ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03472664
Recruitment Status : Recruiting
First Posted : March 21, 2018
Last Update Posted : August 1, 2018
Sponsor:
Collaborator:
National Institute on Aging (NIA)
Information provided by (Responsible Party):
Wake Forest University Health Sciences

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.

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.


Condition or disease Intervention/treatment Phase
Alzheimer Disease Mild Cognitive Impairment Other: low carbohydrate/high fat diet Other: low fat/high carbohydrate diet Not Applicable

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  (Clinical Trial)
Estimated Enrollment : 120 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Adults with amnestic mild cognitive impairment will be randomized on a 1:1 schedule to receive either a 4-month Modified Mediterranean Ketogenic Diet or American Heart Association Diet 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. Amyloid positron emission tomography (PET) will be conducted at baseline. Blood collection and cognitive assessment will be conducted at baseline and after 2 and 4 months of diet. Lumbar puncture (LP) and MRI will be conducted at baseline and following the intervention for all participants.
Masking: Double (Investigator, Outcomes Assessor)
Masking Description:

It is not possible for participants and the dietitian to be blinded to the study diet.

Study personnel involved in performing cognitive testing or other outcome procedures or data analysis will be blinded.

Primary Purpose: Treatment
Official Title: Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study
Actual Study Start Date : July 16, 2018
Estimated Primary Completion Date : April 2023
Estimated Study Completion Date : April 2023


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.




Primary Outcome Measures :
  1. Cerebrospinal Fluid (CSF) Abeta42 [ Time Frame: 16 Weeks ]
    CSF Aβ42 is a a key AD biomarker that reflects pathological aggregation of amyloid in the brain.


Secondary Outcome Measures :
  1. CSF abeta42/ptau ratio [ Time Frame: 16 Weeks ]
    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.

  2. Preclinical Alzheimer Cognitive Composite (PACC) [ Time Frame: 16 Weeks ]

    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.


  3. Cerebral Blood Flow Measure with Arterial Spin Labeling (ASL) MRI [ Time Frame: 16 Weeks ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   55 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of amnestic mild cognitive impairment
  • An informant (study partner) able to accompany the participant to at least 3 visits, including at least two diet education visits
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03472664


Contacts
Contact: Ashley Sanderlin, PhD 336-713-8817 asanderl@wakehealth.edu

Locations
United States, North Carolina
Wake Forest Baptist Medical Center Recruiting
Winston-Salem, North Carolina, United States, 27157
Contact: Leslie Goordineer    336-713-8477    lgordine@wakehealth.edu   
Sponsors and Collaborators
Wake Forest University Health Sciences
National Institute on Aging (NIA)
Investigators
Principal Investigator: Suzanne Craft, PhD Wake Forest University Health Sciences

Responsible Party: Wake Forest University Health Sciences
ClinicalTrials.gov Identifier: NCT03472664     History of Changes
Other Study ID Numbers: IRB00049474
1R01AG055122-01 ( U.S. NIH Grant/Contract )
First Posted: March 21, 2018    Key Record Dates
Last Update Posted: August 1, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Data sharing will follow guidelines and timeline recommended by the National Institute on Aging.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Analytic Code
Time Frame: The data will become available one year after completion of the study and remain available indefinitely.
Access Criteria: Consultation with the study team to verify purpose of data sharing request, and collaborative involvement of study team if appropriate.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Wake Forest University Health Sciences:
Memory
Diet
ketogenic

Additional relevant MeSH terms:
Alzheimer Disease
Cognitive Dysfunction
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders