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| Name | Class |
|---|---|
| Alzheimer's Association | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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 |
|
| 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Change in regional CMR-A |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Stephen Cunnane, Ph.D. | Université de Sherbrooke | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Research Center on Aging | Sherbrooke | Quebec | J1H 4C4 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 25147107 | Background | 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. | |
| 24735889 | Background |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| SAP | No | Yes | No | Statistical Analysis Plan | Nov 28, 2019 | Nov 29, 2019 | SAP_000.pdf |
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| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D007662 | Ketosis |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D000138 | Acidosis |
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| 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 |
|
The change in brain ketone uptake will be quantified by PET in different regions of the brain
| Baseline and 6 months of intervention |
| regional brain volumes by vMRI | Change in brain volume measure by MRI | Baseline and 6 months of intervention |
| 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 |
| Change in cognitive status- language domain | Change in language assessed by Boston Naming Test (Z score) | Baseline and 6 months of intervention |
| 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 |
| 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 |
| Blood metabolite profile triglycerides | Changes in Triglycerides (mM) | Baseline and 6 months of intervention |
| Blood metabolite profile Glucose | Changes in Glucose (mM) | Baseline and 6 months of intervention |
| Blood metabolite profile cholesterol | Changes in Total cholesterol (mM) | Baseline and 6 months of intervention |
| 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 |
| Pharmacokinetic ketone response (phase 2) | Area under the curve of pharmacokinetic of blood ketone | Baseline and 6 months of intervention |
| 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. |
| 24388785 | 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. |
| 23274095 | 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. |
| 21035308 | 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. |
| D000137 |
| Acid-Base Imbalance |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |