Clinical trial NCT02984540: Effect of a Modified Ketogenic-Mediterranean Diet on Alzheimer's Disease
Official title: Effect of a Modified Ketogenic-Mediterranean Diet on Alzheimer's Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Insulin Resistance
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
First posted: 2016-12-07
Enrollment: 25
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: The purpose of the BEAM study is to compare the effects of a low-carbohydrate diet and a lowfat diet for adults with mild memory loss and adults with pre-diabetes. The data collected will help determine changes in cognitive function, brain structure and function, and levels of certain proteins and hormones in body fluids.

Detailed description: Participants will be enrolled into 1 of 3 study groups. Group 1 will include healthy volunteers with no apparent memory problems, memory complaints or family history of Alzheimer's disease or dementia. This group will complete cognitive assessments, blood and stool sample collection, neuroimaging, and lumbar puncture at week 0 only. Group 1 will NOT take part in the diet study.

Group 2 will have pre-diabetes, but no apparent memory problems that can be observed during cognitive testing. Group 2 will complete an 18-week diet study, with follow-up assessment 6 weeks after final diet completion. Throughout the study the following will also be completed; cognitive assessments, blood and stool sample collection, neuroimaging, and lumbar puncture.

Group 3 will have mild memory problems that are observed during cognitive testing. Group 3 will complete an 18-week diet study, with follow-up assessment 6 weeks after diet final completion. Throughout the study the following will also be completed; cognitive assessments, blood and stool sample collection, neuroimaging, and lumbar puncture.

Eligibility criteria: Inclusion Criteria:

1. Male or post-menopausal female;
2. Age 50 to 85 years inclusive;
3. Cognitive diagnosis ranged from cognitively normal for "'Healthy' and 'At-Risk'" to mild/moderate cognitive impairment for "MCI/eAD;"
4. Stable medical condition (generally 3 months prior to screening visit) at the discretion of study physician;
5. Stable on medications (generally 4 weeks prior to screening visit) at the discretion of study physician;
6. Able to complete baseline assessments;
7. HbA1c and fasting glucose within the normal (Healthy or MCI/eAD) or pre-diabetic (At-Risk or MCI/eAD) range depending on group.

Exclusion Criteria:

1. Diagnosis of neurodegenerative illness (except for MCI or early AD in the MCI/eAD group);
2. History of a clinically significant stroke;
3. Current evidence or history in past year of focal brain lesion, head injury with loss of consciousness or DSM-IV criteria for any major psychiatric disorder including psychosis, major depression, bipolar disorder, alcohol or substance abuse;
4. Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol;
5. Diabetes that requires current use of diabetes medications;
6. Current use of cholesterol/lipid lowering medications;
7. Clinically significant elevations in liver function tests;
8. Active neoplastic disease (stable prostate cancer and non-melanoma skin cancer is permissible);
9. History of epilepsy or seizure within past year;
10. Contraindications for MRI (claustrophobia, craniofacial metal implants, pacemakers);
11. Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease;
12. Use of the following medications: anticonvulsants, drugs with potential interfering CNS effects (other than cholinesterase inhibitors or memantine), medications with significant anticholinergic activity, anti-parkinsonian medications or regular use of narcotic analgesics;
13. If female, menstruation in the past 12 months or hysterectomy and current hormone replacement therapy medication;
14. Major digestive disorders, absorption issues, or surgeries that may be exacerbated by diet changes;
15. Untreated hypothyroidism or B12 deficiency;
16. Participants currently using resveratrol, CoQ10 (coenzyme Q10), coconut oil/other medium chain triglyceride-containing (ie: Axona) supplements, or curcumin will be excluded unless they are willing to discontinue them 2 weeks prior to the start of baseline visits and remain off for study duration.

Primary outcomes:
measure: Change in spinal fluid levels of biomarkers associated with Alzheimer's disease
timeFrame: Baseline CSF measures will be compared to measures obtained six weeks after the initiation of the ketogenic diet and six weeks after initiation of the American Heart Association Diet
Secondary outcomes:
measure: Change in memory composite score
timeFrame: Baseline cognitive measures will be compared to measures obtained six weeks after the initiation of the ketogenic diet and six weeks after initiation of the American Heart Association Diet
measure: Change in insulin sensitivity
timeFrame: Baseline metabolic measures will be compared to measures obtained six weeks after the initiation of the ketogenic diet and six weeks after initiation of the American Heart Association Diet
measure: change in 11C acetoacetate PET uptake
timeFrame: Baseline acetoacetate uptake will be compared to measures obtained six weeks after the initiation of the ketogenic diet and six weeks after initiation of the American Heart Association Diet
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Health
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Brinkley TE, Leng I, Register TC, Neth BJ, Zetterberg H, Blennow K, Craft S. Changes in Adiposity and Cerebrospinal Fluid Biomarkers Following a Modified Mediterranean Ketogenic Diet in Older Adults at Risk for Alzheimer's Disease. Front Neurosci. 2022 Jun 2;16:906539. doi: 10.3389/fnins.2022.906539. eCollection 2022.