ToleranceBIKENCT05585762
Buck Institute Ketone Ester RCT
A study testing Ketone ester in people with Tolerance and Safety Issues, run by Buck Institute for Research on Aging at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 65 years and olderHealthy volunteers can take part
- Conditions the study is for
- Tolerance, Safety Issues, Aging
- What is being tested?
- Ketone ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- 28 Nov 2022to 17 Jan 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- Healthy volunteers accepted
- Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 26Show fewer
- 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 history or presence of uncontrolled and/or clinically active pulmonary, cardiac (e.g. >= New York Heart Association class III), hepatic, renal, endocrine (including type 1 diabetes), hematologic, immunologic, neurologic (e.g., Alzheimer's or Parkinson's diseases), psychiatric (including unstable depression and/or anxiety disorders) or biliary disorders. Stable chronic disease is not an exclusion criterion unless specified.
- 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.
- Subject has recently used antibiotics within 30 days of Visit 1, 2 or 3.
- Subject has extreme dietary habits (e.g., intermittent fasting or time restricted eating, Atkins diet, vegan, very high protein/low carbohydrate or has used weight-loss medications (including over-the-counter medications and/or supplements) or programs within 30 days of Visit 1, 2 or 3.
- Subject has used medications (over-the-counter or prescription) known to influence gastrointestinal function including, but not limited to, opioids, weight loss medications, antidiarrheals, and antispasmodics) within 30 days of Visit 1, 2 or 3.
- Subject has used ketone supplements (ketone salts or esters, and medium chain triglycerides [MCT]) within 30 days of Visit 1, 2 or 3.
- Subject has unstable use of thyroid, antihypertensive, antidepressant, or statin medications within 30 days of Visit 1, 2 or 3.
- Subject has a condition the Clinical Investigator believes would interfere with their ability to provide informed consent, comply with the study protocol, which might confound the interpretation of the study results, or put the subject at undue risk.
- Subject works nights or shifts that means it is not possible to maintain a consistent meal schedule during the study.
- Subject is not permitted to visit the Buck Institute campus, for example due to inability to confirm COVID-19 vaccination status.
- Subject does not have a Bluetooth enabled smartphone.
- Subject does not have access to the internet
Trial locations and contacts
1 site in 1 country.
United States1 site
Buck Institute for Research on Aging
Novato, California, 94945
About this study
Official title: A Randomized, Double-blind, Placebo-controlled, Parallel Group, Feasibility Pilot Study to Evaluate the Tolerability and Safety of a Novel Ketone Ester Ingredient in Healthy Older Men and Women.
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.
Read the detailed description
Screening (Phone and Visit 1): Subjects are screened for eligibility by telephone for major exclusion criteria. They then attend a screening visit. At the start of the visit subjects must meet pre-test requirements (fasting ≥ 10 h, no alcohol ≥ 10 h, no exercise ≥ 10 h, no cannabis products ≥ 10 h). During this visit, consent is obtained, followed by a medical history interview, a physical assessment (including vital signs, body weight, and waist circumference) and fasting blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is also collected for urinalysis. Subjects eligible and willing to take part in the study are randomized to take one of the two ketone ester serving sizes (12.5 g , 25 g) for the ketone kinetics visit (Visit 2). Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days before Visit 2, the stool sample will be returned to investigators using a prepaid mailer.
Ketone Kinetics Visit (Visit 2): Subjects must meet pre-test requirements (as above). A BTQ (Beverage Tolerability Questionnaire) is used to observe the tolerability of ketone drinks before and after their consumption. Blood glucose and ketone levels are measured from a finger stick sample of a ketone meter at baseline, and at 30, 60, 90,120,180, 240-minute timepoints. Subjects are then randomized to their experimental group ketone ester or placebo for the remainder of the visits (Visit 3-5). Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days before Visit 3; samples are returned by mail.
Baseline Visit (Visit 3- Week 0): Subjects must meet pre-test requirements (as above). Fasted blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is collected for screening analysis and urinalysis and additional plasma is banked for future aging biomarker analysis. Subjects will undergo an interview for Katz's Activities of Daily Living (ADL), and Lawton's Instrumental Activities of Daily Living (IADLs), and CSHA Frailty Score (Canadian Study of Health and Aging). Subjects also complete the following paper questionnaires: Profile of Mood States (Short form), The Sexual Quality of Life Questionnaire (Male or Female Version), Short Form Health Survey-36, Pittsburgh Sleep Quality Index, Pittsburgh Fatiguability Scale and Geriatric Depression Scale. Physical and cognitive measures are assessed through the following tests: Montreal Cognitive Assessment, Digit Symbol Substitution Task and Trails A and B. Subjects also complete physical function testing at baseline (Visit 3) and final visit (Visit 5): Short Physical Performance Battery, 1 rep max leg press, sub maximal leg press repetitions to failure, 6-minute walk test and grip strength.
At the end of the testing, a continuous glucose and ketone monitor is applied (lasting 2 weeks). Subjects will be given a stool sample collection kit to take home for at-home sample between Week 1 and 2; samples are returned by mail. Subject will be given a month's supply of study product to take home. Subjects will be reminded of study instructions (for study beverage consumption, daily Study Log completion, and to maintain habitual exercise, meal/diet, and medication/supplementation use).
At home procedures (Week 0 - 12): Each day at home, subjects should consume their first meal of the day at a similar time and consume the study product within 5 minutes of finishing their first meal. Subjects will complete the Study Log immediately before they consume their second meal of the day or a snack (3 - 6 h after the study beverage). For Days 1 - 14 the Study Log will query the presence of specific symptoms with a beverage tolerance questionnaire (BTQ) and will confirm that subjects consumed their study product. From Day 15 onwards, the Study Log records study product consumption, but a full BTQ is not completed; however, any symptoms can be noted to assess tolerance by interview for the previous 2-week interval; at Visit 4- Week 4, during phone check-ins (Week 5, 8, and 10) and at Visit 5. At Week 8, subjects will be mailed the final mont's supply of study product, a continuous glucose and ketone sensor to apply at home (Week 10), and a stool sample collection kit for at-home sample collection up to 3 days before Visit 5 (Week 12), samples are returned by mail.
Intermediate Visit (Visit 4- Week 4): Subjects must meet pre-test requirements (as above). Fasted blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is collected for screening analysis and urinalysis and additional plasma is banked for future aging biomarker analysis. Tolerance of the study beverage and Adverse Events are assessed by interview. Subjects will be given a month's supply of study product to take home. Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days after Visit 4; samples are returned by mail.
Final Visit (Visit 5- Week 12): Follows identical testing procedures to Baseline Visit (Visit 3, Week 0).
- Conditions
- Tolerance, Safety Issues, Aging
- Being tested
- Ketone ester, Non-ketone placebo
- Keywords
- Ketone ester, Tolerance, Safety, Aging
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone esterOther
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.
Non-ketone placeboOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Other: Non-ketone placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 weeks
Secondary outcomes (2)
Safety Blood Profile
Change from baseline to week 4 and week 12 in the incidence of abnormal laboratory test results
Measured: Change from baseline to week 4, and week 12.
Ketone changes 4h after ketone ester drinks
Subjects consume a single serving of either 12.5 g or 25 g of ketone ester. After this, their short-term (regularly over 4h) blood ketone changes are measured using capillary blood sampling.
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Oct 2022
- Study start28 Nov 2022
- Primary completion13 Dec 2023
- Study completion17 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for ToleranceStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel group, randomized, double-blind.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Buck Institute for Research on Aging
- Sponsor type
- University, hospital or other
- Collaborators
- Biofortis Mérieux NutriSciences
- Responsible party
- Sponsor
- Investigators
- John C Newman, MD, PhD, Principal investigator, Buck Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05585762
- Sponsor's protocol ID
- BUCK_2201
- Acronym
- BIKE
- Status last verified
- Jan 2024
- First submitted
- 3 Oct 2022
- Last updated
- 11 Jun 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 34208742Crabtree 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.
PubMed 35512774Stubbs 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.
PubMed 41313689Stephens EB, Senadheera C, Roa-Diaz S, Peralta S, Alexander L, Silverman-Martin W, Yukawa M, Morris J, Johnson JB, Newman JC, Stubbs BJ. A Randomized Open-Label, Observational Study of the Novel Ketone Ester, Bis Octanoyl (R)-1,3-Butanediol, and Its Acute Effect on ss-Hydroxybutyrate and Glucose Concentrations in Healthy Older Adults. J Nutr Gerontol Geriatr. 2025 Apr-Jun;44(2):103-122. doi: 10.1080/21551197.2025.2466163. Epub 2025 Feb 22.
PubMed 39985761Stubbs 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.
PubMed 39371165Stubbs 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.
PubMed 39292659Stubbs 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.
PubMed 39137624Stubbs 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.
PubMed 38746215
Study at a glance
From the registry record, last updated by the sponsor on 11 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-blind, Placebo-controlled, Parallel Group, Feasibility Pilot Study to Evaluate the Tolerability and Safety of a Novel Ketone Ester Ingredient in Healthy Older Men and Women.
- ClinicalTrials.gov ID
- NCT05585762
- Acronym / sponsor ID
- BIKE / BUCK_2201
- Conditions
- Tolerance, Safety Issues, Aging
- Keywords
- Ketone ester, Tolerance, Safety, Aging
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Buck Institute for Research on AgingUniversity, hospital or other
- Collaborators
- Biofortis Mérieux NutriSciences
- Study start
- 28 Nov 2022 (actual)
- Primary completion
- 13 Dec 2023 (actual)
- Study completion
- 17 Jan 2024 (actual)
- First posted
- 19 Oct 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Screening (Phone and Visit 1): Subjects are screened for eligibility by telephone for major exclusion criteria. They then attend a screening visit. At the start of the visit subjects must meet pre-test requirements (fasting ≥ 10 h, no alcohol ≥ 10 h, no exercise ≥ 10 h, no cannabis products ≥ 10 h). During this visit, consent is obtained, followed by a medical history interview, a physical assessment (including vital signs, body weight, and waist circumference) and fasting blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is also collected for urinalysis. Subjects eligible and willing to take part in the study are randomized to take one of the two ketone ester serving sizes (12.5 g , 25 g) for the ketone kinetics visit (Visit 2). Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days before Visit 2, the stool sample will be returned to investigators using a prepaid mailer.
Ketone Kinetics Visit (Visit 2): Subjects must meet pre-test requirements (as above). A BTQ (Beverage Tolerability Questionnaire) is used to observe the tolerability of ketone drinks before and after their consumption. Blood glucose and ketone levels are measured from a finger stick sample of a ketone meter at baseline, and at 30, 60, 90,120,180, 240-minute timepoints. Subjects are then randomized to their experimental group ketone ester or placebo for the remainder of the visits (Visit 3-5). Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days before Visit 3; samples are returned by mail.
Baseline Visit (Visit 3- Week 0): Subjects must meet pre-test requirements (as above). Fasted blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is collected for screening analysis and urinalysis and additional plasma is banked for future aging biomarker analysis. Subjects will undergo an interview for Katz's Activities of Daily Living (ADL), and Lawton's Instrumental Activities of Daily Living (IADLs), and CSHA Frailty Score (Canadian Study of Health and Aging). Subjects also complete the following paper questionnaires: Profile of Mood States (Short form), The Sexual Quality of Life Questionnaire (Male or Female Version), Short Form Health Survey-36, Pittsburgh Sleep Quality Index, Pittsburgh Fatiguability Scale and Geriatric Depression Scale. Physical and cognitive measures are assessed through the following tests: Montreal Cognitive Assessment, Digit Symbol Substitution Task and Trails A and B. Subjects also complete physical function testing at baseline (Visit 3) and final visit (Visit 5): Short Physical Performance Battery, 1 rep max leg press, sub maximal leg press repetitions to failure, 6-minute walk test and grip strength.
At the end of the testing, a continuous glucose and ketone monitor is applied (lasting 2 weeks). Subjects will be given a stool sample collection kit to take home for at-home sample between Week 1 and 2; samples are returned by mail. Subject will be given a month's supply of study product to take home. Subjects will be reminded of study instructions (for study beverage consumption, daily Study Log completion, and to maintain habitual exercise, meal/diet, and medication/supplementation use).
At home procedures (Week 0 - 12): Each day at home, subjects should consume their first meal of the day at a similar time and consume the study product within 5 minutes of finishing their first meal. Subjects will complete the Study Log immediately before they consume their second meal of the day or a snack (3 - 6 h after the study beverage). For Days 1 - 14 the Study Log will query the presence of specific symptoms with a beverage tolerance questionnaire (BTQ) and will confirm that subjects consumed their study product. From Day 15 onwards, the Study Log records study product consumption, but a full BTQ is not completed; however, any symptoms can be noted to assess tolerance by interview for the previous 2-week interval; at Visit 4- Week 4, during phone check-ins (Week 5, 8, and 10) and at Visit 5. At Week 8, subjects will be mailed the final mont's supply of study product, a continuous glucose and ketone sensor to apply at home (Week 10), and a stool sample collection kit for at-home sample collection up to 3 days before Visit 5 (Week 12), samples are returned by mail.
Intermediate Visit (Visit 4- Week 4): Subjects must meet pre-test requirements (as above). Fasted blood samples are collected for screening analysis of: clinical chemistry, hematology, lipid profile, thyroid hormones. A clean catch urine sample is collected for screening analysis and urinalysis and additional plasma is banked for future aging biomarker analysis. Tolerance of the study beverage and Adverse Events are assessed by interview. Subjects will be given a month's supply of study product to take home. Subjects will be given a stool sample collection kit to take home for at-home sample collection up to 3 days after Visit 4; samples are returned by mail.
Final Visit (Visit 5- Week 12): Follows identical testing procedures to Baseline Visit (Visit 3, Week 0).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel group, randomized, double-blind.
| Arm | Type | Receives |
|---|---|---|
| Ketone ester | Experimental | Other: Ketone esterFlavored 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. |
| Non-ketone placebo | Placebo comparator | Other: Non-ketone placeboFlavored 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. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (26 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ketone ester75 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. | Other | Ketone ester |
| Non-ketone placebo75 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. | Other | Non-ketone placebo |
Primary outcome
Tolerance
Time frame: 12 weeks
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.
2 secondary outcomes
Safety Blood Profile
Time frame: Change from baseline to week 4, and week 12.
Ketone changes 4h after ketone ester drinks
Time frame: 4 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Jun 2024.
- Background: PubMed 34208742Chen 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.
- Background: PubMed 35512774Crabtree 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.
- Derived from this study: PubMed 41313689Stubbs 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.
- Derived from this study: PubMed 39985761Stephens EB, Senadheera C, Roa-Diaz S, Peralta S, Alexander L, Silverman-Martin W, Yukawa M, Morris J, Johnson JB, Newman JC, Stubbs BJ. A Randomized Open-Label, Observational Study of the Novel Ketone Ester, Bis Octanoyl (R)-1,3-Butanediol, and Its Acute Effect on ss-Hydroxybutyrate and Glucose Concentrations in Healthy Older Adults. J Nutr Gerontol Geriatr. 2025 Apr-Jun;44(2):103-122. doi: 10.1080/21551197.2025.2466163. Epub 2025 Feb 22.
- Derived from this study: PubMed 39371165Stubbs 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.
- Derived from this study: PubMed 39292659Stubbs 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.
- Derived from this study: PubMed 39137624Stubbs 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.
- Derived from this study: PubMed 38746215Stubbs 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.
- Individual participant dataSharing planned: No
Related trials for Tolerance
Not yet recruiting
A Crossover Study Evaluating the Postprandial Glycemic Response of Three Sweeteners in a Mixed Meal Setting
Postprandial Glucose, GI Tolerance
RecruitingEarly Phase 1
Addition of Venetoclax to Combined Hematopoietic Stem Cell and Kidney Transplantation
Kidney Failure Chronic, Stem Cell Transplant
Active, not recruitingObservational study
Effects of External Upper Limb Loading on Gait and Trunk Muscle Activity in Cardiac Rehabilitation Patients
Cardiovascular Diseases, Cardiac Rehabilitation
RecruitingPhase 2
Effects of Different Fish Oil Types on Type 2 Diabetes Risk Factors in High-Risk Adults
Type 2 Diabetes, Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)
Active, not recruitingPhase 2
Effect of Probiotics Versus Metformin on Glycemic Control, Insulin Sensitivity and Insulin Secretion in Prediabetes.
PreDiabetes, Impaired Glucose Tolerance
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
John C Newman, MD, PhD principal investigator
Buck Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone ester in people with Tolerance and Safety Issues, run by Buck Institute for Research on Aging at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Jun 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Tolerance (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05585762, which also lists 8 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Jun 2024; AzTrials last refreshed its copy on 2 Nov 2026.