Brain Energy for Amyloid Transformation in Alzheimer's Disease Study (BEAT-AD)

Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study

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.

Group 2 will include volunteers who have mild cognitive impairment. This group will complete a 16-week low-fat diet study, with follow-up assessment 8 weeks after diet final completion. Study measures, clinic visits and phone sessions will occur 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.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease; Mild Cognitive Impairment
• Intervention / Treatment: Other: low carbohydrate/high fat diet; Other: low fat/high carbohydrate 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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Sarah Bohlman, MS; Phone Number: 336-716-7354; Email: sarabrow@wakehealth.edu

Study Locations

• United States
  • North Carolina
    • Winston-Salem, North Carolina, United States, 27157
      • Recruiting
      • Wake Forest Baptist Medical Center
      • Contact: Sarah Bohlman, MS; Phone Number: 336-716-7354; Email: sarabrow@wakehealth.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Other: low carbohydrate/high fat diet; Modified Mediterranean-Ketogenic Diet is a low carbohydrate/high fat diet.
Experimental: 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.	Other: low fat/high carbohydrate diet; American Heart Association Diet is a low fat/high carbohydrate diet.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrospinal Fluid (CSF) Abeta42	CSF Aβ42 is a a key AD biomarker that reflects pathological aggregation of amyloid in the brain.	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF abeta42/ptau ratio	The ratio of CSF Aβ42 to tau is a key AD biomarker that reflects an integrated value of amyloid and tau pathology in the brain.	16 Weeks
Preclinical Alzheimer Cognitive Composite (PACC)	The PACC consists of Free and Cued Selective Reminding Test - Total Recall, Logical Memory IIa - Delayed Paragraph Recall, Digit Symbol Substitution Test, MMSE - Total Score and Category Fluency. Although the PACC was designed for use with preclinical AD, it is reasonable to assume it will also be sensitive in aMCI, as all PACC components are frequently used in aMCI studies. According to PACC developer, Reisa Sperling, MD, it is a useful indicator of cognitive change in aMCI in the Harvard Aging Brain Study (personal communication). Further, we observed significant improvement in our cognitive test composite that includes 2 PACC components following the MMKD.	16 Weeks
Cerebral Blood Flow Measure with Arterial Spin Labeling (ASL) MRI	Cerebral blood flow will be measured with pseudo continuous ASL MRI, and voxel based analyses will be conducted to determine diet-induced changes and their relationship to cognitive and biomarker outcomes.	16 Weeks

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Anticipated): April 1, 2025
• Study Completion (Anticipated): April 1, 2026

Study Registration Dates

• First Submitted: March 12, 2018
• First Submitted That Met QC Criteria: March 20, 2018
• First Posted (Actual): March 21, 2018

Study Record Updates

• Last Update Posted (Estimate): May 5, 2023
• Last Update Submitted That Met QC Criteria: May 4, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Diet; Memory; ketogenic
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Cognition Disorders; Alzheimer Disease; Cognitive Dysfunction
• Other Study ID Numbers: IRB00049474; 1R01AG055122-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data sharing will follow guidelines and timeline recommended by the National Institute on Aging.
• IPD Sharing Time Frame: The data will become available one year after completion of the study and remain available indefinitely.
• IPD Sharing Access Criteria: Consultation with the study team to verify purpose of data sharing request, and collaborative involvement of study team if appropriate.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No