The Effect of Pramipexole on Metabolic Network Activity Compared With Levodopa in Early Parkinson's Disease
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.
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: 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|
- Longitudinal Change of Brain Network Activity [ Time Frame: twice, baseline and 1 year after baseline ] [ Designated as safety issue: Yes ]
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.
- Unified Parkinson's Disease Rating Score (UPDRS II, III) [ Time Frame: three times: baseline, 10 weeks, 1 year ] [ Designated as safety issue: Yes ]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.
- Parkinson's Disease Questionnaire (PDQ39) [ Time Frame: twice baseline and 1 year ] [ Designated as safety issue: Yes ]
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.
- Hoehn&Yahr (H&Y) Staging [ Time Frame: twice baseline and 1 year ] [ Designated as safety issue: Yes ]
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).
- Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). [ Time Frame: twice, at 10 weeks(V2) and 1 year(V5) ] [ Designated as safety issue: Yes ]
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)
|Study Start Date:||December 2011|
|Study Completion Date:||August 2014|
|Primary Completion Date:||August 2014 (Final data collection date for primary outcome measure)|
Active Comparator: pramipexole
0.375mg-4.5mg/day, flexible dosage according to an optimal improvement of movement dysfunction in PD patients
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.
Other Name: Sifrol
Active Comparator: Levodopa
Sinemet CR CR， Controlled Release
Drug: Sinemet CR
tablet of Sinemet CR, dosage of levodopa ranging from 200mg-600mg/day divided by 2 or 3 times, Duration is 1 year
Other Name: Sinemet CR 250' (Levodopa 200mg, and 50mg carbidopa)
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01470859
|Huashan Hospital Affiliated to Fudan University|
|Shanghai, Shanghai, China, 200040|
|Principal Investigator:||Jian Wang, MD||Fudan University|