Pre-meals of 3-hydroxybutyrate in Type 2 Diabetes (PreKetone)
Primary Purpose
Ketosis, Postprandial Hyperglycemia, Glucose Metabolism Disorders (Including Diabetes Mellitus)
Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
3-hydroxybutyrate (3-OHB)
Sponsored by
About this trial
This is an interventional treatment trial for Ketosis
Eligibility Criteria
Inclusion Criteria:
- Older than 18 years of age
- Type 2 diabetes diagnosis
- No antiglycemic treatment or monotherapy with metformin
Exclusion Criteria:
- Hba1c > 70
- Severe liver disease (Child-Pugh score >10) or kidney disease (eGFR< 40 ml/min)
- Anemia (Hgb < 6.5 mM)
- History with pancreatitis
- Practicing ketogenic diets (i.e., low-carb diet, fasting regime)
- Inability to understand Danish or English
- Ongoing cancer or other acute/chronic serious diseases (PI will determine)
Sites / Locations
- Department of Endocrinology and Internal MedicineRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm 6
Arm Type
Placebo Comparator
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
0 gram 3-OHB 30 minutes before an OGTT
10 gram 3-OHB 30 minutes before an OGTT
20 gram 3-OHB 30 minutes before an OGTT
40 gram 3-OHB 30 minutes before an OGTT
20 gram 3-OHB 0 minutes before an OGTT
20 gram 3-OHB 60 minutes before an OGTT
Arm Description
0 gram 3-OHB 30 minutes before an OGTT
10 gram 3-OHB 30 minutes before an OGTT
20 gram 3-OHB 30 minutes before an OGTT
40 gram 3-OHB 30 minutes before an OGTT
20 gram 3-OHB 0 minutes before an OGTT
20 gram 3-OHB 60 minutes before an OGTT
Outcomes
Primary Outcome Measures
Blood glucose following the OGTT
Change in blood glucose following the OGTT and compared between the different visits. Incremental change (delta) from baseline to peak. Measured with laboratory kits.
Secondary Outcome Measures
Plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), acetaminophen, free fatty acids along others.
Incremental change (delta) from baseline to peak in plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1) following the OGGT and compared between the different visits. Measured with laboratory kits.
Full Information
NCT ID
NCT05581043
First Posted
October 4, 2022
Last Updated
February 27, 2023
Sponsor
University of Aarhus
Collaborators
Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
1. Study Identification
Unique Protocol Identification Number
NCT05581043
Brief Title
Pre-meals of 3-hydroxybutyrate in Type 2 Diabetes
Acronym
PreKetone
Official Title
Pre-meals of 3-hydroxybutyrate for People With Type 2 Diabetes
Study Type
Interventional
2. Study Status
Record Verification Date
October 2022
Overall Recruitment Status
Recruiting
Study Start Date
January 12, 2023 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
June 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Aarhus
Collaborators
Steno Diabetes Center Aarhus, Aarhus University Hospital, Denmark, Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Denmark
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem. Recently, our group found that oral consumption of the ketone metabolite, 3-hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastric emptying.The aim of this study is to investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes)
Detailed Description
Hyperglycemia following meals in patients with type 2 diabetes mellitus (T2DM) is a common problem, which can cause discomfort and fatigue but may also lead to diabetic complications. Small servings of macronutrients, especially protein-rich products, before a main meal (= pre-meals) has been shown to significantly lower postprandial glucose excursions in both healthy individuals and patients with T2DM. The reductions are primarily attributed the fact that protein stimulates insulin secretion and delays gastric emptying. The timing and dose of a premeal are essential for the glycemic reductions following a meal 4. Unfortunately, it often requires a rather large amount of protein (> 50 g) to facilitate clinically relevant reductions in postprandial glucose levels and a large protein intake may be unwanted for some patients (i.e., chronic kidney disease). Recently, our group found that oral consumption of the ketone metabolite, 3- hydroxybutyrate (3-OHB), effectively stimulates insulin secretion and delays gastricemptying. We have also shown that 3-OHB inhibits gluconeogenesis 6, which may further contribute to glucose-lowering effects. Two other clinical studies have shown that serving 3- OHB before an oral glucose tolerance test (OGTT) lowered glucose excursions in healthy volunteers and persons with impaired glucose tolerance. There are no current data available about the effect of 3-OHB premeals in T2DM patients, but we have preliminary data from an ongoing trial showing that 30 g of 3-OHB served 40 min before a mixed meal test effectively lowers postprandial glucose levels (around 3 mM) in patients with T2DM. The optimal dose and timing of 3-OHB pre-meals is unknown but important before initiating long-term clinical trials. We hypothesize that pre-melas of 3-OHB will affect postprandialglucose excursions in a time-dependent matter and servings 30 minutes before an OGTT is Deleted: 4 optimal in order to lower postprandial glucose excursions. The aim of this study is therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 20 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes). The primary endpoint is glucose trajectories following the OGTT. This study will give important insight into the optimal dose and timing for potential future clinical long-term studies in patients with metabolic diseases (i.e., T2DM, obesity)
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ketosis, Postprandial Hyperglycemia, Glucose Metabolism Disorders (Including Diabetes Mellitus)
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
We will use a randomized cross-over design to investigate 10 volunteers with T2DM on six different occasions separated with at least one week.
Masking
Participant
Allocation
Randomized
Enrollment
10 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
0 gram 3-OHB 30 minutes before an OGTT
Arm Type
Placebo Comparator
Arm Description
0 gram 3-OHB 30 minutes before an OGTT
Arm Title
10 gram 3-OHB 30 minutes before an OGTT
Arm Type
Experimental
Arm Description
10 gram 3-OHB 30 minutes before an OGTT
Arm Title
20 gram 3-OHB 30 minutes before an OGTT
Arm Type
Experimental
Arm Description
20 gram 3-OHB 30 minutes before an OGTT
Arm Title
40 gram 3-OHB 30 minutes before an OGTT
Arm Type
Experimental
Arm Description
40 gram 3-OHB 30 minutes before an OGTT
Arm Title
20 gram 3-OHB 0 minutes before an OGTT
Arm Type
Experimental
Arm Description
20 gram 3-OHB 0 minutes before an OGTT
Arm Title
20 gram 3-OHB 60 minutes before an OGTT
Arm Type
Experimental
Arm Description
20 gram 3-OHB 60 minutes before an OGTT
Intervention Type
Dietary Supplement
Intervention Name(s)
3-hydroxybutyrate (3-OHB)
Intervention Description
The aim of this study was therefore to i) investigate the dose/response relationship between 3-OHB servings of 0, 10, 20 and 40 grams 30 minutes before an OGTT and, ii) investigate the role of timing by serving 25 grams of 3-OHB at different timepoints ahead of an OGTT (0, 30 and 60 minutes).
Primary Outcome Measure Information:
Title
Blood glucose following the OGTT
Description
Change in blood glucose following the OGTT and compared between the different visits. Incremental change (delta) from baseline to peak. Measured with laboratory kits.
Time Frame
Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
Secondary Outcome Measure Information:
Title
Plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), acetaminophen, free fatty acids along others.
Description
Incremental change (delta) from baseline to peak in plasma concentrations of 3-OHB, insulin, C-peptide, glucagon like peptide-1 (GLP-1) following the OGGT and compared between the different visits. Measured with laboratory kits.
Time Frame
Blood samples will be obtained -60, -30, -15, 0, 15, 30, 45, 60, 90, 120, 150, 180 minutes from the OGTT
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Older than 18 years of age
Type 2 diabetes diagnosis
No antiglycemic treatment or monotherapy with metformin
Exclusion Criteria:
Hba1c > 70
Severe liver disease (Child-Pugh score >10) or kidney disease (eGFR< 40 ml/min)
Anemia (Hgb < 6.5 mM)
History with pancreatitis
Practicing ketogenic diets (i.e., low-carb diet, fasting regime)
Inability to understand Danish or English
Ongoing cancer or other acute/chronic serious diseases (PI will determine)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mads Bisgaard Bengtsen, MD, PhD
Phone
004529277453
Email
madsbengtsen@clin.au.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Nikolaj Rittig, MD, PhD
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Niels Møller, Professor
Organizational Affiliation
Professor
Official's Role
Study Director
Facility Information:
Facility Name
Department of Endocrinology and Internal Medicine
City
Aarhus
ZIP/Postal Code
8200
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Niels Møller, Professor
Phone
004578450000
12. IPD Sharing Statement
Learn more about this trial
Pre-meals of 3-hydroxybutyrate in Type 2 Diabetes
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