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

Conditions

Mild Cognitive Impairment

Keywords

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

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.

Stephen C. Cunnane

Alzheimer s & Dementia2022-12-01

10.1002/alz.059627

Multimodal strategy to rescue the brain in mild cognitive impairment: Ketogenic oral nutrition supplementation with B vitamins and aerobic exercise

Stephen C. Cunnane, Russell H. Swerdlow, Marco Inzitari, Gloria Olaso‐Gonzalez, José Viña

European Journal of Clinical Investigation2022-04-307 citations

10.1111/eci.13806

Ketones and improved cognition in MCI: Links to ApoE and white matter energetics

Stephen C. Cunnane, Maggie Roy, François Rheault, Mélanie Fortier, Maxime Descoteaux et al. (9 authors)

Alzheimer s & Dementia2021-12-01

10.1002/alz.055678

Improved brain energetics and cognition after a 6‐month ketogenic intervention in mild cognitive impairment: Final results of the Benefic Trial

Stephen C. Cunnane, Mélanie Fortier, Christian‐Alexandre Castellano, Valerie St. Pierre, Marie‐Christine Morin et al. (10 authors)

Alzheimer s & Dementia2020-12-01

10.1002/alz.037961

[F3–04–04]: BRAIN KETONE PET AND COGNITIVE OUTCOMES AFTER A 6‐MONTH KETOGENIC INTERVENTION IN MCI

Stephen C. Cunnane

Alzheimer s & Dementia2017-07-01

10.1016/j.jalz.2017.07.277

Interventions

DIETARY_SUPPLEMENTketogenic 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.

DIETARY_SUPPLEMENTplacebo

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

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

BASIC_SCIENCE

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

55 Years to No maximum

Healthy volunteers

No

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)

Design outcomes

Primary

Measure	Time frame	Description
Change in global ketone (11C-AcAc) uptake in grey matter	Baseline and 6 months of intervention	The change in brain ketone uptake will be quantified by PET and expressed as cerebral metabolic rate of AcAc (CMR-A)
Change in plasma ketone	Baseline and 6 months of intervention	The change in plasma ketone will be measure to obtain a ketone chronic response

Secondary

Measure	Time frame	Description
regional brain volumes by vMRI	Baseline and 6 months of intervention	Change in brain volume measure by MRI
Change in cognitive status - episodic memory	Baseline and 6 months of intervention	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)
Change in cognitive status- language domain	Baseline and 6 months of intervention	Change in language assessed by Boston Naming Test (Z score)
Change in cognitive status - executive function	Baseline and 6 months of intervention	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)
Change in cognitive status - processing speed	Baseline and 6 months of intervention	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)
Change in global brain FDG uptake in grey matter (CMR-G)	Baseline and 6 months of intervention	The change in brain glucose uptake will be quantified by PET and expressed as cerebral metabolic rate of glucose (CMR-G)
Blood metabolite profile Glucose	Baseline and 6 months of intervention	Changes in Glucose (mM)
Blood metabolite profile cholesterol	Baseline and 6 months of intervention	Changes in Total cholesterol (mM)
Derived cerebral metabolic rate of total ketones	Baseline and 6 months of intervention	Cerebral metabolic rate of total ketone derived from ketone PET (dCMRket, μmol/100 g/min)
Pharmacokinetic ketone response (phase 2)	Baseline and 6 months of intervention	Area under the curve of pharmacokinetic of blood ketone
Blood metabolite profile triglycerides	Baseline and 6 months of intervention	Changes in Triglycerides (mM)
Change in regional CMR-A	Baseline and 6 months of intervention	The change in brain ketone uptake will be quantified by PET in different regions of the brain

Countries

Canada

Outcome results

None listed