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

Type 1 Diabetes Mellitus Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04656236
• Other study ID #: 1-10-72-251-20
• Status: Completed
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: March 1, 2022

Study information

• Verified date: December 2021
• Source: University of Aarhus
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 1, 2022
• Est. primary completion date: March 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 60 Years

Eligibility

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).

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 1
• Diabetic Ketoacidosis
• Ketosis
• Type 1 Diabetes Mellitus

Intervention

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

Locations

Country	Name	City	State
Denmark	Steno diabetes center Aarhus	Aarhus

Sponsors (2)

Lead Sponsor	Collaborator
University of Aarhus	Aarhus University Hospital

Country where clinical trial is conducted

Denmark, 

Outcome

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