Table 2.
Study | Study design Number of patients | Disease | Treatment | Results |
---|---|---|---|---|
Aisen et al. (41) | RCT n = 58 |
Mild-to-moderate AD | Placebo, 3-APS 50, 100, or 150 mg bid during 3 months | 3-APS reduced CSF Aβ42 levels after 3 months of treatment |
Alphase Study.Aisen et al. (42) | RCT n = 1,052 |
Mild-to-moderate AD | Placebo, tramiprosate 100 mg or tramiprosate 150 mg bid during 78 weeks | No significant treatment effect.Trend toward a treatment effect for ADAS-cog and less HV loss. |
Abushakra et al. (29) | RCT n = 2,025 (pooled data from two phase III studies). |
Three subgroups of patients with mild-to-moderate AD:ApoE4 homozygotes, ApoE4 heterozygotes and non-carriers | Placebo, tramiprosate 100 mg or tramiprosate 150 mg bid during 78 weeks | In ApoE4/4 homozygotes on 150 mg bid significant effects on ADAS-cog and positive trends on CDR-SB.Intermediate efficacy in ApoE4 heterozygotes and no benefit in non-carriers. |
Abushakra et al. (43) | RCT n = 2,025 (pooled data from two phase III studies). |
Three subgroups of patients with mild-to-moderate AD:ApoE4 homozygotes, ApoE4 heterozygotes and non-carriers | Placebo or 100 mg bid, or 150 mg tramiprosate bid | Highest efficacy (ADAS-cog, CDR-SB, and DAD scores) in ApoE4/4 homozygotes on 150 mg bid with mild disease.The mild subgroup showed cognitive stabilization with no decline over 78 weeks, both ADAS-cog and DAD effects increased over time. |
Sabbagh et al. (46) | RCT A substudy of 257 subjects of Alphase Study. |
Mild-to-moderate AD patients ApoE4 homozygotes | Placebo or 100 mg bid, or 150 mg tramiprosate bid | Statistically significant efficacy in the mild subgroup (ADAS and CDR scores).Some benefit at week 78 as indicated by DAD scores. |
Spalletta et al. (33) | Controled study n = 33 |
aMCI | Tramiprosate 50 mg qd for 2 weeks and bid for the next year vs. untreated patients | Decreased volume loss in the left and right hippocampal tail, left and right fusiform gyrus, and right inferior temporal cortex.Improved short-term episodic memory performance. |
Bossù et al. (32) | Open trial n = 20 |
aMCI | Tramiprosate 50 mg qd for 2 weeks and bid for the next year | Compared to baseline, patients with ApoE4 allele showed a significant decrease in IL-18 and improved short-term episodic memory performance. |
Martorana et al. (50) | Observational retrospective study n = 245 |
aMCI and naMCI | Tramiprosate 100 mg qd | Significant improvements in cognitive decline (MMSE score) in patients with aMCI (at months 8 and 12), and naMCI (at month 4) |
Martorana et al. (51) | Open trial n = 10 |
aMCI | 100 mg tramiprosate during 4 weeks | Measurable changes of SLAI in aMCI patients. Potential role in enhancing cholinergic transmission by modulating the inhibitory cortical activity. |
Gauthier et al. (44) | RCT Subset of 312 Alphase Study subjects. |
Mild-to-moderate AD patients | Placebo, tramiprosate 100 mg or tramiprosate 150 mg bid during 78 weeks | Hippocampal atrophy slowing, beneficial effect on cognition (ADAS-cog) |
Saumier et al. (45) | RCT n = 1,052 (Alphase study data) |
Mild-to-moderate AD patients | Placebo, tramiprosate 100 mg or tramiprosate 150 mg bid during 18 months | ADAS-cog change scores and HV change correlate with vMRI. |
Ricciardi et al. (52) | RCT n = 47 |
Parkinson disease | Tramiprosate 100 mg bid vs. untreated patients | Benefits on non-motor symptoms (UPDRS-I) and beneficial effect on excessive sleepiness (Epworth Sleepiness Scale). |
Greenberg et al. (53) | RCT n = 24 |
Lobar intracerebral hemorrhage, with possible or probableCAA | Tramiprosate 50, 100, or 150 mg bid during 12 weeks | No significant changes on neurological function (NIHSS), daily functioning (Barthel Index), cognition (ADAS-cog), and executive function (EXIT25). |
3-APS, 3-amino-1-propanesulfonic acid; AD, Alzheimer's disease; ADAS, Alzheimer's Disease Assessment Scale; ADAS-cog, Alzheimer Disease Assessment Scale-cognitive subscale; aMCI, amnestic MCI; ApoE4, Apolipoprotein E4; ε4 allele of the apolipoprotein E gene; bid, twice daily; CAA, cerebral amyloid angiopathy; CDR-SB, Clinical Dementia Rating Scale, sum of boxes; DAD, Disability Assessment for Dementia; HV, hippocampus volume; MCI, Mild Cognitive Impairment; MMSE, Mini Mental State Examination; naMCI, non-amnestic MCI; NIHSS, NIH Stroke Scale; qd, daily; RCT, randomized controlled trial; SLAI, short latency afferent inhibition; UPDRS, Unified Parkinson's Disease Rating Scale; vMRI, volumetric magnetic resonance imaging.