Dietary Ketosis: Fatty Acids Activate AMPK Energy Circuits Modulating Global Methylation

NCT03319173 | Completed Results

• 1 other identifier: Bristlecone-001
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

Brief Summary

The study explores whether selective memory complaints (SMC), mild cognitive impairment (MCI) and the comorbidity of Metabolic Syndrome symptomatic of peripheral and cerebral hypo-metabolism with corresponding epigenetic shifts in global DNA (deoxyribonucleic acid) methylation (away from nutrient availability and toward biosynthesis) are initiated by chronic metabolic inflexibility, over-activation of the mTOR (mammalian target of rapamycin) pathway, and the deregulation of neural oxidative phosphorylation.

Conditions

Mild Cognitive Impairment; Metabolic Syndrome

Keywords

Mild Cognitive Impairment; AMPK activation; DNA global hypo-methylation; Metabolic Syndrome; Ketogenic diet; SAM/SAH Index; S-adenosylmethionine (SAM); S-adenosylhomocysteine (SAH); Region-Specific hyper-methylation; mTOR kinase pathway; AMP/ATP ratio; Low Reduction Potential; High Reduction Potential; Delta G; Exergonic; Endergonic; Epigenetic Histone Modification; Montreal Cognitive Assessment (MoCA); Brief Visual Memory Test-Revised (BVMT-R); Rey Auditory Verbal Learning Task (RAVLT); HOMA-IR

Outcome Measures

Primary Outcomes (1)

• MoCA (Montreal Cognitive Assessment)

  Measures changes in cognitive function over time. Score: 30 points (maximum), 0 points (minimum). Score \>25 = normal cognitive function. Score 17-25 = mild cognitive impairment (MCI). Score \<17 = increased likelihood of Alzheimer's Disease or dementia.

  12 weeks

Secondary Outcomes (15)

• NMR Lipoprofile Particle Size - Small LDL-P

  12 weeks

• NMR Lipoprofile Particle Size - LP-IR Score (Lipoprotein Insulin Resistance) Ideal Range: <45

  12 weeks

• Fasting Triglycerides

  12 weeks

• Triglyceride/HDL Ratio

  12 weeks

• Fasting Insulin

  12-weeks

Study Arms (2)

Experimental group

EXPERIMENTAL

Dietary interventions for subjects in the experimental group include clinically regulated meal plans designed to facilitate prolonged benign dietary ketosis (BDK) in order to regulate glucose with restored insulin sensitivity focused at reversing the impaired capacity to switch between fat and carbohydrate oxidation. Subjects will consume 3 meals per day with the following approximate macronutrient breakdown per meal: 65% fat, 25% protein, 10% carbohydrate. Both groups will play the Advanced PEAK brain training games on iPhone, iPad or Android devices for 75 minutes per week.

Behavioral: Dietary intervention

Control group

ACTIVE COMPARATOR

Dietary interventions for subjects in the control group include the subjects' current dietary protocol (Standard American Diet-SAD). Subjects will consume 4-6 small meals per day with the following approximate macronutrient breakdown per meal: 50% carbohydrate, 35% protein, 15% fat. Both groups will play the Advanced PEAK brain training games on iPhone, iPad or Android devices for 75 minutes per week.

Behavioral: Dietary intervention

Interventions

Dietary intervention BEHAVIORAL

Subjects in the experimental group will receive clinically regulated meal plans designed to facilitate prolonged benign dietary ketosis (BDK) in order to regulate glucose with restored insulin sensitivity focused at reversing the impaired capacity to switch between fat and carbohydrate oxidation. Subjects in the control group will follow the their current dietary protocol (Standard American Diet-SAD).

Control group; Experimental group

Eligibility Criteria

• Age: 35 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or Female (age 35-80)
• Previously diagnosed with MetS and/or T2DM as measured by possessing at least two of the following physiological measures: type 2 diabetes, BMI \> 30, HgA1c \> 5.7%, waist/height ratio \> .6, fasting glucose \> 125 mg/dL
• Subjective Memory Complaints (SCM) - Subjects score \> 3 'yes' answers on the Subjective Memory Complaints Questionnaire
• Previously diagnosed with Mild Cognitive Impairment (MCI)

You may not qualify if:

• Previously diagnosed with Alzheimer's disease (AD), dementia or Parkinson's disease

Sponsors & Collaborators

• Bristlecone Health, Inc.: lead
• University of Minnesota: collaborator

Study Sites (1)

Bristlecone Health, Inc.

Maple Grove, Minnesota, 55311, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction; Metabolic Syndrome

Interventions

Diet Therapy

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Nutrition Therapy; Therapeutics

Limitations and Caveats

No limitations or caveats

Results Point of Contact

• Title: Dr. Kelly J. Gibas
• Organization: Bristlecone Health, Inc.

kelly-gibas@bethel.edu

763-913-4600

Study Officials

• Kelly J Gibas, Doctorate

  Bristlecone Health, Inc.

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: To assess differences between the control and experimental groups, a mixed model will be fit for each variable separately using both baseline (week 0) and post program (week 12) values for each subject. Models will include week, group, and their interaction as fixed effects, gender as a covariate, and subject as a random effect. To assess significant differences, we will use the difference at week 12 adjusted for the baseline difference, and will report p-values, least squares means, and 95% confidence intervals. Further analysis of treatment effects over time will be examined by comparing the within-group differences over time.

Study Record Dates

• First Submitted: October 14, 2017
• First Posted: October 24, 2017
• Study Start: October 15, 2017
• Primary Completion: September 30, 2018
• Study Completion: September 30, 2018
• Last Updated: November 12, 2019
• Results First Posted: November 12, 2019

Record last verified: 2019-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)