Proof of Mechanism of a New Ketogenic Supplement Using Dual Tracer PET (Positron Emission Tomography)
- Conditions
- Mild Cognitive Impairment
- Interventions
- Dietary Supplement: placeboDietary Supplement: ketogenic drink
- Registration Number
- NCT02551419
- Lead Sponsor
- Université de Sherbrooke
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 82
- 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
- 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)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo placebo 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 ketogenic drink ketogenic drink MCT ketogenic drink: ketogenic drink providing 30 g/d of MCT oil in 250 ml of lactose-free skim milk for 6 months supplementation
- Primary Outcome Measures
Name Time Method Change in plasma ketone Baseline and 6 months of intervention The change in plasma ketone will be measure to obtain a ketone chronic response
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)
- Secondary Outcome Measures
Name Time Method 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
Blood metabolite profile Glucose Baseline and 6 months of intervention Changes in Glucose (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
Change in cognitive status- language domain Baseline and 6 months of intervention Change in language assessed by Boston Naming Test (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)
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 - 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)
Blood metabolite profile triglycerides Baseline and 6 months of intervention Changes in Triglycerides (mM)
Blood metabolite profile cholesterol Baseline and 6 months of intervention Changes in Total cholesterol (mM)
Trial Locations
- Locations (1)
Research Center on Aging
🇨🇦Sherbrooke, Quebec, Canada