Trial Outcomes & Findings for Exogenous Ketones in Type 2 Diabetes (NCT NCT04194450)

NCT ID: NCT04194450

Last Updated: 2025-05-30

Results Overview

Plasma glucose concentration after ketone or placebo ingestion

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 19 participants
• Primary outcome timeframe: 180 minutes
• Results posted on: 2025-05-30

Participant Flow

Participant milestones

Measure	Placebo-Ketones Crossover design: Placebo - washout period of \>2days - Ketones	Ketones-Placebo Crossover design: Ketones - washout period of \>2days - Placebo.
Overall Study STARTED	9	10
Overall Study COMPLETED	8	10
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Measure	Placebo-Ketones Crossover design: Placebo - washout period of \>2days - Ketones	Ketones-Placebo Crossover design: Ketones - washout period of \>2days - Placebo.
Overall Study not eligible	1	0

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Overall n=18 Participants Total participants independent of crossover order (Placebo-Ketones and Ketones-Placebo).
Age, Continuous	62 years STANDARD_DEVIATION 8 • n=18 Participants
Sex: Female, Male Female	7 Participants n=18 Participants
Sex: Female, Male Male	11 Participants n=18 Participants
Region of Enrollment Canada	18 Participants n=18 Participants

PRIMARY outcome

Timeframe: 180 minutes

Plasma glucose concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Glucose Baseline	7.3 mmol/L Standard Deviation 1.8	7.2 mmol/L Standard Deviation 1.8
Plasma Glucose 30 minutes	6.2 mmol/L Standard Deviation 1.2	6.6 mmol/L Standard Deviation 1.9
Plasma Glucose 60 minutes	6.3 mmol/L Standard Deviation 1.5	6.2 mmol/L Standard Deviation 1.8
Plasma Glucose 90 minutes	6.2 mmol/L Standard Deviation 1.5	5.9 mmol/L Standard Deviation 1.2
Plasma Glucose 120 minutes	5.7 mmol/L Standard Deviation 1.5	6.2 mmol/L Standard Deviation 0.9
Plasma Glucose 150 minutes	5.7 mmol/L Standard Deviation 1.4	5.7 mmol/L Standard Deviation 1.1
Plasma Glucose 180 minutes	5.6 mmol/L Standard Deviation 1.4	6.4 mmol/L Standard Deviation 1.5

SECONDARY outcome

Timeframe: 180 minutes

Insulin across concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Insulin baseline	26.7 pg/mL Standard Deviation 17.4	28.2 pg/mL Standard Deviation 18.2
Plasma Insulin 180minutes	24.3 pg/mL Standard Deviation 17.2	21.4 pg/mL Standard Deviation 15.4

SECONDARY outcome

Timeframe: 180 minutes

C-peptide across concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma C-peptide baseline	4,384 pg/mL Standard Deviation 2,155	4,438 pg/mL Standard Deviation 2,241
Plasma C-peptide 180 minutes	3,908 pg/mL Standard Deviation 1,859	3,918 pg/mL Standard Deviation 2,232

SECONDARY outcome

Timeframe: 180 minutes

Non-esterified fatty acid concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Free Fatty Acids 180 minutes	0.18 mmol/L Standard Deviation 0.11	0.43 mmol/L Standard Deviation 0.16
Plasma Free Fatty Acids baseline	0.42 mmol/L Standard Deviation 0.14	0.40 mmol/L Standard Deviation 0.18

SECONDARY outcome

Timeframe: 180 minutes

Plasma tumour necrosis factor alpha concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Tumour Necrosis Factor Alpha baseline	1.1 pg/mL Standard Deviation 0.5	1.2 pg/mL Standard Deviation 0.4
Plasma Tumour Necrosis Factor Alpha 180min	1.0 pg/mL Standard Deviation 0.4	1.1 pg/mL Standard Deviation 0.4

SECONDARY outcome

Timeframe: 180 minutes

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

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Tumour Interleukin-1beta baseline	253 fg/mL Standard Deviation 450	115 fg/mL Standard Deviation 74
Plasma Tumour Interleukin-1beta 180min	106 fg/mL Standard Deviation 105	102 fg/mL Standard Deviation 41

SECONDARY outcome

Timeframe: 180 minutes

Plasma tumour interleukin-6 concentration after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Plasma Tumour Interleukin-6 baseline	1.5 pg/mL Standard Deviation 0.8	2.7 pg/mL Standard Deviation 1.6
Plasma Tumour Interleukin-6 180min	2.7 pg/mL Standard Deviation 1.6	2.7 pg/mL Standard Deviation 1.6

SECONDARY outcome

Timeframe: 180 minutes

Population: Procedure not completed due to the unavailability of a specialized research staff. Data was not and will not be obtained and reported.

Intracranial blood flow velocity measured by ultrasound

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 180 minutes

Blood pressure measured manually and by Finipres

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Blood Pressure Systolic blood pressure baseline	133 mmHg Standard Deviation 18	130 mmHg Standard Deviation 16
Blood Pressure Systolic blood pressure 180min	139 mmHg Standard Deviation 19	136 mmHg Standard Deviation 18
Blood Pressure Diastolic blood pressure baseline	79 mmHg Standard Deviation 7	77 mmHg Standard Deviation 10
Blood Pressure Diastolic blood pressure 180min	83 mmHg Standard Deviation 11	78 mmHg Standard Deviation 14

SECONDARY outcome

Timeframe: 180 minutes

Number of Correct Answers on the Digital Symbol Substitution Task. Measure of cognitive function using Brain Baseline battery on an iPad.

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Cognitive Function - Digital Symbol Substitution Task baseline Digit-symbol substitution task	32.8 number correct Standard Deviation 8.7	32.4 number correct Standard Deviation 8.2
Cognitive Function - Digital Symbol Substitution Task 180min Digit-symbol substitution task	35.7 number correct Standard Deviation 7.5	34.5 number correct Standard Deviation 6.9

SECONDARY outcome

Timeframe: 180 minutes

Brain-derived neurotrophic factor concentrations after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Brain-derived Neurotrophic Factor 180 minutes	4.8 ng/mL Standard Deviation 6.7	5.7 ng/mL Standard Deviation 9.0
Brain-derived Neurotrophic Factor baseline	7.1 ng/mL Standard Deviation 13.0	5.5 ng/mL Standard Deviation 8.1

SECONDARY outcome

Timeframe: 180 minutes

Total blood monocytes count (x10^3 cells/uL) after ketone or placebo ingestion

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Number Blood Monocytes (x10^3 Cells/uL) baseline Monocytes	408 x10^3 cells/uL Standard Deviation 171	442 x10^3 cells/uL Standard Deviation 152
Number Blood Monocytes (x10^3 Cells/uL) 180min Monocytes	445 x10^3 cells/uL Standard Deviation 181	447 x10^3 cells/uL Standard Deviation 179

SECONDARY outcome

Timeframe: 180 minutes

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

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Self Reported Hunger and Fullness baseline how hungry	46 mm Standard Deviation 26	42 mm Standard Deviation 31
Self Reported Hunger and Fullness 180 minutes how hungry	58 mm Standard Deviation 21	60 mm Standard Deviation 23

SECONDARY outcome

Timeframe: 180 minutes

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

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Gastrointestinal Symptoms belching	0 mm Interval 0.0 to 46.0	0 mm Interval 0.0 to 59.0
Gastrointestinal Symptoms cramping	0 mm Interval 0.0 to 12.0	0 mm Interval 0.0 to 22.0
Gastrointestinal Symptoms nausea	0 mm Interval 0.0 to 59.0	0 mm Interval 0.0 to 22.0
Gastrointestinal Symptoms urge to vomit	0 mm Interval 0.0 to 32.0	0 mm Interval 0.0 to 69.0
Gastrointestinal Symptoms bloating	0 mm Interval 0.0 to 42.0	0 mm Interval 0.0 to 24.0

SECONDARY outcome

Timeframe: 180 minutes after ketone or placebo ingestion

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

Outcome measures

Measure	Ketone Monoester n=18 Participants Acute dose of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (0.3 g/kg body weight) Ketone monoester: Acute ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate prior to assessment of outcomes.	Placebo n=18 Participants Acute dose of flavour-matched placebo. Placebo: Acute ingestion of taste-matched placebo prior to assessment of outcomes.
Total Energy Consumed	823 kcal Standard Deviation 377	948 kcal Standard Deviation 455

SECONDARY outcome

Timeframe: 180 minutes

Population: This assay was not performed due to insufficient sample quantity.

Histone acetylation status of monocytes measured after ketone or placebo ingestion

Outcome measures

Outcome data not reported

Adverse Events

Overall

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Jonathan Little

University of British Columbia

Phone: (250) 807-9876

Email: jonathan.little@ubc.ca

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place