Exogenous Ketones in People With Type 1 Diabetes

NCT ID: NCT04487678

Last Updated: 2023-09-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

WITHDRAWN

Clinical Phase

NA

Study Classification

INTERVENTIONAL

Study Start Date

2023-08-31

Study Completion Date

2023-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Ketosis, Diabetic

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Single-centre, randomised, single blinded, crossover study in 6 individuals with type 1 diabetes (see inclusion/exclusion criteria)
Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Participants
There will be two intervention arms that will take place in a randomised, single blinded fashion so that participants are not aware of which dose of ketone esters they receive

Study Groups

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Low-dose KE

141 mg/kg bodyweight of ketone esters

Group Type EXPERIMENTAL

Ketone ester supplement

Intervention Type DIETARY_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.

High-dose KE

282 mg/kg bodyweight of ketone esters

Group Type EXPERIMENTAL

Ketone ester supplement

Intervention Type DIETARY_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.

Interventions

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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.

Intervention Type DIETARY_SUPPLEMENT

Other Intervention Names

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H.V.M.N Ketone Ester food supplement

Eligibility Criteria

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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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

Yes

Sponsors

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Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Christoph Stettler, MD

Role: PRINCIPAL_INVESTIGATOR

University of Bern

References

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Balasse EO, Fery F. Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev. 1989 May;5(3):247-70. doi: 10.1002/dmr.5610050304.

Reference Type BACKGROUND
PMID: 2656155 (View on PubMed)

Clarke K, Tchabanenko K, Pawlosky R, Carter E, Todd King M, Musa-Veloso K, Ho M, Roberts A, Robertson J, Vanitallie TB, Veech RL. Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate in healthy adult subjects. Regul Toxicol Pharmacol. 2012 Aug;63(3):401-8. doi: 10.1016/j.yrtph.2012.04.008. Epub 2012 May 3.

Reference Type BACKGROUND
PMID: 22561291 (View on PubMed)

Cox PJ, Clarke K. Acute nutritional ketosis: implications for exercise performance and metabolism. Extrem Physiol Med. 2014 Oct 29;3:17. doi: 10.1186/2046-7648-3-17. eCollection 2014.

Reference Type BACKGROUND
PMID: 25379174 (View on PubMed)

Cox PJ, Kirk T, Ashmore T, Willerton K, Evans R, Smith A, Murray AJ, Stubbs B, West J, McLure SW, King MT, Dodd MS, Holloway C, Neubauer S, Drawer S, Veech RL, Griffin JL, Clarke K. Nutritional Ketosis Alters Fuel Preference and Thereby Endurance Performance in Athletes. Cell Metab. 2016 Aug 9;24(2):256-68. doi: 10.1016/j.cmet.2016.07.010. Epub 2016 Jul 27.

Reference Type BACKGROUND
PMID: 27475046 (View on PubMed)

Egan B. The glucose-lowering effects of exogenous ketones: is there therapeutic potential? J Physiol. 2018 Apr 15;596(8):1317-1318. doi: 10.1113/JP275938. Epub 2018 Mar 24. No abstract available.

Reference Type BACKGROUND
PMID: 29473164 (View on PubMed)

Egan B, D'Agostino DP. Fueling Performance: Ketones Enter the Mix. Cell Metab. 2016 Sep 13;24(3):373-375. doi: 10.1016/j.cmet.2016.08.021.

Reference Type BACKGROUND
PMID: 27626197 (View on PubMed)

Evans M, Cogan KE, Egan B. Metabolism of ketone bodies during exercise and training: physiological basis for exogenous supplementation. J Physiol. 2017 May 1;595(9):2857-2871. doi: 10.1113/JP273185. Epub 2016 Dec 7.

Reference Type BACKGROUND
PMID: 27861911 (View on PubMed)

Flint A, Raben A, Blundell JE, Astrup A. Reproducibility, power and validity of visual analogue scales in assessment of appetite sensations in single test meal studies. Int J Obes Relat Metab Disord. 2000 Jan;24(1):38-48. doi: 10.1038/sj.ijo.0801083.

Reference Type BACKGROUND
PMID: 10702749 (View on PubMed)

Kesl SL, Poff AM, Ward NP, Fiorelli TN, Ari C, Van Putten AJ, Sherwood JW, Arnold P, D'Agostino DP. Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and lipoprotein levels in Sprague-Dawley rats. Nutr Metab (Lond). 2016 Feb 4;13:9. doi: 10.1186/s12986-016-0069-y. eCollection 2016.

Reference Type BACKGROUND
PMID: 26855664 (View on PubMed)

Myette-Cote E, Neudorf H, Rafiei H, Clarke K, Little JP. Prior ingestion of exogenous ketone monoester attenuates the glycaemic response to an oral glucose tolerance test in healthy young individuals. J Physiol. 2018 Apr 15;596(8):1385-1395. doi: 10.1113/JP275709. Epub 2018 Mar 2.

Reference Type BACKGROUND
PMID: 29446830 (View on PubMed)

Pinckaers PJ, Churchward-Venne TA, Bailey D, van Loon LJ. Ketone Bodies and Exercise Performance: The Next Magic Bullet or Merely Hype? Sports Med. 2017 Mar;47(3):383-391. doi: 10.1007/s40279-016-0577-y.

Reference Type BACKGROUND
PMID: 27430501 (View on PubMed)

Robinson AM, Williamson DH. Physiological roles of ketone bodies as substrates and signals in mammalian tissues. Physiol Rev. 1980 Jan;60(1):143-87. doi: 10.1152/physrev.1980.60.1.143. No abstract available.

Reference Type BACKGROUND
PMID: 6986618 (View on PubMed)

Stubbs BJ, Cox PJ, Evans RD, Santer P, Miller JJ, Faull OK, Magor-Elliott S, Hiyama S, Stirling M, Clarke K. On the Metabolism of Exogenous Ketones in Humans. Front Physiol. 2017 Oct 30;8:848. doi: 10.3389/fphys.2017.00848. eCollection 2017.

Reference Type BACKGROUND
PMID: 29163194 (View on PubMed)

Other Identifiers

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KEsupplements

Identifier Type: -

Identifier Source: org_study_id

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