Exogenous Ketones in People With Type 1 Diabetes

NCT04487678 | Withdrawn

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

Brief Summary

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.

Conditions

Ketosis, Diabetic

Outcome Measures

Primary Outcomes (1)

• Change in venous blood pH

  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 Outcomes (4)

• Blood total ketone level /beta hydroxy butyrate level

  3 hours

• Blood glucose concentration

  3 hours

• Substrate oxidation rates determined using indirect calorimetry, via RER (respiratory exchange ratio)

  3 hours

• Gastro-intestinal distress symptoms via a questionnaire

  3 hours

Study Arms (2)

Low-dose KE

EXPERIMENTAL

141 mg/kg bodyweight of ketone esters

Dietary Supplement: Ketone ester supplement

High-dose KE

EXPERIMENTAL

282 mg/kg bodyweight of ketone esters

Dietary Supplement: Ketone ester supplement

Interventions

Ketone ester supplement 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.

Also known as: H.V.M.N Ketone Ester food supplement

High-dose KE; Low-dose KE

Eligibility Criteria

• Age: 18 Years - 45 Years
• Gender Eligibility Details: Males
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Related Publications (13)

• 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.

  PMID: 2656155 BACKGROUND

• 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.

  PMID: 22561291 BACKGROUND

• 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.

  PMID: 25379174 BACKGROUND

• 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.

  PMID: 27475046 BACKGROUND

• 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.

  PMID: 29473164 BACKGROUND

• 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.

  PMID: 27626197 BACKGROUND

• 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.

  PMID: 27861911 BACKGROUND

• 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.

  PMID: 10702749 BACKGROUND

• 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.

  PMID: 26855664 BACKGROUND

• 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.

  PMID: 29446830 BACKGROUND

• 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.

  PMID: 27430501 BACKGROUND

• 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.

  PMID: 6986618 BACKGROUND

• 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.

  PMID: 29163194 BACKGROUND

MeSH Terms

Conditions

Diabetic Ketoacidosis

Condition Hierarchy (Ancestors)

Ketosis; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases; Diabetes Complications; Diabetes Mellitus; Endocrine System Diseases

Study Officials

• Christoph Stettler, MD

  University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: 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
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Single-centre, randomised, single blinded, crossover study in 6 individuals with type 1 diabetes (see inclusion/exclusion criteria)

Study Record Dates

• First Submitted: July 22, 2020
• First Posted: July 27, 2020
• Study Start: August 1, 2023
• Primary Completion: November 1, 2023
• Study Completion: December 1, 2023
• Last Updated: September 1, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will not share