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

Primary Purpose

Type 1 Diabetes Mellitus, Diabetic Ketoacidosis

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

3-hydroxybutyrate

About this trial

This is an interventional basic science trial for Type 1 Diabetes Mellitus

Eligibility Criteria

18 Years - 60 Years (Adult)MaleAccepts Healthy Volunteers

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).

Sites / Locations

Steno diabetes center Aarhus

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Intervention

Control

Arm Description

3 hours of continuously intravenous infusion of 3-hydroxybutyrate.

3 hours of continuously intravenous infusion of saline (NaCl).

Outcomes

Primary Outcome Measures

Differences in lipolysis rate

Measured as differences in palmitate flux

Secondary Outcome Measures

Changes in protein metabolism

Measured as differences in forearm and whole body tracer kinetics

Changes in glucose kinetics

Measured by glucose tracer.

Cardiac function

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

Changes in signaling in muscle and adipose tissue

Western blot examinations of muscle and adipose tissue biopsies

Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide

Blood samples

Full Information

NCT ID

NCT04656236

First Posted

November 30, 2020

Last Updated

March 7, 2022

Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital

1. Study Identification

Unique Protocol Identification Number

NCT04656236

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2021

Overall Recruitment Status

Completed

Study Start Date

January 1, 2021 (Actual)

Primary Completion Date

March 1, 2022 (Actual)

Study Completion Date

March 1, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Aarhus

Collaborators

Aarhus University Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. 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: 3-OHB related inhibition of lipolysis is impaired in patients with type 1 diabetes. Intravenous infusion of 3-OHB affects signaling pathways involved in the metabolic regulation in patients with type 1 diabetes and healthy controls. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Type 1 Diabetes Mellitus, Diabetic Ketoacidosis

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Model Description

Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.

Masking

Participant

Allocation

Randomized

Enrollment

20 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Intervention

Arm Type

Experimental

Arm Description

3 hours of continuously intravenous infusion of 3-hydroxybutyrate.

Arm Title

Control

Arm Type

Placebo Comparator

Arm Description

3 hours of continuously intravenous infusion of saline (NaCl).

Intervention Type

Biological

Intervention Name(s)

3-hydroxybutyrate

Intervention Description

3-hydroxybutyrate is a metabolite, produced in the human body.

Primary Outcome Measure Information:

Title

Differences in lipolysis rate

Description

Measured as differences in palmitate flux

Time Frame

After 3 hours of interventions

Secondary Outcome Measure Information:

Title

Changes in protein metabolism

Description

Measured as differences in forearm and whole body tracer kinetics

Time Frame

After 3 hours of interventions

Title

Changes in glucose kinetics

Description

Measured by glucose tracer.

Time Frame

After 3 hours of interventions

Title

Cardiac function

Description

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

Time Frame

After 2-3 hours of interventions

Title

Changes in signaling in muscle and adipose tissue

Description

Western blot examinations of muscle and adipose tissue biopsies

Time Frame

After 1,5-3 hours of interventions

Title

Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide

Description

Blood samples

Time Frame

During the 3 hours intervention period

10. Eligibility

Sex

Male

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

60 Years

Accepts Healthy Volunteers

Eligibility Criteria

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).

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Niels Møller, Professor

Organizational Affiliation

Department of Endocrinology and Steno Diabetes Center Aarhus, Aarhus University Hospital

Official's Role

Study Director

First Name & Middle Initial & Last Name & Degree

Maj Bangshaab, MD

Organizational Affiliation

Steno Diabetes Center Aarhus and Aarhus University

Official's Role

Principal Investigator

Facility Information:

Facility Name

Steno diabetes center Aarhus

City

Aarhus

ZIP/Postal Code

8000

Country

Denmark

12. IPD Sharing Statement

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

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