BRain Energy Activation With Ketones to Prevent Alzheimer's Disease (BREAK-AD)

6 Month Randomized Controlled Trial With D-beta-hydroxybutyrate in Mild Cognitive Impairment

A six month randomized controlled intervention with an exogenous ketone salt (EKS) supplement in mild cognitive impairment. Participants will receive 15 g of the supplement twice daily (equivalent to 24 g/day of EKS). Outcomes: brain energy metabolism, cognition, plasma biomarkers, brain imaging (volumetric, functional, structural) and quality of life will be analyzed before and after the intervention.

Study Overview

• Status: Completed
• Conditions: MCI
• Intervention / Treatment: Dietary supplement: Active group; Dietary supplement: Placebo group

• Study Type: Interventional
• Enrollment (Actual): 65
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H4C4
      • Rearsh Centre on Aging

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• The participant must answer Yes to the question ''Do you think your memory is not as good as it was?''
• Have a MoCA Score between 20/30 and 26/30
• Have a QAF score of less than 9/30
• Understand, read and talk French
• Having good visual and hearing acuity

Exclusion Criteria:

• Major cognitive decline or neurodegenerative disease.
• Already consuming a daily medium chain triglyceride or ketone supplement.
• Soy, milk, gluten or allergy to the study product
• Controlled or uncontrolled diabetes
• Uncontrolled chronic disease
• Vitamin B12 deficit
• Clinical anomaly in the blood chemistry profile
• QSP-9 score over 19/27
• Taking an anti-cholinergic drugs
• Recent change in medication
• Active cancer in the last 2 years
• General anesthesia in the last 6 months
• history of alcohol abuse or dependence in the last 2 years
• Participation in other interventional or PET research project
• Unable to undergo an MRI or PET scan
• History of kidney stones or hypercalcemia
• History of cardiovascular events or insufficiency
• Renal failure and / or creatinine <58 umol or> 110 umol for men and <46 umol or> 92 umol for women or if the GFR (glomerular filtration rate) <60 ml / min / 1.73 m2
• Chronic disease of the digestive system or intestinal malabsorption (celiac disease, chronic pancreatitis, Crohn's disease, etc.)
• Body mass index <20 or voluntary weight loss of more than 5% in the last 6 months.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Active group; Participants will be on the active intervention for 6 months	Dietary supplement: Active group; 2 x 12 g of EKS/day
Placebo Comparator: Placebo Group; Participants will be on the placebo intervention for 6 months	Dietary supplement: Placebo group; Isocaloric placebo supplement with similar salt load but no EKS
Active Comparator: Open phase on active product; At the end of the 6-month randomized controlled phase, participants will be unblinded and invited to continue on the active product for an additional 3 months.	Dietary supplement: Active group; 2 x 12 g of EKS/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acetoacetate brain uptake	CMRacac measured by PET Scan	6 months
Glucose brain uptake	CMRgluc measured by PET Scan	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognition		0-3-6-9 months
Plasma biomarkers	glucose, fatty acids, ketones	9 months
Structural and functional brain measures		6 months

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Collaborators: Alzheimer's Association; Nestle Health Science

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2020
• Primary Completion (Actual): December 12, 2024
• Study Completion (Actual): March 10, 2025

Study Registration Dates

• First Submitted: July 7, 2020
• First Submitted That Met QC Criteria: July 9, 2020
• First Posted (Actual): July 10, 2020

Study Record Updates

• Last Update Posted (Actual): June 3, 2025
• Last Update Submitted That Met QC Criteria: May 28, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: 2020-3448

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No