Idiopathic Parkinson's Disease
Conditions
Keywords
De Novo parkinson's disease, initial treatment, pramipexole, Levodopa, Parkinson's disease-related spatial covariance pattern
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.
Interventions
DRUGpramipexole
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.
DRUGSinemet CR
tablet of Sinemet CR, dosage of levodopa ranging from 200mg-600mg/day divided by 2 or 3 times, Duration is 1 year
Sponsors
Boehringer Ingelheim
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
30 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Longitudinal Change of Brain Network Activity | twice, baseline and 1 year after baseline | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Unified Parkinson's Disease Rating Score (UPDRS II, III) | three times: baseline, 10 weeks, 1 year | 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) | twice baseline and 1 year | 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 | twice baseline and 1 year | 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). | twice, at 10 weeks(V2) and 1 year(V5) | 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) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pramipexole 0.375mg-4.5mg/day, flexible dosage according to an optimal improvement of movement dysfunction in PD patients
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. | 15 |
| Levodopa Sinemet CR
Sinemet CR: tablet of Sinemet CR, dosage of levodopa ranging from 200mg-600mg/day divided by 2 or 3 times, Duration is 1 year | 14 |
| Total | 29 |
Baseline characteristics
| Characteristic | Pramipexole | Levodopa | Total |
|---|---|---|---|
| Age, Continuous | 63.87 years STANDARD_DEVIATION 5.68 | 61.9 years STANDARD_DEVIATION 6.66 | 62.9 years STANDARD_DEVIATION 6.14 |
| Region of Enrollment China | 15 participants | 14 participants | 29 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 14 | 2 / 15 |
| serious Total, serious adverse events | 0 / 14 | 0 / 15 |
Outcome results
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.
Time frame: twice, baseline and 1 year after baseline
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levodopa | Longitudinal Change of Brain Network Activity | Change from baseline (V5-V1) | 0.41 Z-score in PDRP | Standard Deviation 0.7 |
| Levodopa | Longitudinal Change of Brain Network Activity | Z score at baseline (V1) | 2.21 Z-score in PDRP | Standard Deviation 1.54 |
| Levodopa | Longitudinal Change of Brain Network Activity | Z score at 1 year (V5) | 2.29 Z-score in PDRP | Standard Deviation 1.24 |
| Pramipexole | Longitudinal Change of Brain Network Activity | Change from baseline (V5-V1) | 0.61 Z-score in PDRP | Standard Deviation 0.68 |
| Pramipexole | Longitudinal Change of Brain Network Activity | Z score at baseline (V1) | 3.61 Z-score in PDRP | Standard Deviation 1.77 |
| Pramipexole | Longitudinal Change of Brain Network Activity | Z score at 1 year (V5) | 4.09 Z-score in PDRP | Standard Deviation 1.07 |
p-value: 0.84t-test, 2 sided
p-value: 0.93t-test, 2 sided
p-value: 0.31t-test, 2 sided
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).
Time frame: twice baseline and 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levodopa | Hoehn&Yahr (H&Y) Staging | H&Y at 1 year（V5） | 1.65 units on a scale | Standard Deviation 0.47 |
| Levodopa | Hoehn&Yahr (H&Y) Staging | H&Y at baseline（V1） | 1.35 units on a scale | Standard Deviation 0.42 |
| Pramipexole | Hoehn&Yahr (H&Y) Staging | H&Y at baseline（V1） | 1.43 units on a scale | Standard Deviation 0.51 |
| Pramipexole | Hoehn&Yahr (H&Y) Staging | H&Y at 1 year（V5） | 1.82 units on a scale | Standard Deviation 0.54 |
p-value: 0.793indenpendent U test
p-value: 0.43independent U test
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.
Time frame: twice baseline and 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levodopa | Parkinson's Disease Questionnaire (PDQ39) | PDQ39 at baseline (V1) | 19.38 units on a scale | Standard Deviation 10.94 |
| Levodopa | Parkinson's Disease Questionnaire (PDQ39) | PDQ39 at 1 year (V5) | 20.36 units on a scale | Standard Deviation 16.49 |
| Pramipexole | Parkinson's Disease Questionnaire (PDQ39) | PDQ39 at baseline (V1) | 20.36 units on a scale | Standard Deviation 16.49 |
| Pramipexole | Parkinson's Disease Questionnaire (PDQ39) | PDQ39 at 1 year (V5) | 21.07 units on a scale | Standard Deviation 12.96 |
p-value: 0.72independent U test
p-value: 0.867independent U test
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)
Time frame: twice, at 10 weeks(V2) and 1 year(V5)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Levodopa | Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). | Patients with improvement at V2 | 6 participants |
| Levodopa | Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). | Patients with improvement at V5 | 2 participants |
| Pramipexole | Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). | Patients with improvement at V2 | 4 participants |
| Pramipexole | Patients With Clinical Improvement as Evaluated by Global Impression Scale (CGI). | Patients with improvement at V5 | 4 participants |
p-value: 0.345Chi-squared
p-value: 0.41Chi-squared
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.
Time frame: three times: baseline, 10 weeks, 1 year
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II (V2) | 5.8 units on a scale | Standard Deviation 3.5 |
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II at baseline (V1) | 7.3 units on a scale | Standard Deviation 3.5 |
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II at 1 year (V5) | 7.4 units on a scale | Standard Deviation 3.5 |
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III at baseline (V1) | 18.7 units on a scale | Standard Deviation 7.7 |
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III (V2) | 12.7 units on a scale | Standard Deviation 4.2 |
| Levodopa | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III at 1 year (V5) | 19.5 units on a scale | Standard Deviation 7 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III (V2) | 20.1 units on a scale | Standard Deviation 8.9 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III at baseline (V1) | 23.1 units on a scale | Standard Deviation 10.4 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II at baseline (V1) | 7.1 units on a scale | Standard Deviation 2.9 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II (V2) | 4.9 units on a scale | Standard Deviation 3.3 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS III at 1 year (V5) | 24.3 units on a scale | Standard Deviation 8.8 |
| Pramipexole | Unified Parkinson's Disease Rating Score (UPDRS II, III) | UPDRS II at 1 year (V5) | 8.4 units on a scale | Standard Deviation 3 |
p-value: 0.691independent U test
p-value: 0.706independent U test
p-value: 0.635independent U test
p-value: 0.341independent U test
p-value: 0.049independent U test
p-value: 0.874independent U test