Ketone Esters in T2DM

NCT04854330 | Unknown

• 1 other identifier: 007
• Study Type: interventional
• Target: 16
• Locations: 0 countries
• Sites: N/A

Brief Summary

Type 2 diabetes mellitus (T2DM) reduces the ability of the body to use sugar as a fuel. As an alternative people with T2DM can use fat from the blood stream instead. Fat is a good store of energy, however, the body requires about 20% more oxygen to produce energy from fat compared to sugar. People with T2DM often have heart disease as well. This can lead to limited availability of oxygen in the heart muscle, which increases the workload of the heart and will impact on the ability to perform everyday tasks, such as walking up a flight of steps. Recently, it has been suggested that ketone esters (a sports drink that contains ketones) may be used as an alternative source of energy for people with diabetes as they are approximately 8% more efficient than fat. The investigators will assess whether these ketones can be used as a more efficient source of energy and improve how the heart works in people with T2DM. If successful, this is a relatively cheap treatment, which could be immediately implemented in people with T2DM to improve heart function and the ability to perform everyday tasks.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Cardiac output

  Using thoracic impedance cardiography (Q-Link PhysioFlow, Manatec Ltd, Poissy, France), we will non-invasively measure stroke volume (ml/m2) and HR (b/min) to calculate cardiac output (L/min) at rest and during exercise.

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

Secondary Outcomes (8)

• Fuel utilisation test

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

• Exercise capacity and fuel utilisation during exercise test

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

• Near infrared spectrometry (NIRS)

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

• Ketone concentration

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

• Troponin concentration

  Crossover design. Assessed once on placebo and Ketone esters ~7 days apart

Study Arms (2)

Ketone ester

ACTIVE COMPARATOR

A Kme commercially available supplement will be given to the participants in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ΔG®; TΔS Ltd, UK, Oxford, UK; 0.30 ml.kg-1 body mass) and will be ingested with water and cherry-flavoured stevia in a total volume of 100 ml. Immediately following ingestion of the ketones, participants will be given 20 ml of calorie-free sparkling spring water (The Holywell Water Company Ltd, UK) in an attempt to remove any remaining flavour of the supplement.

Dietary Supplement: Ketone monoesters

Placebo

PLACEBO COMPARATOR

In the placebo condition, participants will consume 100 ml of water and cherry-flavoured stevia followed by the same 20 ml calorie-free sparkling spring water.

Dietary Supplement: Placebo

Interventions

Ketone monoesters DIETARY_SUPPLEMENT

A Kme commercially available supplement will be given to the participants in the form of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (ΔG®; TΔS Ltd, UK, Oxford, UK; 0.30 ml.kg-1 body mass) and will be ingested with water and cherry-flavoured stevia in a total volume of 100 ml.

Ketone ester

Placebo DIETARY_SUPPLEMENT

In the placebo condition, participants will consume 100 ml of water and cherry-flavoured stevia followed by the same 20 ml calorie-free sparkling spring water.

Placebo

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HbA1c \> 48 mmol/mol

You may not qualify if:

• they present with severe renal impairment (eGFR \< 30ml/min)
• they use concomitantly GLP-1 Receptor agonists (which reduce glucagon and therefore hydroxybutyrate production);
• they currently participating in a very low calorie diet or restricted carbohydrate diet (which artificially increase endogenous ketone production);
• they present uncontrolled hypertension (systolic blood pressure \> 180 mmHg);
• they have a history of myocardial infarction or cerebro-vascular events in the last 3 months;
• have a a BMI \> 40 kg/m2;
• they are unable to exercise;
• they have an allergy or intolerance to ketone esters ;
• they are unable to give informed consent
• have any other serious medical condition which in the opinion of study investigators would interfere with safety or data interpretation.

Sponsors & Collaborators

• University of Portsmouth: lead
• Portsmouth Hospitals NHS Trust: collaborator

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Central Study Contacts

Maria Perissiou, PhD

CONTACT

+447762860432; maria.perissiou@port.ac.uk

Anthony Shepherd, PhD

CONTACT

ant.shepherd@port.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Independent technician
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Lecturer in Physical Activity, Exercise and Health

Model Details: The proposed study design will be a randomised placebo-controlled, double-blind, crossover study.

Study Record Dates

• First Submitted: April 13, 2021
• First Posted: April 22, 2021
• Study Start: April 26, 2021
• Primary Completion: February 21, 2023
• Study Completion: February 21, 2023
• Last Updated: April 22, 2021

Record last verified: 2021-04