Effects of Dopaminergic Therapy in Patients With Alzheimer's Disease
Condition: Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 2

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.
    

Intervention name(s): Rotigotine transdermal patch; Placebo
Intervention type(s): Drug; Other
Intervention description(s): Rotigotine transdermal patches 4mg/24hr; Placebo transdermal patches of the same size as for Rotigotine transdermal patches
Other intervention name(s): ROTIGOTINE; Placebo transdermal patch
Intervention MeSH terms: Rotigotine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Rotigotine; Dopamine