Parkinson Disease Clinical Trial
Official title:
Dopaminergic Denervation and COMT Polymorphism in de Novo Patients With Parkinson's Disease
Parkinson's disease onset is clinically defined as the appearance of motor symptoms including akinesia, tremor and hypertonia. Several studies have shown that motor symptoms occur when at least 50 % of dopaminergic neurons are lost. However, there are evidence suggesting that the level of dopaminergic denervation is not homogenous at the time of diagnosis. Some patients have a higher level of dopaminergic loss at disease onset indicating the existence of compensation mechanisms. The aim of this study is to decipher how the metabolism of dopamine is involved in this compensation with a focus on the polymorphism of the COMT gene. This gene is expressed according to two variant: (i) COMT H that encodes a form of the enzyme with a high level of activity and (ii) COMT L that encode a form of the enzyme with a low level of activity. Thus, there are 3 possible genotypes in the population: (i) COMT HH associated with an increased degradation of dopamine, (ii) COMT LL associated with a decreased degradation of dopamine and (iii) COMT HH (intermediary between COMT HH and COMT LL). The hypothesis is that this polymorphism of the COMT gene may participate to compensation mechanisms in early PD. Patients with COMT HH genotype may have an earlier motor symptoms onset than patients with COMT LL genotype. To test this hypothesis, we will recruit 51 patients with de novo PD will be recruited (17 patients for each genotype). Given the distribution of COMT polymorphism in the population, a maximum sample of 76 patients will be screened to recruit 17 patients for each genotype. Clinical evaluation will include MDS-UPDRS, Non Motor Symptoms Scale, segmental symptoms scale, Montreal Cognitive assessment, MMSE, Frontal assessment battery and Parkinson's disease behavioral assessment scale (ECMP). All the patients will have a monophotonic emission tomography with I-123-Ioflupane in order to assess the level of dopaminergic denervation and an MRI scan with resting state study. Cerebrospinal fluid sampling will be optional and will allow direct measurements of dopamine metabolites. The main outcome measure will be the level of dopaminergic denervation on I-123-Ioflupane scans according to COMT genotype, age, gender and severity of motor symptoms on the MDS-UPDRS part 3. If this hypothesis is confirmed, this will allow to test the efficacy of COMT inhibitors in order to delay dopaminergic drugs initiation for PD patients.
Parkinson's disease onset is clinically defined as the appearance of motor symptoms including akinesia, tremor and hypertonia. Several studies have shown that motor symptoms occur when at least 50 % of dopaminergic neurons are lost. However, there are evidence suggesting that the level of dopaminergic denervation is not homogenous at the time of diagnosis. Some patients have a higher level of dopaminergic loss at disease onset indicating the existence of compensation mechanisms. The aim of this study is to decipher how the metabolism of dopamine is involved in this compensation with a focus on the polymorphism of the COMT gene. This gene is expressed according to two variants: (i) COMT H that encodes a form of the enzyme with a high level of aactivity and (ii) COMT L that encode a form of the enzyme with a low level of activity. Thus, there are 3 possible genotypes in the population: (i) COMT HH associated with an increased degradation of dopamine, (ii) COMT LL associated with a decreased degradation of dopamine and (iii) COMT HH (intermediary between COMT HH and COMT LL). The hypothesis is that this polymorphism of the COMT gene may participate to compensation mechanisms in early PD. Patients with COMT HH genotype may have an earlier motor symptoms onset than patients with COMT LL genotype. To test this hypothesis, 51 patients with de novo PD will be included (17 patients for each genotype). Given the distribution of COMT polymorphism in the population, a maximum sample of 76 patients will be screened for inclusion of 17 patients for each genotype. Only untreated patients will be included in the study in order to have a reliable assessment of motor severity without interference of dopaminergic drugs. The study will be scheduled as follow: - At the first visit (V1), inclusion criteria will be checked and patients will sign the informed consent. COMT genotype of selected patients will be analyzed. - Result of COMT genotype will be obtained within 4 weeks. Only the 17 first patients with each genotype will continue the study - For these patients, an evaluation visit with clinical assessment including MDS-UPDRS, Non Motor Symptoms Scale, segmental symptoms scale, Montreal Cognitive assessment, MMSE, Frontal assessment battery and Parkinson's disease behavioral assessment scale (ECMP) will be performed.. All the patients will have a monophotonic emission tomography with I-123-Ioflupane in order to assess the level of dopaminergic denervation. An MRI scan with resting state study will also be performed to assess the compensation mechanisms at the networks level. Cerebrospinal fluid sampling will be optional and will allow direct measurements of dopamine metabolites. The main outcome measure will be the level of dopaminergic denervation on I-123-Ioflupane scans according to COMT genotype with and without adjustment for age, gender and severity of motor symptoms on the MDS-UPDRS part 3. Secondary outcome measures will include: - level of dopaminergic denervation compared across the 3 genotypes (COMT HH, COMT HL and COMT HH) with and without adjustment for age, gender and motor scores - determination of functional compensation at the networks scale assessed on fMRI resting state scan according to dopaminergic denervation - determination of CSF dopamine metabolite profile at the time of diagnosis (CSF sampling will be optional). If this hypothesis is confirmed, this will allow to test the efficacy of COMT inhibitors in order to delay dopaminergic drugs initiation for PD patients. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT05415774 -
Combined Deep Brain Stimulation in Parkinson's Disease
|
N/A | |
Recruiting |
NCT04691661 -
Safety, Tolerability, Pharmacokinetics and Efficacy Study of Radotinib in Parkinson's Disease
|
Phase 2 | |
Active, not recruiting |
NCT05754086 -
A Multidimensional Study on Articulation Deficits in Parkinsons Disease
|
||
Completed |
NCT04045925 -
Feasibility Study of the Taïso Practice in Parkinson's Disease
|
N/A | |
Recruiting |
NCT04194762 -
PARK-FIT. Treadmill vs Cycling in Parkinson´s Disease. Definition of the Most Effective Model in Gait Reeducation
|
N/A | |
Completed |
NCT02705755 -
TD-9855 Phase 2 in Neurogenic Orthostatic Hypotension (nOH)
|
Phase 2 | |
Terminated |
NCT03052712 -
Validation and Standardization of a Battery Evaluation of the Socio-emotional Functions in Various Neurological Pathologies
|
N/A | |
Recruiting |
NCT05830253 -
Free-living Monitoring of Parkinson's Disease Using Smart Objects
|
||
Recruiting |
NCT03272230 -
Assessment of Apathy in a Real-life Situation, With a Video and Sensors-based System
|
N/A | |
Recruiting |
NCT06139965 -
Validity and Reliability of the Turkish Version of the Comprehensive Coordination Scale in Parkinson's Patients
|
||
Completed |
NCT04580849 -
Telerehabilitation Using a Dance Intervention in People With Parkinson's Disease
|
N/A | |
Completed |
NCT04477161 -
Effect of Ketone Esters in Parkinson's Disease
|
N/A | |
Completed |
NCT03980418 -
Evaluation of a Semiconductor Camera for the DaTSCAN™ Exam
|
N/A | |
Recruiting |
NCT04788693 -
Effects of Gait Rehabilitation With Motor Imagery in People With Parkinson's Disease
|
N/A | |
Completed |
NCT04942392 -
Digital Dance for People With Parkinson's Disease During the COVID-19 Pandemic
|
N/A | |
Terminated |
NCT03446833 -
LFP Beta aDBS Feasibility Study
|
N/A | |
Completed |
NCT03497884 -
Individualized Precise Localization of rTMS on Primary Motor Area
|
N/A | |
Completed |
NCT05538455 -
Investigating ProCare4Life Impact on Quality of Life of Elderly Subjects With Neurodegenerative Diseases
|
N/A | |
Recruiting |
NCT04997642 -
Parkinson's Disease and Movement Disorders Clinical Database
|
||
Completed |
NCT04117737 -
A Pilot Study of Virtual Reality and Antigravity Treadmill for Gait Improvement in Parkinson
|
N/A |