COGNIFOOD-Changing the Carbohydrate/Fat-ratio to Prevent Cognitive Decline and Alzheimer Pathology: A Pilot Study

NCT06105320 | Recruiting DMC

• 1 other identifier: COGNIFOOD-Pilot
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

A 2-arm (sequence), 2-period, 2-treatments, single blinded (outcome assessor), randomized crossover-trial (12+12 weeks with immediate contrast) comparing a low-carbohydrate-high-fat diet (LCHF) with a high-carbohydrate-low-fat diet (HCLF) among individuals with prodromal Alzheimer's disease.

Conditions

Prodromal Alzheimer's Disease; Alzheimer Disease; Mild Cognitive Impairment; Neurocognitive Disorders

Keywords

Cognitive health; Cognition; Dementia prevention; Macronutrients

Outcome Measures

Primary Outcomes (3)

• Recruitment Rate

  Number of participants that are randomized within 1 year from start of recruitment, or time to reach 40 randomized participants if reached within \<1 year.

  1 year from recruitment start

• Adherence

  Self-reported carbohydrate/fat-ratio (CFr) from 7-day food record: Intra-individual difference in CFr (log-transformed) between the diet treatments (mean Period 1 \[week 6 \&12\] vs. mean Period 2 \[week 18 \& 24\], reversed by arm) expressed as standard deviations of the baseline distribution.

  Week 0, 6, 12, 18, 24

• Retention Rate

  The proportion of those randomized who complete the 12-week and 24-week follow-up with data on both a. Self-reported carbohydrate/fat-ratio; b. Secondary outcomes

  Until the end of data collection

Secondary Outcomes (5)

• Global Cognition

  Week 0, 12, 24

• Amyloid β-42/40

  Week 0, 6, 12, 18, 24; Primary comparison: ∆0-12 weeks (w) vs. ∆0-24 w, reversed by arm.

• Phospho-Tau (pTau) 181/231/217

  Week 0, 6, 12, 18, 24; Primary comparison: ∆0-12 w vs. ∆0-24 w, reversed by arm.

• Neurofilament Light (NFL)

  Week 0, 6, 12, 18, 24; Primary comparison: ∆0-12 w vs. ∆0-24 w, reversed by arm.

• Glial Fibrillary Acidic Protein (GFAP)

  Week 0, 6, 12, 18, 24; Primary comparison: ∆0-12 w vs. ∆0-24 w, reversed by arm.

Other Outcomes (23)

• Continuous Glucose Monitoring (CGM)

  Week 0, 6, 12, 18, 24; Seven days at each timepoint.

• Food Record

  Week 0, 6, 12, 18, 24

• Body-Mass Index (BMI)

  Week 0, 6, 12, 18, 24

Study Arms (2)

1: LCHF-HCLF

ACTIVE COMPARATOR

LCHF (12 weeks) followed by HCLF (12 weeks) with immediate contrast (no "wash-out" period)

Other: LCHF; Other: HCLF

2: HCLF-LCHF

ACTIVE COMPARATOR

HCLF (12 weeks) followed by LCHF (12 weeks) with immediate contrast (no "wash-out" period)

Other: LCHF; Other: HCLF

Interventions

LCHF OTHER

A diet intervention with the following macronutrient targets: Carbohydrates: 10-25 E%; Fat 50-70 E%; Protein: 20-25 E%; Alcohol 0-5 E%

Also known as: Non-ketogenic carbohydrate restriction

1: LCHF-HCLF; 2: HCLF-LCHF

HCLF OTHER

A diet intervention with the following macronutrient targets: Carbohydrates: 50-60 E%; Fat 25-30 E%; Protein: 15-20 E%; Alcohol 0-5 E%

Also known as: A fat-restricted diet compatible with official dietary guidelines

1: LCHF-HCLF; 2: HCLF-LCHF

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Ability to fully understand written and verbal information regarding the study and provide signed and dated informed consent
• Prodromal Alzheimer's disease, as defined by Mild Neurocognitive Disorder due to Alzheimer's disease (AD) according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) criteria, and evidence for underlying AD pathology by either:
• Cerebrospinal fluid (CSF) β-amyloid 1-42/1-40x10 ratio \< 1 and/or total tau and/or phospho-tau and/or β-amyloid 42 based on local cut-offs OR
• Magnetic Resonance Imaging (MRI) evidence for medial temporal lobe atrophy (MTA score 1 or higher \[mesiotemporal atrophy\]) OR
• Abnormal Fludeoxyglucose F18 (FDG) Positron Imaging Tomography (PET) and/or Pittsburgh Compound-B (PiB) PET compatible with AD type changes.
• (When the diagnosis prodromal AD is confirmed from medical record, no cognitive testing or renewed assessment of biological AD-pathology is needed for fulfilling this criterion.)
• Montreal Cognitive Assessment (MoCa) ≥20.
• Availability of a study partner with sufficient contact with the participant, willing and able to give follow-up information on the participant as well as supporting the participant throughout the study.
• Self-reported expected motivation and ability to prepare most weakly meals according to given instructions, with support from the study partner.
• Accept plant-based food, plus food from at least one of the following categories: A. Fish; B. Meat; C. Eggs and dairy
• Ability to reliably undergo a cognitive test in Swedish

You may not qualify if:

• Major Neurocognitive Disorder (dementia) according to DSM-5
• Body-mass Index (BMI) \< 18 or BMI \> 35
• Diagnosed Diabetes Mellitus.
• Ongoing treatment with Metformin, Glucagon-Like Peptide 1 (GLP-1)-analog, or Sodium-Glucose Transport Protein 2 (SGLT-2)-inhibitors
• Diagnosed Familial Hypercholesterolemia
• Untreated or unstable Hypertension
• Alcohol or Substance abuse (current or within 2 years)
• A concomitant serious disease (e.g., cancer, or major psychiatric disorder or other neurological disorder than AD) as judged by study physician
• Major depression or Suicidal ideations (current or within 2 years)
• History of Stroke or Myocardial infarction during the last 5 years.
• Subjects with brain MRI (or CT) scan clinically significant infarct, intracranial macro bleeding, mass lesion or Normal Pressure Hydrocephalus. Those subjects with an MRI scan demonstrating minimal white matter changes (Fazekas scale for white matter lesions classification of 2 or below) and up to 2 lacunar infarcts which are judged to be clinically insignificant are allowed.
• Severe loss of vision or communicative ability
• Conditions preventing cooperation as judged by the study physician.
• Participation in any other intervention trial within 30 days (or, if applicable, 5 half-lives of the relevant drug if longer) before baseline and along the study period.
• Deviations from habitual diet within 1 month before study start. A carbohydrate-restricted or fat-restricted diet, as well as any time-restricted eating, is accepted as habitual diet if stable (and the participant is open to change).

Sponsors & Collaborators

• Karolinska University Hospital: lead
• Fingers Brain Health Institute: collaborator
• Karolinska Institutet: collaborator
• af Jochnick Foundation: collaborator

Study Sites (1)

Karolinska University Hospital

Solna, Sweden

RECRUITING

Related Publications (2)

• Norgren J, Sindi S, Sandebring-Matton A, Ngandu T, Kivipelto M, Kareholt I. The Dietary Carbohydrate/Fat-Ratio and Cognitive Performance: Panel Analyses in Older Adults at Risk for Dementia. Curr Dev Nutr. 2023 May 7;7(6):100096. doi: 10.1016/j.cdnut.2023.100096. eCollection 2023 Jun.

  PMID: 37275847 BACKGROUND

• Norgren J, Sindi S, Matton A, Kivipelto M, Kareholt I. APOE-Genotype and Insulin Modulate Estimated Effect of Dietary Macronutrients on Cognitive Performance: Panel Analyses in Nondiabetic Older Adults at Risk of Dementia. J Nutr. 2023 Dec;153(12):3506-3520. doi: 10.1016/j.tjnut.2023.09.016. Epub 2023 Sep 29.

  PMID: 37778510 BACKGROUND

MeSH Terms

Conditions

Alzheimer Disease; Cognitive Dysfunction; Neurocognitive Disorders

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Mental Disorders; Cognition Disorders

Study Officials

• Anne Börjesson-Hanson, MD, PhD

  Karolinska University Hospital

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anne Börjesson-Hanson, MD, PhD

CONTACT

+46-8-123 858 68; anne.borjesson-hanson@regionstockholm.se

Jakob Norgren, PhD

CONTACT

jakob.norgren@ki.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Assessors of disease monitoring outcomes (defined as Secondary outcomes below) are blinded. One of the primary outcomes (Adherence) assessed by dietitian which cannot be blinded.
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Head of Clinical Trials

Study Record Dates

• First Submitted: October 16, 2023
• First Posted: October 27, 2023
• Study Start: October 1, 2023
• Primary Completion: October 1, 2025
• Study Completion: April 1, 2026
• Last Updated: October 27, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)