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

Mild Cognitive Impairment Clinical Trial

— BENEFIC  

Official title:

Effect of a Ketogenic Supplement on Brain Energy Metabolism Measured by Neuroimaging in Mild Cognitive Impairment

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02551419
• Other study ID #: 2015-509
• Status: Completed
• Phase: N/A
• Start date: June 2015
• Est. completion date: December 2019

Study information

• Verified date: November 2019
• Source: Université de Sherbrooke
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 82
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 55 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Mild Cognitive Impairment

Intervention

Dietary Supplement:
• ketogenic drink
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.
• placebo
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

Locations

Country	Name	City	State
Canada	Research Center on Aging	Sherbrooke	Quebec

Sponsors (2)

Lead Sponsor	Collaborator
Université de Sherbrooke	Alzheimer's Association

Country where clinical trial is conducted

Canada, 

References & Publications (5)

Castellano CA, Nugent S, Paquet N, Tremblay S, Bocti C, Lacombe G, Imbeault H, Turcotte É, 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. — View 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. — View 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. Review. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	Change in global brain FDG uptake in grey matter (CMR-G)	The change in brain glucose uptake will be quantified by PET and expressed as cerebral metabolic rate of glucose (CMR-G)	Baseline and 6 months of intervention
Secondary	Change in regional CMR-A	The change in brain ketone uptake will be quantified by PET in different regions of the brain	Baseline and 6 months of intervention
Secondary	regional brain volumes by vMRI	Change in brain volume measure by MRI	Baseline and 6 months of intervention
Secondary	Change in cognitive status - episodic memory	Change in episodic memory assessed by the 16-item free/cued word learning (Buschke and Grober test- Z score of trial 1, 2, 3 and delay) and the Brief Visuospatial Memory Test-revised (Z score of trial 1)	Baseline and 6 months of intervention
Secondary	Change in cognitive status- language domain	Change in language assessed by Boston Naming Test (Z score)	Baseline and 6 months of intervention
Secondary	Change in cognitive status - executive function	Change in executive function assessed by condition 4 of the trail making test, condition 3 and 4 of the Stroop test and the 4 conditions of verbal fluency test (all Z score)	Baseline and 6 months of intervention
Secondary	Change in cognitive status - processing speed	Change in processing speed assessed by global score of Digit Span (WAIS III), Digit Symbol (WAIS III), condition 1 and 2 of Stroop test and condition 1,2,3,5 of the trail making test (all Z score)	Baseline and 6 months of intervention
Secondary	Blood metabolite profile triglycerides	Changes in Triglycerides (mM)	Baseline and 6 months of intervention
Secondary	Blood metabolite profile Glucose	Changes in Glucose (mM)	Baseline and 6 months of intervention
Secondary	Blood metabolite profile cholesterol	Changes in Total cholesterol (mM)	Baseline and 6 months of intervention
Secondary	Derived cerebral metabolic rate of total ketones	Cerebral metabolic rate of total ketone derived from ketone PET (dCMRket, µmol/100 g/min)	Baseline and 6 months of intervention
Secondary	Pharmacokinetic ketone response (phase 2)	Area under the curve of pharmacokinetic of blood ketone	Baseline and 6 months of intervention