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

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.

Study Overview

• Status: Completed
• Conditions: Type 1 Diabetes Mellitus; Diabetic Ketoacidosis
• Intervention / Treatment: Biological: 3-hydroxybutyrate

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aarhus, Denmark, 8000
    • Steno Diabetes Center Aarhus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences in lipolysis rate	Measured as differences in palmitate flux	After 3 hours of interventions

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in protein metabolism	Measured as differences in forearm and whole body tracer kinetics	After 3 hours of interventions
Changes in glucose kinetics	Measured by glucose tracer.	After 3 hours of interventions
Cardiac function	Changes in cardiac output and left ventricular ejection fraction measured by echocardiography	After 2-3 hours of interventions
Changes in signaling in muscle and adipose tissue	Western blot examinations of muscle and adipose tissue biopsies	After 1,5-3 hours of interventions
Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide	Blood samples	During the 3 hours intervention period

Collaborators and Investigators

• Sponsor: University of Aarhus
• Collaborators: 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 record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2021
• Primary Completion (ACTUAL): March 1, 2022
• Study Completion (ACTUAL): March 1, 2022

Study Registration Dates

• First Submitted: November 30, 2020
• First Submitted That Met QC Criteria: November 30, 2020
• First Posted (ACTUAL): December 7, 2020

Study Record Updates

• Last Update Posted (ACTUAL): March 8, 2022
• Last Update Submitted That Met QC Criteria: March 7, 2022
• Last Verified: December 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Endocrine System Diseases; Diabetes Complications; Acid-Base Imbalance; Acidosis; Diabetes Mellitus; Diabetes Mellitus, Type 1; Ketosis; Diabetic Ketoacidosis
• Other Study ID Numbers: 1-10-72-251-20

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No