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

Idiopathic Parkinson's Disease Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01470859
• Other study ID #: KY2011-283
• Status: Completed
• Phase: N/A
• First received: November 9, 2011
• Last updated: September 21, 2015
• Start date: December 2011
• Est. completion date: August 2014

Study information

• Verified date: September 2015
• Source: Huashan Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Ethics CommitteeChina: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: August 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 30 Years to 75 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Idiopathic Parkinson's Disease
• Parkinson Disease

Intervention

Drug:
• pramipexole
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.
• Sinemet CR
tablet of Sinemet CR, dosage of levodopa ranging from 200mg-600mg/day divided by 2 or 3 times, Duration is 1 year

Locations

Country	Name	City	State
China	Huashan Hospital Affiliated to Fudan University	Shanghai	Shanghai

Sponsors (2)

Lead Sponsor	Collaborator
Huashan Hospital	Boehringer Ingelheim

Country where clinical trial is conducted

China, 

References & Publications (6)

Huang C, Tang C, Feigin A, Lesser M, Ma Y, Pourfar M, Dhawan V, Eidelberg D. Changes in network activity with the progression of Parkinson's disease. Brain. 2007 Jul;130(Pt 7):1834-46. Epub 2007 Apr 30. — View Citation

Izumi Y, Sawada H, Yamamoto N, Kume T, Katsuki H, Shimohama S, Akaike A. Novel neuroprotective mechanisms of pramipexole, an anti-Parkinson drug, against endogenous dopamine-mediated excitotoxicity. Eur J Pharmacol. 2007 Feb 28;557(2-3):132-40. Epub 2006 Nov 14. — View Citation

Ma Y, Tang C, Spetsieris PG, Dhawan V, Eidelberg D. Abnormal metabolic network activity in Parkinson's disease: test-retest reproducibility. J Cereb Blood Flow Metab. 2007 Mar;27(3):597-605. Epub 2006 Jun 28. — View Citation

Parkinson Study Group. A randomized placebo-controlled trial of rasagiline in levodopa-treated patients with Parkinson disease and motor fluctuations: the PRESTO study. Arch Neurol. 2005 Feb;62(2):241-8. — View Citation

Tang CC, Poston KL, Dhawan V, Eidelberg D. Abnormalities in metabolic network activity precede the onset of motor symptoms in Parkinson's disease. J Neurosci. 2010 Jan 20;30(3):1049-56. doi: 10.1523/JNEUROSCI.4188-09.2010. — View Citation

Wang J, Ma Y, Huang Z, Sun B, Guan Y, Zuo C. Modulation of metabolic brain function by bilateral subthalamic nucleus stimulation in the treatment of Parkinson's disease. J Neurol. 2010 Jan;257(1):72-8. doi: 10.1007/s00415-009-5267-3. Epub 2009 Aug 7. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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	Yes
Secondary	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)	Yes