Clinical trial NCT02551419: Proof of Mechanism of a New Ketogenic Supplement Using Dual Tracer PET (Positron Emission Tomography)
Official title: Effect of a Ketogenic Supplement on Brain Energy Metabolism Measured by Neuroimaging in Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mild Cognitive Impairment
Keywords: mild cognitive impairment
ketones
medium chain triglycerides
Positron emission tomography
magnetic resonance imaging
cognition
brain
neuroimaging
Lead sponsor: Université de Sherbrooke
Sponsor class: OTHER
Collaborators: name: Alzheimer's Association
First posted: 2015-09-16
Enrollment: 82
Sex: ALL
Minimum age (years): 55
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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)

Primary outcomes:
measure: Change in global ketone (11C-AcAc) uptake in grey matter
timeFrame: Baseline and 6 months of intervention
measure: Change in plasma ketone
timeFrame: Baseline and 6 months of intervention
Secondary outcomes:
measure: Change in global brain FDG uptake in grey matter (CMR-G)
timeFrame: Baseline and 6 months of intervention
measure: Change in regional CMR-A
timeFrame: Baseline and 6 months of intervention
measure: regional brain volumes by vMRI
timeFrame: Baseline and 6 months of intervention
measure: Change in cognitive status - episodic memory
timeFrame: Baseline and 6 months of intervention
measure: Change in cognitive status- language domain
timeFrame: Baseline and 6 months of intervention
measure: Change in cognitive status - executive function
timeFrame: Baseline and 6 months of intervention
measure: Change in cognitive status - processing speed
timeFrame: Baseline and 6 months of intervention
measure: Blood metabolite profile triglycerides
timeFrame: Baseline and 6 months of intervention
measure: Blood metabolite profile Glucose
timeFrame: Baseline and 6 months of intervention
measure: Blood metabolite profile cholesterol
timeFrame: Baseline and 6 months of intervention
measure: Derived cerebral metabolic rate of total ketones
timeFrame: Baseline and 6 months of intervention
measure: Pharmacokinetic ketone response (phase 2)
timeFrame: Baseline and 6 months of intervention
Other outcomes:
Locations:
city: Sherbrooke
country: Canada
facility: Research Center on Aging
state: Quebec
Study officials:
affiliation: Université de Sherbrooke
name: Stephen Cunnane, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.