HOPE4MCI trial: First trial targeting reduction of hippocampal overactivity to treat mild cognitive impairment due to Alzheimer’s disease with AGB101
Bibliographic record
Abstract
Abstract Background Evidence from preclinical models and human patients demonstrates that neuronal circuits become hyperactive in prodromal AD contributing to the accumulation of Alzheimer’s pathology and subsequent cognitive decline. Such data support the hypothesis that neural overactivity in the medial temporal lobe/hippocampus is a critical driver of AD neuropathology, including the deposition of amyloid and spread of tau along connectional pathways. AGB101 (low dose levetiracetam) demonstrates efficacy on a range of molecular, synaptic, electrophysiological, functional and behavioral endpoints across models and species. In a Phase 2 study measuring hippocampal activity during a pattern separation memory test in patients with aMCI, AGB101 normalized hippocampal activity and improved performance on this specific memory assessment of hippocampal function. The HOPE4MCI trial is investigating the effects of AGB101 (220 mg) vs placebo in patients with MCI due to AD. The objective of the study is to assess the efficacy of AGB101 (low‐dose levetiracetam, 220 mg, extended release tablet) compared to placebo in subjects with mild cognitive impairment (MCI) due to Alzheimer’s disease (AD) using Clinical Dementia Rating‐Sum of Boxes (CDR‐SB) scores as the sole primary outcome. A substudy will evaluate levels of tau protein in the brain using tau PET ([18F]MK‐6240) at baseline and end of protocol. Method This is a multicenter, randomized, double‐blind, placebo‐controlled, 78‐week, fixed‐dose study evaluating AGB101 versus placebo as a treatment for slowing the progression of MCI due to AD. Inclusion criteria: Subjects must meet the following inclusion criteria at screening: 1) Subjects between 55 and 85 years old; 2) Have MCI due to AD consistent with the NIA‐AA criteria: MMSE (24‐30); CDR (0.5); Impaired delayed recall on the ISLT; essentially preserved ADLs' 3) Evidence of an amyloid‐positive PET scan Result The HOPE4MCI trial is currently underway. Sites are currently enrolling in the US and Canada with plans to expand to Europe. Up to date subject demographics, screen failure information, safety and dropout information will be presented at the meeting. Conclusion HOPE4MCI represents the first and only Phase 3 clinical trial targeting the reduction of hippocampal overactivity for slowing the progression of MCI due to AD.
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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 | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 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) | 0.008 | 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".