Exogenous Ketones in Type 2 Diabetes

• Sponsor: University of British Columbia (Other)
• Overall Status: Completed
• CT.gov ID: NCT04194450
• Collaborator: (none)
• Enrollment: 18
• Location: 1
• Arms: 2
• Actual Duration (Months): 28.1
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Ketosis; Type 2 Diabetes	Dietary Supplement: Ketone monoester; Dietary Supplement: Placebo	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 18 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Placebo masked with flavouring and participants consume in opaque containers.
• Primary Purpose: Basic Science
• Official Title: The Effect of Acute Exogenous Oral Ketone Supplementation on Blood Glucose Levels in Type 2 Diabetes
• Actual Study Start Date: Jan 15, 2020
• Actual Primary Completion Date: May 20, 2022
• Actual Study Completion Date: May 20, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketone monoester Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight)	Dietary Supplement: Ketone monoester; Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.
Placebo Comparator: Placebo Acute dose of flavour-matched placebo.	Dietary Supplement: Placebo; Acute ingestion of taste-matched placebo prior to assessment of outcomes.

Outcome Measures

Primary Outcome Measures

1. Plasma glucose [180 minutes]

   Plasma glucose concentration after ketone or placebo ingestion

Secondary Outcome Measures

1. Plasma insulin [180 minutes]

   Insulin across concentration after ketone or placebo ingestion

2. Plasma C-peptide [180 minutes]

   C-peptide across concentration after ketone or placebo ingestion

3. Plasma free fatty acids [180 minutes]

   Non-esterified fatty acid concentration after ketone or placebo ingestion

4. Plasma tumour necrosis factor alpha [180 minutes]

   Plasma tumour necrosis factor alpha concentration after ketone or placebo ingestion

5. Plasma tumour interleukin-1beta [180 minutes]

   Plasma tumour interleukin-1beta concentration after ketone or placebo ingestion

6. Plasma tumour interleukin-6 [180 minutes]

   Plasma tumour interleukin-6 concentration after ketone or placebo ingestion

7. Cerebral blood flow [180 minutes]

   Intracranial blood flow velocity measured by ultrasound

8. Blood pressure [180 minutes]

   Blood pressure measured manually and by Finipres

9. Cognitive function [180 minutes]

   Measures of cognitive function using Brain Baseline battery on an iPad.

10. Brain-derived neurotrophic factor [180 minutes]

    Brain-derived neurotrophic factor concentrations after ketone or placebo ingestion

11. Blood monocytes [180 minutes]

    Total blood monocytes and monocyte subsets after ketone or placebo ingestion

12. Self reported hunger and fullness [180 minutes]

    Self reported hunger and fullness by a 0 to 100 mm Visual Analog Scale (higher scores mean greater hunger or fullness)

13. Gastrointestinal symptoms [180 minutes]

    Gastroinestinal symptom questionnaire scores after ketone or placebo ingestion on a 0 to 100 mm Visual Analog Scale (higher scores mean greater symptoms)

14. Total energy consumed [180 minutes after ketone or placebo ingestion]

    Total energy consumed in kilocalories in buffet style meal after ketone or placebo ingestion

15. Monocyte histone acetylation [180 minutes]

    Histone acetylation status of monocytes measured after ketone or placebo ingestion

Eligibility Criteria

Criteria

• Ages Eligible for Study: 20 Years to 69 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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

• 20-75 years old

Exclusion Criteria:

• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of British Columbia, Okanagan	Kelowna	British Columbia	Canada	V1V 1V7

Sponsors and Collaborators

• University of British Columbia

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Jonathan Little, Assistant Professor, University of British Columbia
• ClinicalTrials.gov Identifier: NCT04194450
• Other Study ID Numbers: H19-02947
• First Posted: Dec 11, 2019
• Last Update Posted: Aug 2, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Diabetes Mellitus; Diabetes Mellitus, Type 2

Study Results

No Results Posted as of Aug 2, 2022