Clinical trial NCT05584371: Evaluation of the Safety and Tolerability of Exogenous Ketosis Induced by Free Beta-hydroxybutyrate.
Official title: Evaluation of the Safety and Tolerability of Exogenous Ketosis Induced by Free Beta-hydroxybutyrate.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Exogenous Ketosis
Keywords: Exogenous ketosis
Beta-hydroxybutyrate
Safety
Tolerability
Ketone bodies
Lead sponsor: Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Sponsor class: OTHER
Collaborators: name: American Ketone LLC
First posted: 2022-10-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: The goal of this clinical trial is to evaluate the safety and tolerability of free beta-hydroxybutyrate induced ketosis in healthy individuals. The main question it aims to answer is:

* Is free beta-hydroxybutyrate safe and well tolerated by adults?

Participants will be asked to ingest 10 grams of beta-hydroxybutyrate, diluted in water and sweetened with Stevia, every morning between 9:00 and 11:00 for four weeks.

Detailed description: Several ketogenic interventions have shown benefits in a wide variety of clinical scenarios. Ketosis can be induced in different ways: by 72 hours of fasting, with a carbohydrate-restricted diet and with supplements. For emergency situations, such as heart failure, the first two options are not an option for patients as they cannot wait 72 hours.

There are 3 safe supplements for inducing ketosis: ketone salts, ketone esters and medium-chain triglycerides. Even though they all raise the beta-hydroxybutyrate serum concentration, they significantly differ in safety profiles, drug vehicles, palatability and monetary costs. A biologically identical beta-hydroxybutyrate supplement with prompt onset of action and free of salt, alcohol and drug vehicles would be an adequate option in many clinical settings.

A gender and age-balanced adult sample will be recruited in order to evaluate the safety and tolerability of free beta-hydroxybutyrate. Participants will be asked to ingest 10 grams of beta-hydroxybutyrate, diluted in water and sweetened with Stevia, every morning between 9:00 and 11:00 for four weeks. Symptoms will be evaluated on a daily basis with a self-administered opened questionnaire. A venous blood gas analysis will be made at the beginning, 2 and 4 weeks later.

Eligibility criteria: Inclusion Criteria:

* Asymptomatic adults who have not been diagnosed with chronic degenerative diseases or diseases that cause acid-base imbalances.
* Regarding women of childbearing age, it will only be recruited those who are using a method of contraception including oral contraception, contraceptive implant, contraceptive injection, intrauterine device (IUD) or patch.
* Adults without cognitive impairment that can compromise decision making.

Exclusion Criteria:

* Scheduled surgery during participation period.
* Adults on a ketogenic diet, carbohydrate-restricted diet or intermittent fasting.
* Women with a positive HCG serum or urine pregnancy test.

Primary outcomes:
measure: Symptoms
timeFrame: 4 weeks
measure: Venous blood gas analysis
timeFrame: 4 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: INCMNSZ
state: Cdmx
Study officials:
affiliation: INCMNSZ
name: Adrian Soto, PhD, MD.
role: PRINCIPAL_INVESTIGATOR
References:
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citation: American Ketone. (n.d.). Therapeutic Ketosis = Potential for New Outcomes. Retrieved June 6, 2022, from https://americanketone.com
citation: Fortier M, Castellano CA, Croteau E, Langlois F, Bocti C, St-Pierre V, Vandenberghe C, Bernier M, Roy M, Descoteaux M, Whittingstall K, Lepage M, Turcotte EE, Fulop T, Cunnane SC. A ketogenic drink improves brain energy and some measures of cognition in mild cognitive impairment. Alzheimers Dement. 2019 May;15(5):625-634. doi: 10.1016/j.jalz.2018.12.017. Epub 2019 Apr 23.
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citation: Nielsen R, Moller N, Gormsen LC, Tolbod LP, Hansson NH, Sorensen J, Harms HJ, Frokiaer J, Eiskjaer H, Jespersen NR, Mellemkjaer S, Lassen TR, Pryds K, Botker HE, Wiggers H. Cardiovascular Effects of Treatment With the Ketone Body 3-Hydroxybutyrate in Chronic Heart Failure Patients. Circulation. 2019 Apr 30;139(18):2129-2141. doi: 10.1161/CIRCULATIONAHA.118.036459.
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citation: Soto-Mota A, Norwitz NG, Evans R, Clarke K, Barber TM. Exogenous ketosis in patients with type 2 diabetes: Safety, tolerability and effect on glycaemic control. Endocrinol Diabetes Metab. 2021 May 20;4(3):e00264. doi: 10.1002/edm2.264. eCollection 2021 Jul.
citation: Soto-Mota A, Vansant H, Evans RD, Clarke K. Safety and tolerability of sustained exogenous ketosis using ketone monoester drinks for 28 days in healthy adults. Regul Toxicol Pharmacol. 2019 Dec;109:104506. doi: 10.1016/j.yrtph.2019.104506. Epub 2019 Oct 23.
citation: St-Onge MP, Jones PJ. Physiological effects of medium-chain triglycerides: potential agents in the prevention of obesity. J Nutr. 2002 Mar;132(3):329-32. doi: 10.1093/jn/132.3.329.
citation: Stubbs BJ, Cox PJ, Kirk T, Evans RD, Clarke K. Gastrointestinal Effects of Exogenous Ketone Drinks are Infrequent, Mild, and Vary According to Ketone Compound and Dose. Int J Sport Nutr Exerc Metab. 2019 Nov 1;29(6):596-603. doi: 10.1123/ijsnem.2019-0014.