The Effect of Pramipexole on Metabolic Network Activity Compared With Levodopa in Early Parkinson's Disease

Study Overview
=================
Brief Summary
-----------------
Levodopa and non-ergot dopaminergic agonists such as pramipexole are both recommended as the first-line symptomatic treatment for early untreated Parkinson's disease (PD), previous clinical trial indicated that initial pramipexole owns advantage over levodopa regarding motor complications, on the contrary, less adverse effect like freezing and severe somnolence favors initial treatment of levodopa. Thus, it remains controversial that initiation of which medication will be better for those patients with early PD. Parkinson's disease-related spatial covariance patter (PDRP) is a new biomarker which can represent the network activity of brain and severity of PD. Based on the literatures and our previous data, the investigators hypothesize that PDRP will be served as a biomarker to help us evaluate and compare the effect of levodopa or pramipexole on the progression of PD, which might be able to provide further evidence for clinicians to address the above critical issue.

Detailed Description
-----------------
CALM-PD study found that Pramipexole can reduce the occurrence of motor complication compared with Levodopa used as initiative treatment, but it still remains debatable that initiation of which medication will be better for those patients with De Novo PD. PDRP (Parkinson's disease-related spatial covariance pattern) is a biomarker which can represent the network activity of cortico-striato-pallido-thalamocortical pathways and highly reproducible with stable network activity in individual subjects. The study published in J Neuroscience in 2010 showed that the abnormal PDRP antecede the appearance of motor signs by about 2 years, indicating PDRP might be a very promising biomarker for identifying PD at its early stage. Moreover, PDRP is able to represent the progression and severity of PD as well. It was reported that Levodopa can reduce the PD-related network activity, and the degree of network suppression correlates with the clinical improvement. However, there is no study currently showing the impact of pramipexole on brain PDRP network compared with levodopa as initiative treatment.

Official Title
-----------------
a Pilot Follow-up Study of Investigating the Effect of Pramipexole on Metabolic Network Activity Compared With Levodopa in Chinese Patients With Early Parkinson's Disease

Conditions
-----------------
Idiopathic Parkinson's Disease

Intervention / Treatment
-----------------
* Drug: pramipexole
* Drug: Sinemet CR


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: idiopathic Parkinson's disease meeting United Kingdom (UK) brain bank criteria De Novo Hoehn&Yahr staging (H&Y) I-II Exclusion Criteria: Atypical Parkinsonism Pregnant or breast-feeding women those with abnormal Liver/kidney function those participating other clinical trials within 30 days before being enrolled for this trial.

Ages Eligible for Study
-----------------
Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: pramipexole<br>0.375mg-4.5mg/day, flexible dosage according to an optimal improvement of movement dysfunction in PD patients | Drug: pramipexole<br>* tablets, 0.375mg-4.5mg/day divided by 3 times according to the optimal improvement of motor dysfunction in PD patients. duration is 1 year.<br>* Other names: Sifrol;|
| Active Comparator: Levodopa<br>Sinemet CR CR， Controlled Release | Drug: Sinemet CR<br>* tablet of Sinemet CR, dosage of levodopa ranging from 200mg-600mg/day divided by 2 or 3 times, Duration is 1 year<br>* Other names: Sinemet CR 250' (Levodopa 200mg, and 50mg carbidopa);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Longitudinal Change of Brain Network Activity | The brain network activity is evaluated by Parkinson's disease-related spatial covariance pattern(PDRP) value (Z score). The change of brain network activity is calculated by the PDRP value (Z score) at V5 - the PDRP value (Z score) at V1. | twice, baseline and 1 year after baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Unified Parkinson's Disease Rating Score (UPDRS II, III) | baseline (1st visit, V1), completion of dosage titration within 10 weeks after baseline (2nd visit, V2), 1 year after baseline (final visit, V5) UPDRS II score 0-52 (13 items); UPDRS III score 0-56 (14 items); The more scores,the more severe; the two scales were evaluated separately. | three times: baseline, 10 weeks, 1 year | 
| Parkinson's Disease Questionnaire (PDQ39) | The PDQ39 score was assessed at baseline (1st visit, V1) and 1 year after baseline (final visit, V5). PDQ39 score ranges from 0-156 (0-4 each item); the more score, the more severe. | twice baseline and 1 year | 
| Hoehn&Yahr (H&Y) Staging | The Hoehn and Yahr scale is a commonly used scale for describing how the symptoms of Parkinson's disease progress and the disease stages. Bigger numbers indicate more symptoms and disease progression. H&Y stage range from 0-5; the greater, the more severe. The H&Y stages of patients were evaluated at baseline (1st visit, V1), and 1 year after baseline (final visit, V5). | twice baseline and 1 year | 
| Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). | Patients with a score <= 2 (very much or much improved in relation to baseline) are considered as clinically improved. The numbers of participants with clinical improvement are reported here. The completion of dosage titration within 10 weeks after baseline (visit 2) and 1 year after baseline (final visit) | twice, at 10 weeks(V2) and 1 year(V5) | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
De Novo parkinson's disease, initial treatment, pramipexole, Levodopa, Parkinson's disease-related spatial covariance pattern