Unfortunately, in two companion Phase 3 trials involving nearly 1700 patients with mild Alzheimer’s and a separate Phase 3 trial in 220 patients with behavioral variant frontotemporal dementia (the largest trial ever in this cohort), treatment with 200 mg LMTM did not have any effect on pre-specified primary outcome measures compared to placebo controls. [80-82] However, methylene blue and related compounds are colorants that turn urine and feces blue, and all previous studies had included a low dose of active compound (8 mg daily) in placebo groups to improve blinding. Due to the possibility that this low dose may itself be effective, which would be a confound in previous analyses, an alternative active placebo was developed and a Phase 3 trial (LUCIDITY) is ongoing to test the low dose of LMTM in 450 patients with early AD (NCT03446001).
