Table 2.5.
Volumetric MRI results in major recent clinical trials
| Agent | Drug-placebo difference at the end of study | Duration of study |
|---|---|---|
| AN1792 [116] | Greater atrophy in the active treatment group (significant for whole brain and ventricular volume; not the hippocampal volume) | 12 monthsa |
| Vitamin E or donepezil [117] | No drug-placebo difference in whole brain, ventricular, entorhinal cortex, or hippocampal volume with either treatment | 36 months |
| Tramiprosate [118] | Dose-dependent preservation of hippocampal volume (post hoc analysis) | 70 weeks |
| DHA [119] | No drug-placebo difference in whole brain volume, ventricular volume, or hippocampal volume | 18 months |
| Valproate [111] | Greater atrophy in the treatment group compared to the placebo group (whole brain, ventricular, hippocampal) | 24 months |
| Avagacestat [113] | No drug-pbo difference in whole brain, ventricular, or hippocampal volume | 24 weeks |
| Semagacestat [97] | No drug-pbo difference in entorhinal cortex or hippocampal volume | 76 weeksa |
| Bapineuzumab; ApoE carrier study [109] | No drug-pbo difference in whole brain volume | 71 weeks |
| Bapineuzumab; ApoE noncarrier study [109] | No drug-pbo difference in whole brain volume | 71 weeks |
| Solanezumab; Expedition [51] | No drug-pbo difference in whole brain or hippocampal volume | 80 weeks |
| Solanezumab Expedition II [51] | No drug-pbo difference in whole brain or hippocampal volume | 80 weeks |
| Azeliragon (TTP488) [120] | No drug-placebo difference in whole brain volume or hippocampal volume | 18 months |
| Resveratrol [121] | Whole brain volume decreased and ventricular volume increased significantly in the treatment group compared to the placebo group | 52 weeks |
| Avagacestat [114] | Greater atrophy rates were observed in the active treatment group for ventricular and whole brain volumes; differences were significant at weeks 24 and 56 but not at 104 (possibly due to small the number of patients remaining the study) | 104 weeks |
| Avagacestat [114] | No drug-placebo difference in whole brain, ventricular, or hippocampal volume at study end; greater atrophy I the treatment group at weeks 24 and 56 | 104 weeks |
| Gantenerumab [69] | No drug-pbo difference in either dose group for whole brain, ventricular, or left-right hippocampal volume | 100 weeks |
| IVIG [110] | No drug-placebo difference in whole brain volume, ventricular volume, or hippocampal volume | 18 months |
| Solanezumab; Expedition III [52] | No drug-pbo difference in whole brain or ventricular volume | 76 weeks |
| Crenezumab [52] | No drug-pbo difference in ventricular volume or whole brain volume | 73 weeks |
| Verubecestat [46] | No significant drug-placebo difference in hippocampal volumes; numerically greater in the active treatment groups | 78 weeks |
BACE β-site amyloid precursor protein cleaving enzyme 1, DHA docosahexaenoic acid, GSI gamma-secretase inhibitor, GSK glycogen synthase kinase
IVIG intravenous immunoglobulin, mAb monoclonal antibody, MOA mechanism of action, pbo placebo
a
AN1792 and semagacestat trials were stopped before planned completion