A Randomized, Double-blind, Placebo-controlled, Parallel Group, Pilot Study to Evaluate the Effect of a Ketone Ester on Muscle and Immune Function in Older Men and Women Who Are at Risk for Strength and Mobility Decline
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 180
- 试验地点
- 3
- 主要终点
- Frailty composite score
研究概览
简要总结
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).
详细描述
Screening (Phone and Visit 0):
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. During this visit, consent is obtained, followed by a medical history interview, a physical assessment and fasting blood samples are collected for screening analysis. Subjects who meet all the inclusion and none of the exclusion criteria will be scheduled for a Baseline (Visit 1) and at the end of Visit 1 will be randomized into one of the two experimental groups (ketone ester or placebo). Subjects will be shown and instructed on the use of the equipment for the physical function testing and complete a brief familiarization. A 24h diet log will be provided to complete before the next visit. A stool collection kit will also be provided along with use instructions to complete 3 days before Baseline visit.
Baseline Visit (Visit 1- Week 0):
Subjects must meet pre-test requirements. Changes to the subject's health and medication/supplement use will be assessed, and subject's compliance with inclusion/exclusion criteria will be reviewed. Fasted blood samples are collected. A clean catch urine sample is collected for archiving and additional plasma is banked for future aging biomarker analysis. After this a physical assessment will be conducted, including vital signs (after 5 minutes of rest), body weight and waist circumference. Investigators will reassess 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). Then subjects will complete the following paper questionnaires: Profile of Mood States (Short form), Short Form Health Survey-36, Pittsburgh Sleep Quality Index, Pittsburgh Fatiguability Scale, Geriatric Depression Scale, Lower Urinary Tract Symptom Questionnaire. Subjects will complete cognitive function testing: Montreal Cognitive Assessment, Digit Symbol Substitution Task and Trails A and B. Subjects will complete physical function testing: Short Physical Performance Battery, 1 rep max leg press, sub maximal leg press repetitions to failure, 6-minute walk test and grip strength. Subjects will be given a stool sample collection kit to take home for at-home sample between Week 0 and 1; 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 product consumption, daily Study Log completion, and to maintain habitual exercise, meal/diet, and medication/supplementation use). Subjects will be given a wearable actigraphy device and instructed on its use during the study.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •Subject is non ambulatory.
- •Subject has a CSHA clinical frailty score >
- •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 history or presence of acute or uncontrolled and/or clinically active pulmonary (chronic obstructive pulmonary disease >= Gold 3), cardiac (e.g. >= New York Heart Association class III), hepatic (cirrhosis), renal (chronic kidney disease stage >= IIIb), 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. "Uncontrolled" and "clinically active" are per the judgement of the Medical Officer. Stable chronic disease is not an exclusion criterion unless specified. Chronic disease that is managed with the patient's physician per shared decision-making, even if sub optimally by typically recommended care, is not an exclusion criterion unless uncontrolled or clinically active.
- •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.
- •Subject has uncontrolled hypertension as defined by the blood pressure measured at Screening. For subjects with elevated blood pressure at Screening, they are allowed for the purpose of this criteria to submit home readings from three separate days, or to have a repeat reading taken at the study site on a separate day before Visit
- •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. Active surveillance is defined as regular imaging or laboratory tests at a frequency greater than annually. Cancer under long-term monitoring such as stable chronic lymphocytic leukemia need not be an exclusion, on the discretion of the Medical Officer.
- •Immunosuppressive disorders, taking immunosuppressive medications (including oral prednisone >10mg/day and biological immunosuppressants), or receiving chemotherapy.
- •Chronic antibiotic use (e.g. expected to be ongoing, regardless of frequency, throughout the study period).
- •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 Screening.
- •Subject has followed a ketogenic diet or used ketone supplements (ketone salts or esters, and medium chain triglycerides) within 30 days of Screening.
- •Subject has a condition the Medical Officer 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.
研究组 & 干预措施
Ketone ester
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
干预措施: Ketone ester (Other)
Non-ketone placebo
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
干预措施: Placebo Comparator: Non-ketone placebo (Other)
结局指标
主要结局
Frailty composite score
时间窗: Baseline, 12 weeks, 20 weeks
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.
次要结局
- 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)
- Montreal Cognitive Assessment(Baseline, 12 weeks, 20 weeks)
- Trails A and B(Baseline, Week 12, Week 20)