Exogenous Ketones in People With Type 1 Diabetes

August 30, 2023 updated by: Insel Gruppe AG, University Hospital Bern

A Single-centre, Randomised, Single-blinded Crossover Study Evaluating the Metabolic Effects of a Ketone Ester Food Supplement in People With Type 1 Diabetes

The aim of this pilot study is to investigate the metabolic effects of exogenous ketone ester food supplements, by assessing the change in blood acid-base balance, and the level of blood beta-hydroxy-butyrate in people with type 1 diabetes during resting conditions.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

The ketone bodies acetoacetate, β-hydroxybutyrate (βHB) and acetone are small lipid-derived molecules that are produced in the liver under certain conditions such as starvation, very low carbohydrate intake and prolonged glycogen-depleting exercise. Ketone bodies serve as an alternative energy substrate for the brain and other metabolically active tissues under periods of low glucose availability, and can modulate carbohydrate and lipid metabolism. Previously, controlled physiological ketosis required a low carbohydrate diet, starvation or administration of acetoacetate (AcAc) salts which were all unpleasant or potentially harmful. The development of ketone esters provides an alternative method to increase βHB levels, and has been shown to be well tolerated in rodents and humans. Two examples are the R,S-1,3-butanediol acetoacetate diester and the (R)-3-hydroxybutyl (R)-3-hydroxybutyrate ketone monoester. Ingestion of either have been shown to result in short-term (0.5-6 hours) nutritional ketosis (βHB >1mM). Nutritional ketosis can therefore be achieved without the need for the impracticality of ketogenic dieting or fasting.

In recent years there has been considerable interest in ketone body food supplements due to their potential for improved exercise performance and therapeutic glucose lowering effects in people with type 2 diabetes. Exogenous ketone supplements may be of particular interest for individuals living with type 1 diabetes by serving as an alternative fuel substrate to reduce the reliance on glucose utilisation and spare endogenous glycogen and reduce the risk of hypoglycaemia in certain situations, such as exercise. Stubbs et al. (2017) found that drinks containing exogenous ketones were a practical and efficacious way to raise blood βHB levels with only a modest change in acid-base balance in healthy individuals without diabetes (after 60 min, blood pH declined from 7.41 to 7.31 following a ketone ester drink). To date, no studies have investigated the metabolic effects of ketone in people with type 1 diabetes.

Study Type

Interventional

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Switzerland
      • Bern, Switzerland, 3010
        • University of Bern

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years to 41 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • Type 1 diabetes for >1 year
  • Male and female aged 18-45 years old
  • HbA1c <8.5% (69 mmol/mol) based on analysis from the central laboratory unit of Bern University Hospital
  • Using either continuous subcutaneous insulin infusion or multiple daily injections
  • Wearing a continuous glucose monitor (CGM) or flash glucose monitor (fGM)
  • Written informed consent

Exclusion Criteria:

  • Physical or psychological disease likely to interfere with the normal conduct of the study and interpretation of the results as judged by the investigator
  • Current treatment with drugs known to interfere with metabolism e.g. systemic corticosteroids, statins, SGLT2 inhibitors, GLP1 agonists
  • Relevant diabetic complications as judged by the investigator
  • Body mass index > 30 kg/m2
  • Uncontrolled hypertension (>180/100 mmHg)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Low-dose KE
141 mg/kg bodyweight of ketone esters
Dietary supplement: Ketone ester supplement
Participants taking part in this study will receive a drink containing either 141 or 282 mg/kg bodyweight of ketone esters in a randomised order. These doses are in line with recommendations by the company HVMN from which the supplements for this study will be obtained.
Other Names:
  • H.V.M.N Ketone Ester food supplement
Experimental: High-dose KE
282 mg/kg bodyweight of ketone esters
Dietary supplement: Ketone ester supplement
Participants taking part in this study will receive a drink containing either 141 or 282 mg/kg bodyweight of ketone esters in a randomised order. These doses are in line with recommendations by the company HVMN from which the supplements for this study will be obtained.
Other Names:
  • H.V.M.N Ketone Ester food supplement

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in venous blood pH
Time Frame: Over a 3 hour period from baseline following ingestion of a ketone ester drink in people with type 1 diabetes.
Change in blood pH over a 3 hour period from baseline following ingestion of a ketone ester drink
Over a 3 hour period from baseline following ingestion of a ketone ester drink in people with type 1 diabetes.

Secondary Outcome Measures

Outcome Measure
Time Frame
Blood total ketone level /beta hydroxy butyrate level
Time Frame: 3 hours
3 hours
Blood glucose concentration
Time Frame: 3 hours
3 hours
Substrate oxidation rates determined using indirect calorimetry, via RER (respiratory exchange ratio)
Time Frame: 3 hours
3 hours
Gastro-intestinal distress symptoms via a questionnaire
Time Frame: 3 hours
3 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Insel Gruppe AG, University Hospital Bern

Investigators

  • Principal Investigator: Christoph Stettler, MD, University of Bern

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

August 1, 2023

Primary Completion (Estimated)

November 1, 2023

Study Completion (Estimated)

December 1, 2023

Study Registration Dates

First Submitted

July 22, 2020

First Submitted That Met QC Criteria

July 22, 2020

First Posted (Actual)

July 27, 2020

Study Record Updates

Last Update Posted (Actual)

September 1, 2023

Last Update Submitted That Met QC Criteria

August 30, 2023

Last Verified

August 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • KEsupplements

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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