NCT03250741

Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease

Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease: a Phase II 24-week, Randomized, Double-blind Placebo Controlled Study.

• Status: Completed
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 94 (actual)
• Sponsor: I.R.C.C.S. Fondazione Santa Lucia · Academic / Other
• Sex: All
• Age: 50 Years – 85 Years
• Healthy volunteers: Not accepted

Summary

This is phase IIa 24-week, prospective, randomized, double-blind placebo controlled study. The study is designed to evaluate the efficacy, safety, and tolerability of transdermal patch of Rotigotine (RTG) versus placebo (PLC) as add-on therapy with AChEI in patients with mild AD according to the consensus diagnostic criteria and MMSE score of ≥18 and ≤24 at screening. Two groups of patients with mild AD will be involved (50 patients each). One group will be assigned to treatment with RTG 4 mg and the other one to PLC as add on to AChEI therapy (Rivastigmine). Clinical and neurophysiological measurements will be collected before and after drug administration.

Detailed description

The current study has the ambition to provide first time evidence that dopaminergic stimulation may have a clinical impact in patients with mild AD. Cognitive Assessment: Before and after the 24 weeks of treatment the ADAS-Cog, ADCS-ADL and the Frontal assessment battery (FAB) will be administered. FAB will be performed to measure changes in frontal executive functions (Apollonio et al, 2005) . Neurophysiological investigations will be performed to identify quantifiable biomarkers underlying the effects induced by dopamine agonist on the neurodegenerative brain. The application of recent neurophysiological tools, such as the combined use of transcranial magnetic stimulation (TMS) during electroencephalography (EEG) will allow to measure how dopamine agonists are able to modulate the cortical activity of the prefrontal cortex in AD patients (Kähkönen et al., 2005; Julkunen et al., 2008), likely trough DA terminals originating from the ventral tegmental nucleus, defining the neurophysiological biomarkers of clinical improvement For EEG-TMS recordings, a TMS-compatible EEG equipment will be used for recording EEG activity from the scalp (BrainAmp 32MRplus, BrainProducts). The EEG will be continuously acquired from 64 scalp sites positioned according to the 10-20 International System. To precisely position the coil over the cortical sites across different sessions, a neuronavigation system (Softaxic, E.M.S.) will be used. Neurophysiological changes induced by dopamine-agonist will be indexed by the following measures: corticospinal excitability, cortical reactivity, connectivity and plasticity. Specifically, the cortical reactivity and cortico-cortical connectivity will be evaluated respectively over the prefrontal cortex and between connected areas. We will employ TMS-evoked cortical responses (i.e., TEPs) as a novel probe of dopamine-agonist induced cortical excitability changes (Ilmoniemi et al., 1997; Komssi and Kahkonen, 2006; Julkunen et al., 2008; Miniussi and Thut, 2009; Miniussi et al., 2012; Premoli et al., 2014). To reach this aim, TEPs will serve as markers of left prefrontal cortex (PFC) reactivity whereas the spreading of their cortical activation will serve as an index of connectivity between targeted cortex and functionally connected areas underlying frontal cognitive network.

Conditions

• Alzheimer Disease

Interventions

Type	Name	Description
DRUG	Rotigotine transdermal patch	Rotigotine transdermal patches 4mg/24hr
OTHER	Placebo	Placebo transdermal patches of the same size as for Rotigotine transdermal patches

Timeline

• Start date: 2016-06-01
• Primary completion: 2018-11-01
• Completion: 2018-11-01
• First posted: 2017-08-16
• Last updated: 2018-12-17

Locations

1 site across 1 country: Italy