Proof of Mechanism of a New Ketogenic Supplement Using Dual Tracer PET (Positron Emission Tomography)

NCT02551419 | Completed

• 1 other identifier: 2015-509
• Study Type: interventional
• Target: 82
• Locations: 1 country
• Sites: 1

Brief Summary

A six month, placebo-controlled, parallel group project in which MCI participants will receive 30 g/day of a custom-made MCT-based ketogenic supplement or a matching placebo. Uptake of both the brain's fuels - ketones (as 11C-AcAc) and glucose (as FDG) - both before and after the intervention will be assessed by PET (position emission tomography) ; imaging and ketone pharmacokinetic as primary objective as well as fMRI, diffusion MRI and cognition.

Conditions

Mild Cognitive Impairment

Keywords

mild cognitive impairment; ketones; medium chain triglycerides; Positron emission tomography; magnetic resonance imaging; cognition; brain; neuroimaging

Outcome Measures

Primary Outcomes (2)

• Change in global ketone (11C-AcAc) uptake in grey matter

  The change in brain ketone uptake will be quantified by PET and expressed as cerebral metabolic rate of AcAc (CMR-A)

  Baseline and 6 months of intervention

• Change in plasma ketone

  The change in plasma ketone will be measure to obtain a ketone chronic response

  Baseline and 6 months of intervention

Secondary Outcomes (12)

• Change in global brain FDG uptake in grey matter (CMR-G)

  Baseline and 6 months of intervention

• Change in regional CMR-A

  Baseline and 6 months of intervention

• regional brain volumes by vMRI

  Baseline and 6 months of intervention

• Change in cognitive status - episodic memory

  Baseline and 6 months of intervention

• Change in cognitive status- language domain

  Baseline and 6 months of intervention

Study Arms (2)

ketogenic drink

EXPERIMENTAL

MCT ketogenic drink: ketogenic drink providing 30 g/d of MCT oil in 250 ml of lactose-free skim milk for 6 months supplementation

Dietary Supplement: ketogenic drink

Placebo

PLACEBO COMPARATOR

Lactose-free skim milk-based placebo drink containing high-oleic sunflower oil of equivalent energy value to the active arm for a 6 months supplementation

Dietary Supplement: placebo

Interventions

ketogenic drink DIETARY_SUPPLEMENT

6 months' supplementation with the ketogenic drink . Product will be taken daily - 125 ml will be consumed at the morning meal, and 125 ml at the evening meal.

ketogenic drink

placebo DIETARY_SUPPLEMENT

6 months' supplementation with the placebo drink . Product will be taken daily - 125 ml will be consumed at the morning meal, and 125 ml at the

Placebo

Eligibility Criteria

• Age: 55 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• subjective memory complaint
• Montreal Cognitive Assessment (MoCA) score of 18-26/30 or a Mini-mental state exam (MMSE) score of 24-27/30
• autonomy for activity of daily living
• absence of depression

You may not qualify if:

• diagnosis of a major cognitive disorder
• diseases or psychiatric disorders that could interfere with participation
• uncontrolled diabetes (fasting plasma glucose \>7 mM or glycated hemoglobin \>6.5%)
• major depression or history of alcohol or substance abuse within the past 2 years,
• already supplementing with coconut oil or MCT
• vitamin B12 deficiency
• uncontrolled hypertension, dyslipidemia, or thyroid disease,
• visual or hearing impairment impeding comprehension
• participation in another intervention trial
• inability to lie down without moving for 60 min (for the brain imaging)
• presence of implanted metal objects or devices contraindicated for MRI (phase 1)

Sponsors & Collaborators

• Université de Sherbrooke: lead
• Alzheimer's Association: collaborator

Study Sites (1)

Research Center on Aging

Sherbrooke, Quebec, J1H 4C4, Canada

Location

Related Publications (5)

• Castellano CA, Nugent S, Paquet N, Tremblay S, Bocti C, Lacombe G, Imbeault H, Turcotte E, Fulop T, Cunnane SC. Lower brain 18F-fluorodeoxyglucose uptake but normal 11C-acetoacetate metabolism in mild Alzheimer's disease dementia. J Alzheimers Dis. 2015;43(4):1343-53. doi: 10.3233/JAD-141074.

  PMID: 25147107 BACKGROUND

• Nugent S, Castellano CA, Goffaux P, Whittingstall K, Lepage M, Paquet N, Bocti C, Fulop T, Cunnane SC. Glucose hypometabolism is highly localized, but lower cortical thickness and brain atrophy are widespread in cognitively normal older adults. Am J Physiol Endocrinol Metab. 2014 Jun 1;306(11):E1315-21. doi: 10.1152/ajpendo.00067.2014. Epub 2014 Apr 15.

  PMID: 24735889 BACKGROUND

• Nugent S, Tremblay S, Chen KW, Ayutyanont N, Roontiva A, Castellano CA, Fortier M, Roy M, Courchesne-Loyer A, Bocti C, Lepage M, Turcotte E, Fulop T, Reiman EM, Cunnane SC. Brain glucose and acetoacetate metabolism: a comparison of young and older adults. Neurobiol Aging. 2014 Jun;35(6):1386-95. doi: 10.1016/j.neurobiolaging.2013.11.027. Epub 2013 Dec 1.

  PMID: 24388785 BACKGROUND

• Courchesne-Loyer A, Fortier M, Tremblay-Mercier J, Chouinard-Watkins R, Roy M, Nugent S, Castellano CA, Cunnane SC. Stimulation of mild, sustained ketonemia by medium-chain triacylglycerols in healthy humans: estimated potential contribution to brain energy metabolism. Nutrition. 2013 Apr;29(4):635-40. doi: 10.1016/j.nut.2012.09.009. Epub 2012 Dec 28.

  PMID: 23274095 BACKGROUND

• Cunnane S, Nugent S, Roy M, Courchesne-Loyer A, Croteau E, Tremblay S, Castellano A, Pifferi F, Bocti C, Paquet N, Begdouri H, Bentourkia M, Turcotte E, Allard M, Barberger-Gateau P, Fulop T, Rapoport SI. Brain fuel metabolism, aging, and Alzheimer's disease. Nutrition. 2011 Jan;27(1):3-20. doi: 10.1016/j.nut.2010.07.021. Epub 2010 Oct 29.

  PMID: 21035308 BACKGROUND

MeSH Terms

Conditions

Cognitive Dysfunction; Ketosis

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Stephen Cunnane, Ph.D.

  Université de Sherbrooke

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 15, 2015
• First Posted: September 16, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2019
• Study Completion: December 1, 2019
• Last Updated: March 26, 2020

Record last verified: 2019-11

Locations

CA (1)