2022

Last Updated

May 30, 2025

Results First Posted

December 11, 2023

Record last verified: 2025-05

Data Sharing

IPD Sharing
Will not share

Locations