NCT04421014Completed

Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults 55 Years Old or Older

Ketone Ester Effects on Biomarkers of Brain Metabolism and Cognitive Performance in Cognitively Intact Adults >= 55 Years Old. A Double-Blinded Randomized Controlled Clinical Trial.

Source: ClinicalTrials.gov · Last updated 2 Apr 2026

Brief summary (registry, in English)

Background: In Alzheimer s disease (AD) the brain cannot use glucose as a fuel. The brain can use ketones as a fuel instead of glucose. Researchers want to test a supplement, Ketone Ester (KE). It may improve brain metabolic function and cognition in normal people and, perhaps, down the road, in patients with AD. Objective: To study the change in brain ketone levels in people after 28 days of taking KE compared with baseline and placebo. Also, to study changes in cognitive performance. Eligibility: People 55 years old or older with metabolic syndrome and no cognitive impairment Design: Participants will have 4 visits. Participants will be screened at Visit 1 with: Medical history Physical exam Blood and urine tests Cognitive testing Participants will be randomly assigned to receive either the study supplement or a placebo with same amount of calories. Neither they nor the researchers will know which they receive. Visit 2 will include repeats of some screening tests. It will also include: Stool sample (brought from home) MRI/MRS: Participants will lie on a table that slides in and out of a scanner. A coil will be placed over their head. They may be asked to perform leg exercises. First dose of study supplement or placebo About 2 weeks after Visit 2, Visit 3 will include blood and urine tests and a questionnaire. About 2 weeks after Visit 3, Visit 4 will include repeats of the Visit 2 tests. Participants will drink the study supplement or placebo 3 times per day during the study. They will keep a daily log of each dose. They will bring the log to Visits 3 and 4. Participants will by contacted by phone once per week during the study to see how they are doing. ...

Status (registry): Completed
Study type: Interventional
Enrollment: 99 (actual)
First submitted: 5 Jun 2020
Start date: 24 Jun 2021
Primary completion date: 2 Jun 2025
Lead sponsor: National Institute on Aging (NIA)
Diseases: Alzheimer disease
NCT number: NCT04421014

What you commit to

Study type: Interventional
Participants enrolled: 99
From 24 Jun 2021 to the primary completion date, 2 Jun 2025
1 site in 1 country
Visits and tests: ask the trial team, the registry does not list them

Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.

Who cannot take part

Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.

Prior treatment

Previously diagnosed with a condition causing clinically significant cognitive impairment, such as MCI, AD or other type of dementia (such as vascular dementia, Lewy body dementia and frontotemporal dementia).
Chronic and significant psychiatric conditions (e.g. history of bipolar disorder, schizophrenia, PTSD, moderate to severe depression or treatment-resistant depression. Unipolar depression or anxiety disorder may be allowed if mild or if successfully treated with single anti-depressant or anti-anxiety agents.
Positive urine drug screen (and no prescription medication accounting for the positive test).
Contraindications for MRI (pregnancy, pacemakers or other implanted devices, ferrous metal implants or shrapnel in or around the head etc.).
Lactation or Pregnancy (positive urine pregnancy test. Pregnancy tests will not be done on post-menopausal women defined as one of the below criteria:
- prior bilateral oophorectomy
- Amenorrhea for 12 months or more
Taking the drug metformin.
Participant has any concurrent medical condition, so that participation in the clinical study would not be in her/his best interest, in the PI s judgement.

Other illness

History of clinically significant brain disorders, such as stroke, multiple sclerosis, Parkinson s disease or other movement disorders, brain tumors, history of meningitis or encephalitis, history of moderate or severe traumatic brain injury (defined as Glasgow Coma Scale of 12 or less), epilepsy. Certain common neurological disorders not considered relevant (e.g. migraine, essential tremor) or incidental neuroimaging findings that are common and of uncertain clinical significance (e.g. mild-moderate microvascular changes on MRI) may be allowed.
Positive HIV, HBV or HCV status during screening.
Known severe allergic reactions to the KE drinks or other ketogenic supplement or stevia products.
Severe Hypertension (systolic blood pressure \>=180 mmHg and/or diastolic blood pressure \>=120 mmHg)
Diabetes Mellitus (type 1 or 2)
To be eligible to consent for optional thigh MRI: Individuals with joint replacements that may be affected by the defined exercise protocol or which may prevent MRI analysis or any condition, in the opinion of the investigator, that would prevent successful completion of the exercise protocol such as, but not limited to reported osteoarthritis, rheumatoid arthritis and/or fibromyalgia.

Lab values

Anemia (defined as HGB \< 12 for men or \< 11 g/dl for women)
Very high or severe hypertriglyceridemia (\>=886 mg/dL or 10.0 mmol/L)

Other

An individual who meets any of the following criteria will be excluded from participation in this study:
Poor venous access.
Following high fat/low carb diet (ketogenic) diet or very low calorie (\<500 calories) diet or taking other ketogenic supplements (such as Medium Chain Triglycerides (MCTs), Ketone Salts) or fasting intermittently and unwilling to stop it while on the KE drink/Placebo.
Weight \>= 300 lbs (MRI scanner weight limit)
Non-English speakers (given staffing constraints for cognitive testing administration and need for decreased variability in testing procedures for a small N study).

Criteria the registry did not label

INCLUSION CRITERIA:
- In order to be eligible to participate in this study, an individual must meet all of the following criteria:
Ability to provide informed consent and willingness to sign a written informed consent document
Male or female, age \>=55 years old
Cognitively intact status ascertained during screening (defined as absence of significant memory or cognitive changes in the last 2 years by subjective report, Clinical Dementia Rating (CDR) of 0, and Montreal Cognitive Assessment (MoCA) \>= 26)
Ability to take oral medications
Willingness to adhere to all study procedures including having MRI/MRS.
Presence of Metabolic Syndrome (MetS). Specifically, they should meet three of the five following MetS diagnostic criteria to be eligible:
- Receive drug treatment for elevated triglycerides (TGs) or have serum TGs \>=150 mg/dL (1.7 mmol/L)
- Receive drug treatment for low HDL-cholesterol or have serum HDL-cholesterol \<40 mg/dL (1.0 mmol/L) in males; \<50 mg/dL (1.3 mmol/L) in females
- Receive drug treatment for high Blood Pressure (BP) or have BP \>=130/85 mmHg
- Receive drug treatment for high blood glucose or have fasting plasma glucose \>=100 mg/dL
- Central obesity, defined as a waist circumference \>=102 cm (40 in) in men and \>=88 cm (35 in) in women.

Age in the registry: 55 years to - · Sex: All · Does not accept healthy volunteers

Full criteria on ClinicalTrials.gov

Sites (1)

Sites in registry order. Pick your city on the disease page to sort them by distance.

Site	City	Country	Site status
National Institute of Aging, Clinical Research Unit Coordinator of this site? Confirm its status	Baltimore	United States	Unknown status

This page is information, not medical advice. Discuss any trial with your doctor.