A phase 1B multiple ascending dose study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of a medium chain triglyceride supplement in Alzheimer’s disease
Bibliographic record
Abstract
Abstract Background Impaired brain glucose metabolism is a prominent and early feature across neurodegenerative disorders, including Alzheimer’s disease (AD). Elevating brain ketones to bypass this metabolic failure is an emerging therapeutic strategy, with promising results in AD and Mild Cognitive Impairment (MCI). The Medium Chain Triglyceride Intervention in AD (MINT‐AD) is a randomized, placebo‐controlled Phase 1b trial investigating the pharmacokinetics and pharmacodynamics of a ketogenic supplement in Alzheimer’s disease (AD). It also explores outcome measures to support the development of larger ketogenic trials for this disorder. Method Patients (n=32) with a clinical diagnosis of with mild‐moderate AD (MMSE 16‐26) were randomized at 4:1 to twice daily medium chain triglyceride drink (MCT – 60% C8, 40% C10) prepared as a 12% emulsion in lactose‐free milk, or placebo. A total of four dose groups were recruited, with doses ranging from 5 grams twice daily up to 25 grams twice daily, for a total of 18 days (including 8‐day drug titration). Primary outcome measures were safety, tolerability and pharmacodynamics effects of MCT supplementation on plasma ketones, and the pharmacokinetics of the MCT supplement. Exploratory outcome measures included N‐acetyl aspartate and glutamine/glutamate MR spectroscopy, functional resting brain connectivity, brain blood flow (arterial spin labeling), continuous actigraphy, ambulatory sleep EEG, and cognitive measures. Result A total of 30 participants (94%) completed the study, with 2 subjects discontinuing early. MCT supplement up to 25 grams twice daily was safe and well tolerated in patients with mild‐moderate AD. Peak plasma ketones was seen around 4 hours post MCT ingestion. Exploratory cognitive and imaging measures are currently being analyzed and will be presented. Conclusion Ketogenic MCT supplementation is safe and well tolerated in AD, with reasonably predictable pharmacokinetic and ketogenic properties. These data exploring a larger dose range should inform dose selection in future trials with MCT supplementation.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.003 |
| Insufficient payload (model declined to judge) | 0.005 | 0.001 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".