Therapeutic Diets in Alzheimer's Disease (TDAD)

By doing this study, researchers hope to learn how the ketogenic and Therapeutic Lifestyles Changes diets affect cognition in patients with Alzheimer's disease.

Study Overview

• Status: Recruiting
• Conditions: Alzheimer Disease
• Intervention / Treatment: Behavioral: Ketogenic Diet; Behavioral: Therapeutic Lifestyles Changes Diet

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Jessica Keller, MS; Phone Number: 913-588-5355; Email: kkali17@kumc.edu
• Study Contact Backup: Name: Matthew Taylor, PhD; Phone Number: 913-588-5363; Email: mtaylor3@kumc.edu

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Recruiting
      • Clinical and Translational Science Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 48 years to 88 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of AD by current McKhann et al. criteria
• CDR global score of 0.5 or 1
• Agreed cooperation from an appropriate study partner
• Speaks English as primary language
• Age 50 to 90
• No medication changes within the past 30 days

Exclusion Criteria:

• Resides in a nursing home or dementia special care unit, or cannot control diet
• A potentially confounding serious medical risk including insulin-requiring diabetes, cancer requiring chemotherapy or radiation within the past 5 years, or a recent cardiac event (i.e. heart attack, angioplasty, etc.)
• Participating in another clinical trial or using an investigational drug or therapy within 30 days of the Screening Visit
• A history of renal stones

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic Diet; Study partners will be instructed to assist participants in adherence to a 1:1 ketogenic diet (approximately 70% fat, <10% carbohydrate, and 20% protein as energy). The diet will encourage ≥4 servings of non-starchy vegetables and 1/2 cup of berries daily. Participants will be provided an emulsified medium chain triglyceride supplement with a target intake of 1-2 tablespoons per day and micronutrient supplements consisting of multivitamin, vitamin D, calcium, and phosphorus. After the 3-month ketogenic diet, participants will complete a 1-month washout period in which they halt adherence to the ketogenic diet and resume their normal diet.	Behavioral: Ketogenic Diet; Three-month 1:1 ketogenic diet intervention (approximately 70% fat, <10% carbohydrate, and 20% protein).
Active Comparator: Therapeutic Lifestyles Changes Diet; Study partners will be instructed to assist participants in adherence to the Therapeutic Lifestyles Changes diet. The diet consists of 20-35% fat, 50-60% carbohydrate, and ~15% protein as energy. Fat intake will comprise <7% saturated fat, ≤20% monounsaturated fat, and ≤10% polyunsaturated fat as total energy. Cholesterol consumption will be ≤200mg per day. Participants are encouraged to eat ≥2 servings of fruit and ≥5 servings of vegetables per day.	Behavioral: Therapeutic Lifestyles Changes Diet; Three-month diet intervention that is low in fat and cholesterol, high in fruits, vegetables, and whole grains, and moderate in protein.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cognitive performance on the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCog11)	Cognitive performance will be assessed by a psychometrician using the Alzheimer's Disease Assessment Scale Cognitive Subscale (ADASCog11). The ADAS-Cog is an Alzheimer's disease specific, multi-domain cognitive assessment scored from 0-70 points with higher scores indicating poorer cognitive performance.	Baseline, 12 Weeks
Change in cognitive performance on the Mini-Mental State Exam (MMSE)	Global cognitive performance will be assessed by a psychometrician using the Mini-Mental State Exam (MMSE). The MMSE is a brief cognitive questionnaire with a maximum score of 30 points where higher scores indicate better cognitive performance.	Baseline, 12 Weeks
Change in cognitive performance on the Logical Memory Test (LMT)	The Logical Memory, subtest of the WMS-R is a standardized assessment of narrative episodic memory. A short story is orally presented, and the examinee is asked to recall the story immediately.	Baseline, 12 Weeks
Change in cognitive performance by Stroop test	Reaction time and accuracy will be assessed by a psychometrician using the Stroop test.	Baseline, 12 Weeks
Change in Clinical Dementia Rating (CDR)	The Clinical Dementia Rating is a 5-point scale (CDR 0, 0.5, 1, 2, and 3) used to characterize six domains of cognitive and functional performance applicable to Alzheimer disease and related dementias. CDR 0 indicates no dementia and higher values indicate more severe dementia. The scores of all six domains are averaged to form a global CDR score. Change in score from baseline to 3 months will be assessed.	Baseline, 12 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in cerebral concentration of N-Acetylaspartate (NAA)	Concentration of cerebral N-Acetylaspartate is measured using magnetic resonance spectroscopy in a 3T clinical scanner.	Baseline, 12 Weeks
Change in blood platelet mitochondrial function	Cytochrome c oxidase activity of blood platelets will be determined as a pseudo first order-rate constant (sec-1/mg protein) by measuring the oxidation of reduced cytochrome c at 550 nm.	Baseline, 6 Weeks, 12 Weeks
Change in self-reported symptoms by study partner	Severity of symptoms will be measured via a self-reported symptoms questionnaire, answered by participant study partners.	Baseline, 6 Weeks, 12 Weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of days positive for urinary ketone production	Participants will measure and report daily urinary ketone status using Ketostix (Bayer, Germany).	Daily for 90 days (the length of the diet intervention)
Change in blood ketone levels induced by ketogenic diet	We will measure serum beta-hydroxybutyrate levels.	Baseline, 6 Weeks, 12 Weeks
Dietary intake characterization prior to and after ketogenic diet initiation	Changes in food and nutrient intake will be assessed by monthly 3-day food records completed by participant study partners.	Baseline, 6 Weeks, 12 Weeks

Collaborators and Investigators

• Sponsor: University of Kansas Medical Center
• Collaborators: National Institute on Aging (NIA)

Study record dates

Study Major Dates

• Study Start (Actual): October 29, 2019
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): November 30, 2024

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: February 28, 2019
• First Posted (Actual): March 4, 2019

Study Record Updates

• Last Update Posted (Actual): September 29, 2023
• Last Update Submitted That Met QC Criteria: September 27, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: STUDY00143457

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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