This study is currently recruiting participants.
Number
20-AG-0087
Sponsoring Institute
National Institute on Aging (NIA)
Recruitment Detail
Type: Participants currently recruited/enrolled Gender: Male & Female Min Age: 55 Years Max Age: N/A
Referral Letter Required
No
Population Exclusion(s)
Non-English Speaking;Children
Keywords
Ketogenic; Brain Metabolism; BETA-HYDROXYBUTYRATE; Dietary Supplement; Alzheimer's Disease
Recruitment Keyword(s)
None
Condition(s)
Metabolic Syndrome; Normal Cognition
Investigational Drug(s)
Investigational Device(s)
Intervention(s)
Dietary Supplement: Ketone Ester drink Dietary Supplement: Placebo: isocaloric dextrose drink
Supporting Site
National Institute on Aging
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.
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INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Ability to provide informed consent and willingness to sign a written informed consent document 2. Male or female, age >=55 years old 3. 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) 4. Ability to take oral medications 5. Willingness to adhere to all study procedures including having MRI/MRS. 6. 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. EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study: 1. 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). 2. 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. 3. 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. 4. Positive urine drug screen (and no prescription medication accounting for the positive test). 5. Positive HIV, HBV or HCV status during screening. 6. Contraindications for MRI (pregnancy, pacemakers or other implanted devices, ferrous metal implants or shrapnel in or around the head etc.). 7. Anemia (defined as HGB < 12 for men or < 11 g/dl for women) 8. Poor venous access. 9. Lactation or Pregnancy (positive urine pregnancy test. Pregnancy tests will not be done on post-menopausal women defined as one of the below criteria: a. prior bilateral oophorectomy b. Amenorrhea for 12 months or more 10. Known severe allergic reactions to the KE drinks or other ketogenic supplement or stevia products. 11. 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. 12. Very high or severe hypertriglyceridemia (>=886 mg/dL or 10.0 mmol/L) 13. Severe Hypertension (systolic blood pressure >=180 mmHg and/or diastolic blood pressure >=120 mmHg) 14. Weight >= 300 lbs (MRI scanner weight limit) 15. Diabetes Mellitus (type 1 or 2) 16. Taking the drug metformin. 17. Non-English speakers (given staffing constraints for cognitive testing administration and need for decreased variability in testing procedures for a small N study). 18. 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. 19. 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.
In order to be eligible to participate in this study, an individual must meet all of the following criteria:
1. Ability to provide informed consent and willingness to sign a written informed consent document
2. Male or female, age >=55 years old
3. 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)
4. Ability to take oral medications
5. Willingness to adhere to all study procedures including having MRI/MRS.
6. 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.
EXCLUSION CRITERIA:
An individual who meets any of the following criteria will be excluded from participation in this study:
1. 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).
2. 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.
3. 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.
4. Positive urine drug screen (and no prescription medication accounting for the positive test).
5. Positive HIV, HBV or HCV status during screening.
6. Contraindications for MRI (pregnancy, pacemakers or other implanted devices, ferrous metal implants or shrapnel in or around the head etc.).
7. Anemia (defined as HGB < 12 for men or < 11 g/dl for women)
8. Poor venous access.
9. Lactation or Pregnancy (positive urine pregnancy test. Pregnancy tests will not be done on post-menopausal women defined as one of the below criteria:
a. prior bilateral oophorectomy
b. Amenorrhea for 12 months or more
10. Known severe allergic reactions to the KE drinks or other ketogenic supplement or stevia products.
11. 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.
12. Very high or severe hypertriglyceridemia (>=886 mg/dL or 10.0 mmol/L)
13. Severe Hypertension (systolic blood pressure >=180 mmHg and/or diastolic blood pressure >=120 mmHg)
14. Weight >= 300 lbs (MRI scanner weight limit)
15. Diabetes Mellitus (type 1 or 2)
16. Taking the drug metformin.
17. Non-English speakers (given staffing constraints for cognitive testing administration and need for decreased variability in testing procedures for a small N study).
18. 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.
19. 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.
Principal Investigator
Referral Contact
For more information: