Clinical trial NCT03472664: Brain Energy for Amyloid Transformation in Alzheimer's Disease Study
Official title: Brain Energy for Amyloid Transformation in AD (BEAT-AD) Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Alzheimer Disease
Mild Cognitive Impairment
Keywords: Memory
Diet
ketogenic
Lead sponsor: Wake Forest University Health Sciences
Sponsor class: OTHER
Collaborators: name: National Institute on Aging (NIA)
First posted: 2018-03-21
Enrollment: 120
Sex: ALL
Minimum age (years): 55
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Cerebrospinal Fluid (CSF) Abeta42
timeFrame: 16 Weeks
Secondary outcomes:
measure: CSF abeta42/ptau ratio
timeFrame: 16 Weeks
measure: Preclinical Alzheimer Cognitive Composite (PACC)
timeFrame: 16 Weeks
measure: Cerebral Blood Flow Measure with Arterial Spin Labeling (ASL) MRI
timeFrame: 16 Weeks
Other outcomes:
Locations:
city: Winston-Salem
country: United States
facility: Wake Forest Baptist Medical Center
state: North Carolina
Study officials:
affiliation: Wake Forest University Health Sciences
name: Suzanne Craft, PhD
role: PRINCIPAL_INVESTIGATOR
References: