Clinical trial NCT04656236: 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
Overall status: COMPLETED
Phase: NA
Conditions: Type 1 Diabetes Mellitus
Diabetic Ketoacidosis
Lead sponsor: University of Aarhus
Sponsor class: OTHER
Collaborators: name: Aarhus University Hospital
First posted: 2020-12-07
Enrollment: 20
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Crossover design in 2 different groups, patients with type 1 diabetes and healthy controls.
Primary purpose: BASIC_SCIENCE

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.


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).

Primary outcomes:
measure: Differences in lipolysis rate
timeFrame: After 3 hours of interventions
Secondary outcomes:
measure: Changes in protein metabolism
timeFrame: After 3 hours of interventions
measure: Changes in glucose kinetics
timeFrame: After 3 hours of interventions
measure: Cardiac function
timeFrame: After 2-3 hours of interventions
measure: Changes in signaling in muscle and adipose tissue
timeFrame: After 1,5-3 hours of interventions
measure: Differences in circulating concentrations of 3-hydroxybutyrate, glucose, free fatty acids, insulin, glucagon and C-peptide
timeFrame: During the 3 hours intervention period
Other outcomes:
Locations:
city: Aarhus
country: Denmark
facility: Steno diabetes center Aarhus
Study officials:
affiliation: Department of Endocrinology and Steno Diabetes Center Aarhus, Aarhus University Hospital
name: Niels Møller, Professor
role: STUDY_DIRECTOR
affiliation: Steno Diabetes Center Aarhus and Aarhus University
name: Maj Bangshaab, MD
role: PRINCIPAL_INVESTIGATOR
References: