Evaluation of the Efficacy of Rasagiline in Apathy in Drug-naïve Patients With Parkinson's Disease by a Multi-center Study

• Motor assessment : Unified Parkinson's Disease Rating Scale [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Depressive and anxiety symptoms : MADRS + Hamilton anxiety scale [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Self assessment of apathy : Starkstein [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Quality of life : PDQ 39 [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Cognitive assessment: MATTIS dementia rating scale, MMSE, executive functions battery [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Hyperdopaminergic symptoms : Parkinson's disease behavioral scale [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]
• Fatigue assessment : Parkinson Fatigue Scale [ Time Frame: at the visit 3 (after 3 months of treatment) ] [ Designated as safety issue: Yes ]

Among the psychiatric symptoms observed in the premotor phase of Parkinson's disease (PD) and/or in "de novo" patients, apathy is relatively frequent (estimated to 23%). However, the neuropathological bases of apathy are still unknown. However, recent data suggests that apathy could be linked to a more specific dopaminergic denervation in the ventral striatum.

Rasagiline increases the bioavailability of striatal endogenous dopamine by blocking the MAO-B. Some recent data suggest rasagiline could be effective to improve apathy in Parkinson's disease.

The primary outcome is to demonstrate a significant reduction of apathy using the Lille apathy rating scale (LARS) in drug naive patients with early diagnosed Parkinson's disease, using a treatment by rasagiline.

Study design :

Randomized, double-blind, rasagiline (1 mg) vs placebo study. Parallel group (randomization 1/1). Duration 3 months 16 recruiting centers in France

Population :

50 drug-naïve patients with Parkinson's disease, with apathy. 2 groups : 25 patients with placebo and 25 patients with rasagiline.

3 visits

• Visit 1 : inclusion / randomisation/ first study medication dispensation
• Visit 2 (1.5 month after V1) : first evaluation and second study medication dispensation.
• Visit 3 (3 months after V1, final visit) : second evaluation

• Drug-naïve Patients With Parkinson's Disease
• Apathy

• Drug: AZILECT®
• Drug: Placebo

• Experimental: rasagiline
  Randomized, double-blind, rasagiline (1 mg) vs placebo study. Parallel group (randomization 1/1). Duration 3 months 16 recruiting centers in France
  Intervention: Drug: AZILECT®
• Placebo Comparator: placebo
  Randomized, double-blind, rasagiline (1 mg) vs placebo study. Parallel group (randomization 1/1). Duration 3 months 16 recruiting centers in France
  Intervention: Drug: Placebo

Inclusion Criteria:

- Drug-naïve patients with Parkinson's disease (UKPDBB criteria)

• No dementia (Mattis dementia rating scale > 130; Mini Mental Sate Examination ≥26)
• No depression (MADRS < 15)
• Criteria of apathy from Robert et al (2009)
• At least mild apathy (≥-21 to Lille Apathy Rating Scale)
• Age : 35-70 y
• Affiliation to social security
• Agreement of patients

Exclusion Criteria:

• - Any antiparkinsonian treatment (L.dopa, dopamine agonists, MAO-B-I, amantadine, anticholinergics). Patients treated by dopamine agonists but who have stopped it more than 3 months before their inclusion can be included.
• Ongoing severe psychiatric or somatic diseases
• Others treatments :
• antipsychotics
• antidepressants and anxiolytics (exclusion if the treatment is not stable the month before inclusion)
• psychostimulants (methylphenidate, adrafinil, modafinil, deanol, vitamin C, sulbutiamine, glutamic acid, aspartic acid)
• any contra-indication according to SmPC
• patients under guardianship
• Women without efficient contraception
• Person who participate to an other study

• H. Lundbeck A/S, TEVA
• CHU Purpan
• Hôpital Haut-Levêque (Pessac)
• Centre Hospitalier de la Côte Basque (Bayonne)
• Centre Hospitalier Universitaire de Poitiers (Poitiers)
• CHU de Rennes
• Hôpital R Salendro (Lille)
• CHU Dupuytren
• University Hospital, Caen
• Hôpital Caremeau (NIMES)
• Centre Hospitalier Pays D'Aix (Aix en Provence)
• Hôpital de la Timone (MARSEILLE)
• University Hospital, Rouen
• Centre Hospitalier Universitaire, Amiens
• Centre Hospitalier Universitaire de Saint Etienne
• Fondation Rothschild (Paris)