Metabolic Effects of Exogenous 3-hydroxybutyrate in Patients With Type 1 Diabetes and Healthy Controls

• Sponsor: University of Aarhus (Other)
• Overall Status: Completed
• CT.gov ID: NCT04656236
• Collaborator: Aarhus University Hospital (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Actual Duration (Months): 13.9
• Patients Per Site Per Month: 1.4

Study Details

Study Description

Brief Summary

The main objective of this clinical trial is to study the metabolic effects of intravenous infusion of the ketone body, 3-hydroxybutyrate (3-OHB), in patients with type 1 diabetes and healthy control subjects. Moreover, the investigators plan to examine regulatory mechanisms of 3-OHB that may be related to diabetic ketoacidosis.

The hypotheses are:

1. 3-OHB related inhibition of lipolysis is impaired in patients with type 1 diabetes.

2. Intravenous infusion of 3-OHB affects signaling pathways involved in the metabolic regulation in patients with type 1 diabetes and healthy controls.

3. 3-OHB infusion improves cardiac function in patients with type 1 diabetes and healthy controls.

The effects of 3-OHB will be investigated by isotopic tracers examinations, fat and muscle biopsies and blood samples. To evaluate effects on cardiac function echocardiography will be performed.

Condition or Disease	Intervention/Treatment	Phase
Type 1 Diabetes Mellitus; Diabetic Ketoacidosis	Biological: 3-hydroxybutyrate	N/A

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Intervention Model Description: Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.
• Masking: Single (Participant)
• Primary Purpose: Basic Science
• Official Title: Metabolic Effects of Exogenous 3-hydroxybutyrate in Patients With Type 1 Diabetes and Healthy Controls
• Actual Study Start Date: Jan 1, 2021
• Actual Primary Completion Date: Mar 1, 2022
• Actual Study Completion Date: Mar 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intervention 3 hours of continuously intravenous infusion of 3-hydroxybutyrate.	Biological: 3-hydroxybutyrate; 3-hydroxybutyrate is a metabolite, produced in the human body.
Placebo Comparator: Control 3 hours of continuously intravenous infusion of saline (NaCl).	Biological: 3-hydroxybutyrate; 3-hydroxybutyrate is a metabolite, produced in the human body.

Outcome Measures

Primary Outcome Measures

1. Differences in lipolysis rate [After 3 hours of interventions]

   Measured as differences in palmitate flux

Secondary Outcome Measures

1. Changes in protein metabolism [After 3 hours of interventions]

   Measured as differences in forearm and whole body tracer kinetics

2. Changes in glucose kinetics [After 3 hours of interventions]

   Measured by glucose tracer.

3. Cardiac function [After 2-3 hours of interventions]

   Changes in cardiac output and left ventricular ejection fraction measured by echocardiography

4. Changes in signaling in muscle and adipose tissue [After 1,5-3 hours of interventions]

   Western blot examinations of muscle and adipose tissue biopsies

5. Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide [During the 3 hours intervention period]

   Blood samples

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 60 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: Yes

Patients with type 1 diabetes:

Inclusion Criteria:

• Type 1 diabetes diagnosis

• C-peptide negative

• 19 < BMI < 26

• written consent

Exclusion Criteria:

• Severe comorbidity

• Regular medication apart from insulin (except over-the-counter medicines)

• Use of long acting insulin analogues, that work > 24 hours, e.g. Tresiba

• PI finds the patient not fit (e.g. mental illness, too nervous, unacceptable screening blood tests or other).

Healthy control subjects:

Inclusion Criteria:

• 19 < BMI < 26

• written consent

Exclusion Criteria:

• Chronic disease

• Regular medication (except over-the-counter medicines)

• PI finds the patient not fit (e.g. mental illness, too nervous, unacceptable screening blood tests or other).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Steno diabetes center Aarhus	Aarhus		Denmark	8000

Sponsors and Collaborators

• University of Aarhus
• Aarhus University Hospital

Investigators

• Study Director: Niels Møller, Professor, Department of Endocrinology and Steno Diabetes Center Aarhus, Aarhus University Hospital
• Principal Investigator: Maj Bangshaab, MD, Steno Diabetes Center Aarhus and Aarhus University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Aarhus
• ClinicalTrials.gov Identifier: NCT04656236
• Other Study ID Numbers: 1-10-72-251-20
• First Posted: Dec 7, 2020
• Last Update Posted: Mar 8, 2022
• Last Verified: Dec 1, 2021

• 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 1; Ketosis; Diabetic Ketoacidosis

Study Results

No Results Posted as of Mar 8, 2022