Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).
Primary Purpose
Healthy, Incretin Effect, Ketosis
Status
Completed
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
3-OHB salt (NaCl)
Sponsored by
About this trial
This is an interventional basic science trial for Healthy
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
Sites / Locations
- Department of Diabetes and Hormone Diseases (DoH)
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
3-OHB orally
3-OHB intravenously
Arm Description
36 gram 3-OHB salt consumed orally
Variable amounts of 3-OHB salt given i order to replicate the same individual plasma concentrations measured during the experimental arm.
Outcomes
Primary Outcome Measures
plasma insulin
incremental area under the curve (iAUC) for plasma insulin concentrations {pmol/l}
Secondary Outcome Measures
Plasma Glucagon
iAUC and concentrations of (Glucagon {pg/ml}
Gastric emptying
Paracetamol test, 1500 mg following interventions and measuring plasma paracetamol {micromol/l}
Urine 3-OHB
Excretion rates {gram/hour} will be estimated as = urine output {L} x urine 3-OHB concentration {mmol/l} x 0.1041 {g/mmol}/180 minutes
Plasma GLP1
iAUC and concentrations of GLP-1 {pmol/l},
Plasma GIP
iAUC and concentrations of GIP {pmol/l},
Plasma glucose
iAUC and concentrations of glucose {mmol/l},
Plasma free fatty acids
iAUC and concentrations of free fatty acids {mmol/l},
Plasma 3-OHB
iAUC and concentrations of 3-OHB {mmol/l})
Plasma Ghrelin
iAUC and concentrations of Ghrelin {ng/l})
Plasma PYY
iAUC and concentrations of PYY {pg/ml})
height
height {meters}
weight
weight {kg}
BMI
Body mass index = weight/height^2
Blood pressure
Arm blood pressure
Satiety questionnaire (Blundell et al. 2010)
VAS/NRS-score of hunger, fullness, satiety, desire, and prospective consumption
Ad libitum food intake
gram (and kcal) intake of an ad libitum meal (sandwich)
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT03935841
Brief Title
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
2. Study Status
Record Verification Date
November 2020
Overall Recruitment Status
Completed
Study Start Date
June 7, 2019 (Actual)
Primary Completion Date
November 1, 2019 (Actual)
Study Completion Date
March 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Aarhus
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An open-labeled intervention study testing healthy, lean, and male volunteers on two separate occasions:
blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
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.
blood sampling after consuming 36 gram 3-Hydroxybutyrate (3-OHB) salt.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Healthy, Incretin Effect, Ketosis
7. Study Design
Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
8 (Actual)
8. Arms, Groups, and Interventions
Arm Title
3-OHB orally
Arm Type
Experimental
Arm Description
36 gram 3-OHB salt consumed orally
Arm Title
3-OHB intravenously
Arm Type
Active Comparator
Arm Description
Variable amounts of 3-OHB salt given i order to replicate the same individual plasma concentrations measured during the experimental arm.
Intervention Type
Dietary Supplement
Intervention Name(s)
3-OHB salt (NaCl)
Intervention Description
36 gram 3-OHB salt diluted in 500 ml sterile water
Primary Outcome Measure Information:
Title
plasma insulin
Description
incremental area under the curve (iAUC) for plasma insulin concentrations {pmol/l}
Time Frame
180 minutes
Secondary Outcome Measure Information:
Title
Plasma Glucagon
Description
iAUC and concentrations of (Glucagon {pg/ml}
Time Frame
180 minutes
Title
Gastric emptying
Description
Paracetamol test, 1500 mg following interventions and measuring plasma paracetamol {micromol/l}
Time Frame
180 minutes
Title
Urine 3-OHB
Description
Excretion rates {gram/hour} will be estimated as = urine output {L} x urine 3-OHB concentration {mmol/l} x 0.1041 {g/mmol}/180 minutes
Time Frame
180 minutes
Title
Plasma GLP1
Description
iAUC and concentrations of GLP-1 {pmol/l},
Time Frame
180 minutes
Title
Plasma GIP
Description
iAUC and concentrations of GIP {pmol/l},
Time Frame
180 minutes
Title
Plasma glucose
Description
iAUC and concentrations of glucose {mmol/l},
Time Frame
180 minutes
Title
Plasma free fatty acids
Description
iAUC and concentrations of free fatty acids {mmol/l},
Time Frame
180 minutes
Title
Plasma 3-OHB
Description
iAUC and concentrations of 3-OHB {mmol/l})
Time Frame
180 minutes
Title
Plasma Ghrelin
Description
iAUC and concentrations of Ghrelin {ng/l})
Time Frame
180 minutes
Title
Plasma PYY
Description
iAUC and concentrations of PYY {pg/ml})
Time Frame
180 minutes
Title
height
Description
height {meters}
Time Frame
at time 0 minutes
Title
weight
Description
weight {kg}
Time Frame
at time 0 minutes
Title
BMI
Description
Body mass index = weight/height^2
Time Frame
time 0 minutes
Title
Blood pressure
Description
Arm blood pressure
Time Frame
time 0 minutes and 180 minutes
Title
Satiety questionnaire (Blundell et al. 2010)
Description
VAS/NRS-score of hunger, fullness, satiety, desire, and prospective consumption
Time Frame
At 0, 60, 120, and 180 minutes
Title
Ad libitum food intake
Description
gram (and kcal) intake of an ad libitum meal (sandwich)
Time Frame
at time = 180 minutes
10. Eligibility
Sex
Male
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Niels Jessen, Professor
Organizational Affiliation
Aarhus University Hospital
Official's Role
Study Director
Facility Information:
Facility Name
Department of Diabetes and Hormone Diseases (DoH)
City
Aarhus N
ZIP/Postal Code
8200
Country
Denmark
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
32717058
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.
Results Reference
derived
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Metabolic Differences of an Oral and Intravenous Dose of 3-hydroxybutyrate (3-OHB).
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