Clinical trial NCT03935841: Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).
Official title: Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Incretin Effect
Ketosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
First posted: 2019-05-02
Enrollment: 8
Sex: MALE
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions:

1. blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
2. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption.

The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously.

Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

Detailed description: An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions with at least 48 hours apart.

1. blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
2. blood sampling while given a variable rate of 3-OHB salt intravenously to replicate the concentrations seen during oral consumption.

The primary outcome is differences in insulin concentrations (incremental AUC) 180 minutes after 3-OHB consumed orally vs. intravenously.

Secondary outcomes includes iAUC for other gastrointestinal hormones and substrates (Glucagon, GLP-1, GIP, glucose, and 3-OHB) Gastric emptying will be evaluated using 1500 mg Paracetamol consumption before each intervention day. Urine will be analyzed for ketone concentrations/excretion rates.

Eligibility criteria: Inclusion Criteria:

* healthy
* 19\<BMI\<30
* written og oral consent
* No allergies to paracetamol

Exclusion Criteria:

* Chronic disease or daily medical treatment
* Daily intake of ketones or ketogenic diets
* Speaks and understands Danish
* Screening blood sample abnormalities

Primary outcomes:
measure: plasma insulin
timeFrame: 180 minutes
Secondary outcomes:
measure: Plasma Glucagon
timeFrame: 180 minutes
measure: Gastric emptying
timeFrame: 180 minutes
measure: Urine 3-OHB
timeFrame: 180 minutes
measure: Plasma GLP1
timeFrame: 180 minutes
measure: Plasma GIP
timeFrame: 180 minutes
measure: Plasma glucose
timeFrame: 180 minutes
measure: Plasma free fatty acids
timeFrame: 180 minutes
measure: Plasma 3-OHB
timeFrame: 180 minutes
measure: Plasma Ghrelin
timeFrame: 180 minutes
measure: Plasma PYY
timeFrame: 180 minutes
measure: height
timeFrame: at time 0 minutes
measure: weight
timeFrame: at time 0 minutes
measure: BMI
timeFrame: time 0 minutes
measure: Blood pressure
timeFrame: time 0 minutes and 180 minutes
measure: Satiety questionnaire (Blundell et al. 2010)
timeFrame: At 0, 60, 120, and 180 minutes
measure: Ad libitum food intake
timeFrame: at time = 180 minutes
Other outcomes:
Locations:
city: Aarhus N
country: Denmark
facility: Department of Diabetes and Hormone Diseases (DoH)
Study officials:
affiliation: Aarhus University Hospital
name: Niels Jessen, Professor
role: STUDY_DIRECTOR
References:
citation: Rittig N, Svart M, Thomsen HH, Vestergaard ET, Rehfeld JF, Hartmann B, Holst JJ, Johannsen M, Moller N, Jessen N. Oral D/L-3-Hydroxybutyrate Stimulates Cholecystokinin and Insulin Secretion and Slows Gastric Emptying in Healthy Males. J Clin Endocrinol Metab. 2020 Oct 1;105(10):dgaa483. doi: 10.1210/clinem/dgaa483.