Buck Institute Ketone Ester RCT

NCT05585762 | Completed

• 1 other identifier: BUCK_2201
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

This study is to investigate the tolerability and safety of a ketone promoting ingredient, called a ketone ester (KE), in healthy older adults. This randomized, double-blind, placebo-controlled trial aims to characterize the tolerability and safety of daily consumption of the KE in healthy older adults (over 65 years old) over 12 weeks. Study participants will complete Beverage Tolerability Questionaires (BTQ) to rate any side side effects throughout the study. Safety will also be assessed by collection of blood and urine samples, vital signs, body weight, and monitoring of adverse events (AEs). The study will also collect pilot data to explore possible effects of KE on physical function, cognitive function and quality of life. The findings of this study will be used to facilitate future mechanistic studies of KE in aging.

Conditions

Tolerance; Safety Issues; Aging

Keywords

Ketone ester; Tolerance; Safety; Aging

Outcome Measures

Primary Outcomes (1)

• Tolerance

  The primary outcome measure is the proportion of subjects reporting the same moderate to severe symptom (among dizziness, headache or nausea) occurring on more than one day within any given recall period (after week 0 - 2 acclimation period) when ketone esters are consumed daily for 12 weeks.

  12 weeks

Secondary Outcomes (2)

• Safety Blood Profile

  Change from baseline to week 4, and week 12.

• Ketone changes 4h after ketone ester drinks

  4 hours

Other Outcomes (16)

• Change in Short Physical Performance Battery Score

  Measured at baseline (Week 0) and final visit (Week 12)

• Change in 1 rep max leg press

  Measured at baseline (Week 0) and final visit (Week 12)

• Change in Sub maximal leg press to fatigue

  Measured at baseline (Week 0) and final visit (Week 12)

Study Arms (2)

Ketone ester

EXPERIMENTAL

Flavored ketone ester beverage 75 mL. Day 0 - 7: half of one bottle consumed daily. Day 8 to end (Week 12): one full bottle consumed daily.

Other: Ketone ester

Non-ketone placebo

PLACEBO COMPARATOR

Flavored beverage with bitter additive 75 mL. Matched for appearance, taste and calories. Day 0 - 7: half of one bottle consumed daily. Day 8 to end (Week 12): one full bottle consumed daily.

Other: Non-ketone placebo

Interventions

Ketone ester OTHER

75 mL chocolate flavored beverage containing 25 g of ketone ester. Half a bottle (12.5 g/day) will be consumed for the first 7 days and a complete bottle (25 g/day) will be consumed for the remaining 77 days.

Ketone ester

Non-ketone placebo OTHER

75 mL chocolate flavored beverage containing 25 g of non-ketogenic fat. Half a bottle (12.5 g/day) will be consumed for the first 7 days and a complete bottle (25 g/day) will be consumed for the remaining 77 days.

Non-ketone placebo

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Older Adult (65+)

You may qualify if:

• Subject is greater than or equal to 65 years of age, inclusive at Visit 1.
• Subject has a BMI 18.5-34.9 kg/m2 (inclusive) at Visit 1.
• Subject is willing and able to comply with all study procedures including randomization into any of the experimental groups, maintenance of habitual dietary intake, exercise and medication and supplement use, blood draws and the following prior to test visits: fasting (≥10 h; water and black coffee only), no alcohol (≥ 10 h), no cannabis products (≥10 h) and no exercise (≥ 10 h).
• Subject has no health conditions that would prevent them from fulfilling the study requirements as judged by the Clinical Investigator on the basis of medical history and routine laboratory test results.
• Subject understands the study procedures and signs forms providing informed consent to participate in the study.

You may not qualify if:

• Subject is non ambulatory
• Subject has a CSHA clinical frailty score \> 5
• Subject requires assistance with any activity of daily living
• Subject lives in an institutional setting (skilled nursing facility or residential care facility for the elderly).
• Subject is a female who has not passed menopause.
• Subject is unable to converse in English
• Subject is unable to provide informed consent due to cognitive impairment or insufficient English language comprehension
• Subject has been hospitalized within 30 days of Visit 1, 2 or 3.
• Subject has an abnormal laboratory test result(s) of clinical importance, indicating unstable chronic disease of major organ dysfunction, at Visit 1, at the discretion of the Medical Officer. One re-test will be allowed on a separate day prior to Visit 2, for subjects with abnormal laboratory test results.
• Subject has a clinically important gastrointestinal condition that would potentially interfere with the evaluation of the study beverage \[e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation, severe constipation (in the opinion of the Clinical Investigator), history of frequent diarrhea, history of surgery for weight loss, gastroparesis, systemic disease that might affect gut motility according to the Investigator, reflux requiring daily medication, history of gastrointestinal ulcers or bleeding, and/or clinically important lactose intolerance\].
• Subject has a history of alcohol or substance abuse.
• Subject is consistently using prescriptive or over-the counter medications where alcohol is a contraindication at the discretion of the Investigator.
• Subject has a known allergy, intolerance, or sensitivity to any of the ingredients in the study beverages, including soy and milk protein.
• Subject has uncontrolled hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg) as defined by the blood pressure measured at Visit 1. One re-test will be allowed on a separate day before Visit 2, for subjects with abnormal blood pressure.
• Subject is undergoing treatment or active surveillance for cancer, or has been diagnosed with cancer in the prior two years, except for non-melanoma skin cancer.

Sponsors & Collaborators

• Buck Institute for Research on Aging: lead
• Biofortis Mérieux NutriSciences: collaborator

Study Sites (1)

Buck Institute for Research on Aging

Novato, California, 94945, United States

Location

Related Publications (6)

• Chen O, Blonquist TM, Mah E, Sanoshy K, Beckman D, Nieman KM, Winters BL, Anthony JC, Verdin E, Newman JC, Stubbs BJ. Tolerability and Safety of a Novel Ketogenic Ester, Bis-Hexanoyl (R)-1,3-Butanediol: A Randomized Controlled Trial in Healthy Adults. Nutrients. 2021 Jun 16;13(6):2066. doi: 10.3390/nu13062066.

  PMID: 34208742 BACKGROUND

• Crabtree CD, Blade T, Hyde PN, Buga A, Kackley ML, Sapper TN, Panda O, Roa-Diaz S, Anthony JC, Newman JC, Volek JS, Stubbs BJ. Bis Hexanoyl (R)-1,3-Butanediol, a Novel Ketogenic Ester, Acutely Increases Circulating r- and s-ss-Hydroxybutyrate Concentrations in Healthy Adults. J Am Nutr Assoc. 2023 Feb;42(2):169-177. doi: 10.1080/07315724.2021.2015476. Epub 2022 Mar 25.

  PMID: 35512774 BACKGROUND

• Stubbs BJ, Stephens EB, Mansfield T, Senadheera C, Diaz SR, Peralta S, Alexander L, Silverman-Martin W, Kurtzig J, Fernando BA, Garcia TY, Yukawa M, Morris J, Yurkovich JT, Newman AB, Johnson JB, Cawthon PM, Newman JC. Exploratory functional and quality of life outcomes with daily consumption of the ketone ester bis-octanoyl (R)-1,3-butanediol in healthy older adults: a randomized, parallel arm, double-blind, placebo-controlled study. J Frailty Aging. 2025 Dec;14(6):100106. doi: 10.1016/j.tjfa.2025.100106. Epub 2025 Nov 27.

  PMID: 41313689 DERIVED

• Stubbs BJ, Stephens EB, Senadheera C, Diaz SR, Peralta S, Alexander L, Silverman-Martin W, Kurtzig J, Fernando BA, Yurkovich JT, Garcia TY, Yukawa M, Morris J, Johnson JB, Newman JC. Exploratory functional and quality of life outcomes with daily consumption of the ketone ester bis-octanoyl (R)-1,3-butanediol in healthy older adults: a randomized, parallel arm, double-blind, placebo-controlled study. medRxiv [Preprint]. 2024 Sep 18:2024.09.17.24313811. doi: 10.1101/2024.09.17.24313811.

  PMID: 39371165 DERIVED

• Stubbs BJ, Stephens EB, Senadheera C, Peralta S, Roa-Diaz S, Alexander L, Silverman-Martin W, Garcia TY, Yukawa M, Morris J, Blonquist TM, Johnson JB, Newman JC. Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, placebo-controlled, pilot study. J Nutr Health Aging. 2024 Sep;28(9):100329. doi: 10.1016/j.jnha.2024.100329. Epub 2024 Aug 12.

  PMID: 39137624 DERIVED

• Stubbs BJ, Stephens EB, Senadheera C, Peralta S, Roa-Diaz S, Alexander L, Silverman-Martin W, Garcia TY, Yukawa M, Morris J, Blonquist TM, Johnson JB, Newman JC. Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults, a randomized, parallel arm, double-blind, placebo-controlled, pilot study. medRxiv [Preprint]. 2024 May 5:2024.05.03.24306699. doi: 10.1101/2024.05.03.24306699.

  PMID: 38746215 DERIVED

MeSH Terms

Interventions

formic acid 4-(3-oxobutyl)phenyl ester

Study Officials

• John C Newman, MD, PhD

  Buck Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study products will be allocated a code and labelled by an external team. The coding of the study products will be recorded and sealed in 'unblinding envelopes' that will only be opened in unblinding becomes necessary for subject safety. No one on the study team (including outcome assessor and statisticians) will be aware of the study product identity. The study products are matched for appearance, taste and calories and will not be visibly distinguishable.
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel group, randomized, double-blind.

Study Record Dates

• First Submitted: October 3, 2022
• First Posted: October 19, 2022
• Study Start: November 28, 2022
• Primary Completion: December 13, 2023
• Study Completion: January 17, 2024
• Last Updated: June 11, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)