Table 1.
Sulfur-containing therapeutics in clinical trials
| Target (reference) | Drug | Trial status | Outcome | Clinical trial identifier |
|---|---|---|---|---|
| Cysteine based thiols | NAC | Phase II terminated | No benefit over placebo | NCT00903695 |
| Phase I | NA | NCT03493178 | ||
| Recruiting | ||||
| Cerefolin NAC | Observational | Unknown | NCT01370954 | |
| NAC/vitamin supplement | Phase II completed | Improved cognition and baseline performance | NCT01320527 | |
| Glutathione | GSH | Nutritional intervention | Recruiting | NCT03448055 |
| Completed; observational study | NCT01713816 | |||
| Alpha lipoic acid [84, 85] | Fish oil/APA | Phase I/Phase II | Completed; no significant benefit | NCT00090402 |
| NCT01058941 | ||||
| Lipoic acid/vitamin E/vitamin C | Phase I | No change in Tau pathology | NCT00117403 | |
| 5HT6 receptor antagonist [224] | Interpirdine (SB-742457) | Phase III | Terminated due to lack of efficacy | NCT02586909 |
| NCT02585934 | ||||
| SAM-315 | Phase II | Failed to show benefit over donepezil | NCT00710684 | |
| NCT00708552 | ||||
| NCT00348192 | ||||
| NCT00224497 | ||||
| Phase I | Completed | NCT00551772 | ||
| Phase I | Discontinued | NCT00480467 | ||
| NCT00479440 | ||||
| NCT00474552 | ||||
| Sulfonic acid | Homotaurine (Tampiprostate, ALZ-801, 3APS, Alzhemed) | Phase III | Discontinued, failed to improve cognition | NCT00088673 |
| NCT00217763 | ||||
| NCT00314912 | ||||
| Phase II completed | No significant benefit over placebo | NCT04422743 | ||
| Phase I | Completed; well tolerated in healthy subjects | NCT04157712 | ||
| NCT04585347 | ||||
| Sulfonamide, BACE-1 inhibitors [286, 305] | MK-8931 (Verubecestat) | Phase III terminated | Failed to show efficacy | NCT01953601 |
| MK-8931 (Verubecestat) [286] | ||||
| Phase II/ | Reduced Aβ levels in MCI patients, discontinued due to adverse events | NCT01739348 | ||
| Phase III | ||||
| Phase II discontinued | ||||
| Phase I | Completed; well tolerated in subjects | NCT02910739 | ||
| NCT01537757 | ||||
| NCT01496170 | ||||
| Lanabecestat (LY3314814) | Phase III | Terminated, no efficacy over placebo | NCT02783573 | |
| NCT02972658 | ||||
| Phase II/ | Terminated, no efficacy over placebo | NCT02245737 | ||
| Phase III | ||||
| Phase I | Completed; well tolerated, no interactions with other drugs | NCT02406261 | ||
| NCT02540668 | ||||
| LY2886721 | Phase I | Completed; well tolerated, lowered plasma Aβ levels in AD patients | NCT01534273 | |
| NCT01807026 | ||||
| NCT01227252 | ||||
| NCT01133405 | ||||
| PhaseI/Phase II | Phase II terminated due to hepatotoxicity | NCT01561430 | ||
| SUVN-502 | Phase IIa | Completed; no significant benefit terminated, no significant benefit | NCT02580305 | |
| SAM-760 [287] | Phase II | NCT01712074 | ||
| Phase I | Completed; well tolerated in healthy subjects and | NCT01213355 | ||
| AD patients | NCT02005991 | |||
| NCT01159496 | ||||
| NCT00948662 | ||||
| γ-Secretase inhibitor | Avagacestat [306] | Phase II | Terminated due to gastrointestinal effects | NCT00890890 |
| NCT00810147 | ||||
| Phase I | Completed; well tolerated in healthy subjects | NCT01454115 | ||
| NCT01039194 | ||||
| NCT01042314 | ||||
| NCT00901498 | ||||
| NCT01057030 | ||||
| NCT00828646 | ||||
| Begacestat | Phase I | Completed; results unknown | NCT00959881 | |
| Thiazole, glutamate receptor inhibition | Riluzole | Phase II | Completed | NCT01703117 |
| Troriluzole (BHV-4157) | Phase II/Phase III | Active, ongoing | NCT03605667 | |
| Phenothiazine, tau aggregation inhibition | TRX 0237 (LMTM) | Phase III | Completed; failed to show efficacy | NCT01689233 |
| NCT01689246 | ||||
| NCT01626378 | ||||
| NCT02245568 | ||||
| Phase III | ||||
| Phase III | Ongoing | NCT03446001 | ||
| Phase II | Terminated for administrative reasons | NCT01626391 | ||
| TDZD | Rosiglitazone, Rosiglitazone XR | Phase III | terminated; no effects on cognition or memory | NCT00550420 |
| function | NCT00348140 | |||
| NCT00490568 | ||||
| NCT00428090 | ||||
| Phase II | Completed | NCT00381238 | ||
| NCT00334568 | ||||
| NCT00242593 | ||||
| Phase I | Completed; well tolerated in healthy and AD subjects | NCT00733785 | ||
| NCT00688207 | ||||
| NCT00468897 | ||||
| Thiourea | LY2811376 | Phase I | Completed; renal toxicity and | NCT00838084 |
| neurodegeneration found | ||||
| LY3202626 | Phase II | Terminated; low likelihood of statistical significance | NCT02791191 | |
| Phase I | Completed; well tolerated in AD patients and | NCT02555449 | ||
| reduced Aβ in CSF samples | NCT02323334 | |||
| NCT03023826 | ||||
| Atabecestat (JNJ-54861911) | Phase II/ | Terminated due to changes in liver enzyme levels | NCT02569398 | |
| PhaseIII | ||||
| Phase II | Completed; liver related adverse events | NCT02260674 | ||
| Phase I | Completed; well-tolerated in healthy and AD | NCT01827982 | ||
| patients | NCT01887535 | |||
| NCT01978548 | ||||
| Elenbecestat | Phase III | Active | NCT03036280 | |
| Thiourea, BACE-1 inhibitor | PF-06751979 | Phase I | Completed; well tolerated and reduced Aβ levels in blood | NCT03126721 |
| NCT02509117 | ||||
| NCT02793232 |