The purpose of this study is to determine safety, tolerability, and pharmacokinetics/dynamics of a ketogenic dietary supplement containing medium chain triglycerides (MCTs) in patients with Alzheimer disease (AD). Novel imaging and laboratory biomarkers in response to this intervention will also be explored. In addition, a sub-study was added to the UBC-approved protocol on November 29, 2016, prior to enrollment of the first FTD participant in April 2017. The FTD sub-study was designed as a pilot study to evaluate the safety and tolerability of MCT supplementation in participants with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
43
10 days supplementation with the MCT drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.
10 days supplementation with the placebo drink. Participants in dose group 1 will be assigned to 10 g per day, those in dose group 2 will be assigned 20 g per day, those in dose group 3 will be assigned 30 g per day, those in dose group 4 will be assigned 40 g per day, and those in dose group 5 will be assigned 50 g per day. The drink will be taken in the morning and evening. Participants will be enrolled 8 per group in ascending order.
Djavad Mowafaghian Centre for Brain Health
Vancouver, British Columbia, Canada
Number of participants with adverse events, serious adverse events
Time frame: From baseline to day 10 of intervention
Plasma ketone concentrations in response to ascending dose of MCT
Plasma ketone concentrations of betahydroxybutyrate (BHB) and acetoacetate (AcAc) will be measured in response to MCT dosing from 10-50 grams daily.
Time frame: Day 10 of intervention at 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, and 6 hours post MCT dose
Safety and tolerability of SCCF-3012
Incidence of treatment-emergent adverse events, serious adverse events, and laboratory parameter changes during 3 months of continuous SCCF-3012 dosing at 30 g/day (15 g BID) in participants with nonfluent/agrammatic variant primary progressive aphasia (nfvPPA). Adverse events tabulated by severity (mild/moderate/severe) and relatedness to study intervention (unlikely/possible/probable/likely). Tolerability assessed by the proportion of participants able to complete 3 months of continuous dosing at the target dose without intervention-related discontinuation.
Time frame: Baseline to Month 6
Pharmacodynamic ketone response
Plasma β-hydroxybutyrate (BHB) concentration in FTD-nfvPPA participants at pre-dose, 1 hour, and 4 hours following ingestion of the study drink, measured at the end of each 3-month phase. Primary pharmacodynamic endpoint is the 4-hour post-dose plasma BHB at the end of the MCT phase.
Time frame: Baseline, Month 3, Month 6 (each at pre-dose, 1 hour, and 4 hours post-dose)
Area under the plasma concentration versus time curve (AUC) of MCT
To determine the MCT plasma concentration at stated time points in response to MCT dosing from 10-50 grams daily.
Time frame: Day 10 of intervention at 0.5, 1, 1.5, 2, 3, 4, 4.5, 5, 5.5, and 6 hours post MCT dose
Change in language function (WAB-R Part 1)
For FTD-nfvPPA, Western Aphasia Battery-Revised Part I Aphasia Quotient (AQ; range 0-100, higher = better language function). Administered by a blinded examiner. Within-subject change analyzed as end-of-MCT-phase AQ minus end-of-placebo-phase AQ.
Time frame: Baseline, Month 3, Month 6
Change in global functional status (FTLD-CDR-SB)
Frontotemporal Lobar Degeneration Clinical Dementia Rating Sum of Boxes (FTLD-CDR-SB), extended from the standard CDR with language and behaviour modules. Range 0-24, with higher scores indicating greater impairment. Within-subject change analyzed as end-of-MCT-phase minus end-of-placebo-phase.
Time frame: Baseline, Month 3, Month 6
Global clinical impression of change (CGIC)
Clinician Global Impression of Change (7-point scale: 1 = very much improved to 7 = very much worse), rated by a study clinician blinded to treatment allocation. At each follow-up visit, rating reflects change relative to the immediately preceding assessment (3-month phase) and is attributable to the treatment received during that phase.
Time frame: Month 3, Month 6
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