Targeting Aging With a Ketone Ester for Function in Frailty

NCT06645847 | Recruiting

• 1 other identifier: 2024H0061
• Study Type: interventional
• Target: 180
• Locations: 1 country
• Sites: 3

Brief Summary

This study aims to find out if a food supplement that contains a naturally occurring substance, ketones, can help to improve strength and general wellness in adults at, or over the age of 65 years who are experiencing a slight decline in their physical function. Participation will involve a screening visit and 4 additional study visits over the course of 20 weeks. After being assessed for eligibility, study participants will be sorted into two groups at random and consume either a ketone or placebo supplement at home every day for 20 weeks. Both study products can cause gastro-intestinal side effects in some individuals. At all study visits, subjects will provide blood samples. At three study visits, subjects will be asked to complete physical performance tests, provide blood, stool and urine samples. They will also complete questionnaires during three study visits to assess physical function, markers of inflammation, and other aspects of general well-being. The study enrolls at three sites across the United States, in California (Buck Institute), Ohio (Ohio State University), and Connecticut (University of Connecticut). The study is coordinated by the San Francisco Coordinating Center (California Pacific Medical Center).

Conditions

Frail Elderly; Aging; Immune Function; Muscle Function

Keywords

ketone ester; exogenous ketone

Outcome Measures

Primary Outcomes (1)

• Frailty composite score

  The primary outcome measure is the difference in the change in a four-item composite score of vigor-frailty (6 minute walk, 1 rep max leg press, digit symbol substitution, Pittsburg Fatigability Scale - Physical sub scale) over 20 weeks between groups. The original composite score was developed by the Study of Muscle Mass and Aging Group, it is continuous, and a higher score corresponds to better function.

  Baseline, 12 weeks, 20 weeks

Secondary Outcomes (7)

• Tolerability key symptom index

  20 weeks

• Safety Lab Tests

  Baseline, Week 4, Week 12, 20 weeks

• Leg fatigue - leg press at sub maximal weight

  20 weeks

• Short Physical Performance Battery

  Baseline, Week 12, 20 weeks

• Grip Strength

  Baseline, Week 12, Week 20

Other Outcomes (13)

• Immune phenotyping

  20 weeks

• Changes in gut microbial diversity

  Baseline, Week 1, Week 4, Week 12, Week 20

• Profile of Mood States

  Baseline, Week 12, Week 20

Study Arms (2)

Ketone ester

ACTIVE COMPARATOR

Ketone ester (KE) (Chemical name: Bis-octanoyl-(R)-1,3-butanediol, Common name: C8 ketone di-ester) formulated as a dietary supplement. KE 12.5 g per day for 1 week; followed by KE 25 g per day for 1 week; followed by KE 37.5 g per day split into two doses for 1 week; followed by KE 50 g per day split into two doses for 17 weeks

Other: Ketone ester

Non-ketone placebo

PLACEBO COMPARATOR

Placebo oil (non-ketogenic canola oil) formulated as a dietary supplement. Placebo oil 12.5 g per day for 1 week; followed by Placebo oil 25 g per day for 1 week; followed by Placebo oil 37.5 g per day split into two doses for 1 week; followed by Placebo oil 50 g per day split into two doses for 17 weeks

Other: Placebo Comparator: Non-ketone placebo

Interventions

Ketone ester OTHER

Ketone ester (KE) (Chemical name: Bis-octanoyl-(R)-1,3-butanediol, Common name: C8 ketone di-ester) formulated as a dietary supplement. KE 12.5 g per day for 1 week; followed by KE 25 g per day for 1 week; followed by KE 37.5 g per day split into two doses for 1 week; followed by KE 50 g per day split into two doses for 17 weeks

Ketone ester

Placebo Comparator: Non-ketone placebo OTHER

Placebo oil (non-ketogenic canola oil) formulated as a dietary supplement. Placebo oil 12.5 g per day for 1 week; followed by Placebo oil 25 g per day for 1 week; followed by Placebo oil 37.5 g per day split into two doses for 1 week; followed by Placebo oil 50 g per day split into two doses for 17 weeks

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 Screening.
• Passes the gait speed criteria at Screening.
• Minimum body weight of 50 kgs at Screening.
• 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 only), no alcohol (≥ 10 h), no cannabis products (≥10 h) and no exercise (≥ 10 h).
• Subject understands the study procedures and can provide 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, excluding continence.
• 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 (or Spanish, if available at the study site).
• Subject has been hospitalized within 30 days of Screening.
• Subject has any physical limitation that would prevent them from performing 1RM leg press based on Medical Officer judgement.
• Subject has an abnormal laboratory test result(s) of clinical importance at Screening, indicating unstable chronic disease of major organ dysfunction that requires urgent evaluation, at the discretion of the Medical Officer. One re-test will be allowed on a separate day prior to Visit 1, for subjects with abnormal laboratory test results. Additional clinical information may be gathered from the participant if needed to interpret the urgency of laboratory abnormalities (e.g. recent laboratory trends if an electrolyte is abnormal).
• Subject has uncontrolled hypercholesterolemia on screening labs.
• Subject has a clinically important gastrointestinal condition that would potentially interfere with the evaluation of the study beverage \[e.g., inflammatory bowel disease, irritable bowel syndrome, chronic constipation, severe constipation (in the opinion of the Medical Officer), history of frequent diarrhea, history of surgery for weight loss, gastroparesis, systemic disease that might affect gut motility according to the Investigator, history of gastrointestinal ulcers or bleeding, history of pancreatitis, history of hiatal hernia, history of Barrett's esophagus, or history of esophageal cancer\].
• Heavy drinking (For women, 8 or more drinks per week. For men, 15 or more drinks per week).
• Subject has a history of alcohol or substance abuse.
• Subject has been instructed not to consume alcohol for medical reasons.
• Subject has a known, clinically important allergy, intolerance, or sensitivity to any of the ingredients in the study beverages, including soy and milk protein.

Sponsors & Collaborators

• California Pacific Medical Center Research Institute: collaborator
• Buck Institute for Research on Aging: lead
• Ohio State University: collaborator
• University of Connecticut: collaborator

Study Sites (3)

Buck Institute for Research on Aging

Novato, California, 94945, United States

RECRUITING

UConn Health

Farmington, Connecticut, 06030, United States

RECRUITING

Ohio State University

Columbus, Ohio, 43210, United States

RECRUITING

Related Publications (3)

• Stubbs BJ, Alvarez Azanedo G, Peralta S, Diaz SR, Gray W, Alexander L, Silverman-Martin W, Garcia TY, Blonquist TM, Upadhyay V, Turnbaugh PJ, Johnson JB, Newman JC. Rationale and protocol for a safety, tolerability and feasibility randomized, parallel arm, double-blind, placebo-controlled, pilot study of a novel ketone ester targeting frailty via immunometabolic geroscience mechanisms. PLoS One. 2024 Sep 18;19(9):e0307951. doi: 10.1371/journal.pone.0307951. eCollection 2024.

  PMID: 39292659 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

• 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

MeSH Terms

Interventions

formic acid 4-(3-oxobutyl)phenyl ester

Study Officials

• John Newman, MD, PhD

  Buck Institute

  PRINCIPAL INVESTIGATOR

• Jeff Volek, Phd

  Ohio State University

  PRINCIPAL INVESTIGATOR

• Jenna Bartley, PhD

  University of Connecticut

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Brianna Stubbs, DPhil

CONTACT

415-209-2000; bstubbs@buckinstitute.org

Chatura Senadheera, MSc

CONTACT

415-209-2072; csenadheera@buckinstitute.org

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 physical and electronic 'unblinding envelopes' that will only be opened by specific personnel if 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: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel group, randomized, double-blind, placebo controlled

Study Record Dates

• First Submitted: October 14, 2024
• First Posted: October 17, 2024
• Study Start: February 5, 2025
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): April 1, 2028
• Last Updated: March 13, 2026

Record last verified: 2026-03

Locations

US (3)