KNA Proof-of-Concept

Feasibility Trial Assessing Adherence and Response to a Ketogenic Dietary Intervention for Individuals at High Risk for Alzheimer's Disease

The intervention program proof-of-concept was assessed as a single-arm, within-subjects clinical study with a target enrollment of 10 participants with possible or probable amnestic MCI. The protocol required participants to complete a pre-intervention assessment within two weeks of beginning the intervention, attend seven, one-hour intervention group sessions across six weeks, complete a post-assessment and interview in the final week of the intervention, and complete weekly surveys throughout the intervention.

Study Overview

• Status: Completed
• Conditions: Adherence, Treatment; Retention; Cognitive Impairment, Mild
• Intervention / Treatment: Behavioral: Motivational Interviewing-Cognitive Behavioral Therapy Ketogenic Nutrition Adherence Program

Detailed Description

The primary goal of the proof-of-concept phase is to use pre-post comparisons to determine if the treatment package can produce clinically significant improvements. Thus, our goal was to assess whether the MI-CBT KNA program influenced adherence to KN and cognitive outcomes. Of note, recruitment for the trial occurred in the weeks leading up to the COVID-19 pandemic, which substantially altered the original intervention and assessment design due to restrictions on in-person human subject research. While the original protocol included in-person assessments and group meetings, collection of multiple biological samples (i.e., lipid panels, basic vitals, inflammatory biomarkers), and weekly health assessments, these in-person components were modified or removed for completion during the COVID-19 pandemic. Pre-assessment and screening appointments described below were completed in-person prior to the COVID-19 pandemic. Thus, we completed pre-intervention neuropsychological assessments with participants at baseline prior to beginning the trial; however, immediately following baseline assessments, we fully revised the protocol to include only online, video, and phone contact. We moved the KNA program to an online platform (HIPAA-compliant Zoom), and assessments were changed to online surveys and video assessments. Individual testing of the video platform was completed prior to the trial, which successfully reduced technical problems.

The MI-CBT KNA Program proof-of-concept was assessed as a single-arm, within-subjects clinical study with a target enrollment of 10 participants with possible or probable amnestic MCI. The protocol required participants to complete a pre-intervention assessment within two weeks of beginning the intervention, attend seven, one-hour intervention group sessions across six weeks, complete a post-assessment and interview in the final week of the intervention, and complete weekly surveys throughout the intervention. Participants were mailed materials, including the participant workbook and food, macronutrient, and ketone logs. Participants were also sent two bottles of ketone urine test strips for daily testing and materials to complete follow-up assessments. Throughout the program, participants were instructed to titrate into full ketosis across the first four weeks of the program by gradually reducing total carbohydrate intake and increasing healthy fat intake (e.g., fish, nuts, avocado, olive oils etc.). Thus, participants were not expected to attain measurable ketone levels until the final weeks of the program.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Florida
    • Tallahassee, Florida, United States, 32306
      • Florida State University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Final inclusion criteria included individuals who met criteria for "possible" Mild cognitive impairment (MCI), which was defined as the following: evidence of either subjective decline in memory and greater self-reported use of compensatory strategies OR poorer performance than expected in one or more cognitive domain OR limited evidence of impairment in both subjective and objective findings.

Exclusion Criteria:

• Presence of severe and/or unstable medical conditions
• diagnosable major neurocognitive disorder

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: MI-CBT KNA Program; 6-week group intervention using MI and CBT strategies to promote adherence to a ketogenic nutrition program.

Behavioral: Motivational Interviewing-Cognitive Behavioral Therapy Ketogenic Nutrition Adherence Program; The intervention using strategies from motivational interviewing and cognitive behavioral therapy to promote motivation and adherence to ketogenic nutrition in older adults at high risk for Alzheimer's disease. The program is a 6-week, group program led by a psychologist and nutrition expert.; Other Names: MI-CBT KNA Program

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Retention	Assessed based on attendance and % of participants who remained in the program from start to finish	baseline to 6-weeks
Ketogenic Adherence	Assessed based on reported ketone levels during the program (reporting at least one day or greater with trace amounts of ketones) using urinalysis ketone test strips administered at home by participants.	6-weeks
Acceptability	Assessed based on qualitative feedback and online surveys described here: https://pilotfeasibilitystudies.biomedcentral.com/articles/10.1186/s40814-022-00970-z. Participants also rated how well they felt the program helped them achieve their health-related goals 0 (none) to 3 (all).	6-weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive Functioning	Assessed using the total scaled score (age-normed) of the Repeatable Battery for the Assessment of Neuropsychological Status - Update. A score of 100 is considered "average" (50th percentile), and higher scores are considered better cognitive functioning. The outcome reported is the actual value at 6-weeks, rather than a change score.	Baseline and 6-weeks

Collaborators and Investigators

• Sponsor: Florida State University

Publications and helpful links

General Publications

• Sheffler JL, Arjmandi B, Quinn J, Hajcak G, Vied C, Akhavan N, Naar S. Feasibility of an MI-CBT ketogenic adherence program for older adults with mild cognitive impairment. Pilot Feasibility Stud. 2022 Jan 22;8(1):16. doi: 10.1186/s40814-022-00970-z.

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2019
• Primary Completion (Actual): June 30, 2020
• Study Completion (Actual): August 30, 2020

Study Registration Dates

• First Submitted: July 13, 2021
• First Submitted That Met QC Criteria: July 13, 2021
• First Posted (Actual): July 20, 2021

Study Record Updates

• Last Update Posted (Estimated): March 1, 2024
• Last Update Submitted That Met QC Criteria: August 1, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: STUDY00000111

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