METHODS: This is a phase II, single-centre, double-blind, randomized placebo-controlled trial involving 75 individuals with mild to moderate PDD. Participants will be randomized into Ambroxol high-dose (1050 mg/day), low-dose (525 mg/day), or placebo treatment arms. Assessments will be undertaken at baseline, 6-months, and 12-months follow up times. Primary outcome measures will be the Alzheimer\'s disease Assessment Scale-cognitive subscale (ADAS-Cog) and the ADCS Clinician\'s Global Impression of Change (CGIC). Secondary measures will include the Parkinson\'s disease Cognitive Rating Scale, Clinical Dementia Rating, Trail Making Test, Stroop Test, Unified Parkinson\'s disease Rating Scale, Purdue Pegboard, Timed Up and Go, and gait kinematics. Markers of neurodegeneration will include MRI and CSF measures. Pharmacokinetics and pharmacodynamics of Ambroxol will be examined through plasma levels during dose titration phase and evaluation of GCase activity in lymphocytes.
CONCLUSIONS: If found effective and safe, Ambroxol will be one of the first disease-modifying treatments for PDD.
BACKGROUND: ClinicalTrials.gov NCT02914366, 26 Sep 2016/retrospectively registered.