The Ketogenic Diet for Alzheimer's Disease

NCT04701957 | Recruiting

• 1 other identifier: APHP201281
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

The ketogenic diet (KD) is a metabolic shift, which stimulates the liver oxidation of fatty acids to produce ketone bodies. These ketone bodies represent an alternative fuel source for the brain. The benefits of KD in epilepsia have been demonstrated for decades. This diet may also provide benefits in Alzheimer's disease (AD) where neuronal glucose utilization declines from the early stage. Besides, the KD could decrease neuroinflammation, oxidative stress and enhance mitochondrial biogenesis. In murin models of AD, KD or Medium Chain Triglycerides consumption were associated with lower neuroinflammation but also with a diminution of neuropathologic features of AD (amyloid and tau lesions in the brain). Moreover, behavioural effets and improvements in memory and motor function have been highlighted. In humans, recent studies suggest cognitive benefits (memory, executive function) in AD, including in the Mild Cognitive Impairment (MCI) stage. The feasibility and the adherence to the diet proved to be correct, in small samples, in particular in MCI individuals over a short follow-up period (3 to 6 months). This study aims at examining the feasibility of a KD followed-up for one year in participants with early AD (N=70). Change in brain metabolism will be assessed using PET scan after 12 months, comparing KD with control diet. The effects on cognition, quality of life and daily living functioning will be analysed. The safety, nutritional changes and adhesion to the diet will be monitored throughout the study.

Conditions

Alzheimer Disease, Early Onset

Outcome Measures

Primary Outcomes (1)

• Feasibilty of Ketogenic diet with urinary ketone levels

  To assess the feasibilty of a KD, in patients affected by early AD followed for a period of 12 months, measuring urinary ketone levels.

  12 months

Secondary Outcomes (6)

• Efficiency of ketogenic diet on cognition

  12 months

• Safety of ketogenic diet with weight

  12 months

• Safety of ketogenic diet with albumin levels

  12 months

• Safety of ketogenic diet with lipid levels

  12 months

• Efficiency of ketogenic diet on brain metabolism

  12 months

Other Outcomes (2)

• Efficiency of ketogenic diet on Instrumental Activities of Daily Living performance

  12 months

• Efficiency of ketogenic diet on Quality of Life

  12 months

Study Arms (2)

Modified Atkins 2 :1 Ketogenic diet

EXPERIMENTAL

The Atkins 2: 1 diet as prescribed for the participants of our intervention group (N = 35) is based on a diet moderately rich in protein (meat, fish, cheese, eggs, vegetable proteins) and without restriction of fats, provided they are balanced, but limiting the carbohydrate intake (bread, pasta, rice) to 50 grams / day. The ratio calories from fat / calories from protein + carbohydrates will be 3 to 1

Behavioral: Ketogenic diet

Control diet

NO INTERVENTION

Interventions

Ketogenic diet BEHAVIORAL

The Atkins 2: 1 diet as prescribed for the participants of our intervention group (N = 35) is based on a diet moderately rich in protein (meat, fish, cheese, eggs, vegetable proteins) and without restriction of fats, provided they are balanced, but limiting the carbohydrate intake (bread, pasta, rice) to 50 grams / day. The ratio calories from fat / calories from protein + carbohydrates will be 3 to 1

Modified Atkins 2 :1 Ketogenic diet

Eligibility Criteria

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

You may qualify if:

• Age \>= 50
• AD confirmed by biomarkers (CSF and/or PET scan)
• CDR score=0.5 or 1
• Speaking/understanding French
• Presence of a caregiver

You may not qualify if:

• Diabetes
• Other neurological disease
• Chronic inflammatory disease or anti-inflammatory medication (e.g. NSAI, corticosteroids)
• Uncontrolled dyslipidemia
• Malnutrition (BMI \< 18; or weight loss \> 5% in 1 month or 10% in 6 months; or MNA \< 17)
• Severe chronic condition or organ dysfunction

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead
• France Alzheimer: collaborator

Study Sites (1)

Cognitive Neurology Center - Lariboisière Fernand Widal University Hospital (APHP)

Paris, 75010, France

RECRUITING

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Diet, Ketogenic

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Diet, Carbohydrate-Restricted; Diet Therapy; Nutrition Therapy; Therapeutics; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Central Study Contacts

LILAMAND Matthieu, MD PhD

CONTACT

+33140054954; matthieu.lilamand@aphp.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: recruitment : open medical follow-up : masked dietitians : open
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2020
• First Posted: January 8, 2021
• Study Start: March 30, 2023
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): March 1, 2027
• Last Updated: November 20, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)