Brain Energy for Amyloid Transformation in Alzheimer's Disease Study

NCT ID: NCT03472664

Last Updated: 2025-07-28

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-07-16
• Study Completion Date: 2026-04-30

Brief Summary

The Brain Energy for Amyloid Transformation in AD (Alzheimer's disease) or BEAT-AD study will compare the effects of a ketogenic low-carbohydrate diet and a low-fat diet in adults with mild cognitive impairment. The data collected will help determine whether diet interventions induce changes in cognitive function, cerebral blood flow, and levels of certain proteins and hormones in body fluids.

The study will include volunteers who have mild cognitive impairment, who will be randomly assigned to receive either a ketogenic low-carbohydrate diet or a low-fat diet for 16-weeks, with follow-up assessment 8 weeks after diet completion. Study measures, clinic visits and phone sessions will occur at baseline and throughout the 24-week study.

Participant will follow either a low-carbohydrate or low-fat diet that will be individually planned with help from a study dietitian. After completing the study diet for 16 weeks, participants will resume their normal diet. The final visits will occur at week 24 (8 weeks after the completing the diet). At the end of the 24-week study, participants will be given the opportunity to meet with the study dietitian for education and assistance with planning a healthy diet.

Detailed Description

This study will examine the effects of a 4-month Modified Mediterranean-Ketogenic Diet compared with an American Heart Association Diet (AHAD - a regimen that has been shown to reduce the risk for cardiovascular disease). We will investigate diet effects on AD biomarkers, on cognition, and on neuroimaging measures of blood flow. Our study will extend previous findings in several important ways by: 1) using a Modified Mediterranean-Ketogenic Diet rather than a traditional Ketogenic Diet, which has the potential for greater long-term compliance and health benefits; 2) increasing the sample size and duration of the diet intervention; 3) examining potential mechanisms of diet effects that may result in new biomarkers and therapeutic targets; and 4) examining key treatment response variables such as Apolipoprotein E (ApoE) genotype, amyloid positivity and metabolic status that could inform precision medicine approaches to dietary prescription.

Adults with amnestic mild cognitive impairment (MCI) will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean-Ketogenic Diet (MMKD) or American Heart Association Diet (AHAD) intervention. Diet interventions will be equicaloric with participants' normal diets. Personalized nutritional guidance and menus will be provided, and compliance will be assessed by a registered dietitian. The principal investigator will be responsible for the overall monitoring of the data and safety of study participants, with assistance by members of the study staff, and the Data and Safety Monitoring Board (DSMB), which will be responsible for monitoring the safety of research participants.

Conditions

Alzheimer Disease; Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Modified Mediterranean Ketogenic Diet

The MMKD is a low carbohydrate/high fat diet aimed at inducing ketosis, as the experimental diet in the proposed study. Participants on the MMKD will keep their daily carbohydrate consumption below 20 grams per day throughout the 4 month intervention.The MMKD group will be supplied with extra virgin olive oil during their in person visits to use as a source of fat in their diet, and will be encouraged to eat plentiful fish, lean meats, and nutrient rich foods that meet the requirement of <20 grams total carbohydrates per day.

Participants will receive a daily multivitamin (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.

Group Type: EXPERIMENTAL

low carbohydrate/high fat diet

Intervention Type: OTHER

Modified Mediterranean-Ketogenic Diet is a low carbohydrate/high fat diet.

American Heart Association Diet

The American Heart Association Diet (AHAD), is a low fat/high carbohydrate diet (\<40 grams/day) will be used as the control diet. Participants on the AHAD will be encouraged to limit their amount of fat intake to \<40 grams/day, while eating plentiful fruits, vegetables, and carbohydrates containing adequate fiber. Participants will receive the same daily multivitamin supplement (Centrum Silver) over the course of the study and instructed to take 1 tablet each day while on the diet.

Group Type: EXPERIMENTAL

low fat/high carbohydrate diet

Intervention Type: OTHER

American Heart Association Diet is a low fat/high carbohydrate diet.

Interventions

low carbohydrate/high fat diet

Modified Mediterranean-Ketogenic Diet is a low carbohydrate/high fat diet.

Intervention Type: OTHER

low fat/high carbohydrate diet

American Heart Association Diet is a low fat/high carbohydrate diet.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Diagnosis of amnestic mild cognitive impairment
• An informant (study partner) able to provide collateral information on the participant
• Stable medical condition (generally 3 months prior to screening visit) at the discretion of study physician
• Stable on medications (generally 4 weeks prior to screening visit) at the discretion of study physician
• Able to complete baseline assessments

Exclusion Criteria

• Diagnosis of neurodegenerative illness (except for MCI);
• History of a clinically significant stroke
• 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
• Sensory impairment (i.e.: visual or auditory) that would preclude the participant from participating in the protocol
• Diabetes that requires current use of diabetes medications
• Clinically significant elevations in liver function tests
• Active neoplastic disease (stable prostate cancer and non-melanoma skin cancer is permissible)
• History of epilepsy or seizure within past year
• Contraindications for MRI (claustrophobia, craniofacial metal implants, pacemakers)
• Significant medical illness or organ failure, such as uncontrolled hypertension or cardiovascular disease, chronic obstructive pulmonary disease, liver disease, or kidney disease

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

Wake Forest University Health Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Suzanne Craft, PhD

Role: PRINCIPAL_INVESTIGATOR

Wake Forest University Health Sciences

Locations

Wake Forest Baptist Medical Center

Winston-Salem, North Carolina, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Karen Gagnon

Role: CONTACT

Karen.Gagnon@Advocatehealth.org

(336) 713-8010

Lauren Latham

Role: CONTACT

lauren.latham@advocatehealth.org

(336) 716-6317

Facility Contacts

Amy Hughes, AAS

Role: primary

aehughes@wakehealth.edu

336-716-8634

Other Identifiers

1R01AG055122-01

Identifier Type: NIH

Identifier Source: secondary_id

View Link

IRB00049474

Identifier Type: -

Identifier Source: org_study_id