One-year Follow-up of Iron in Basal Ganglia - R2*: a Biomarker of Parkinson's Disease Progression?
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 160
- 试验地点
- 14
- 主要终点
- Change from baseline cerebral R2*
研究概览
简要总结
The study of non-invasive and reliable biomarkers to track progression of Parkinson's disease (PD) is essential while disease-modifying treatments are being developed. Many clinical biological or imaging biomarkers have been tested but no "gold standard" has been found as of yet. Among these, Magnetic Resonance Imaging (MRI) relaxometry using R2* measurement (R2* = 1/T2*), which is a validated marker for estimating brain iron concentration, appears to be an attractive technique because its safety, rapidly measured in clinical conditions and its ease to ensure individual longitudinal follow-up. Current data of cross sectional studies of R2*, which have shown an iron increase in Substantia Nigra (SN), led to suppose that it could be a biomarker of disease vulnerability. Recently, the investigators have conducted the first longitudinal follow-up of R2* (1.5 T MRI), which showed a rapid R2* increase in both parts of the SN and in the caudal putamen. We propose, here, a multicenter prospective study of one-year cohort follow-up of R2* variations (ΔR2*) in three regions of interest (ROIs) (the SN, the Ventral Tegmental Area (VTA) and the Putamen) of 160 patients with PD, using a 3 Tesla MRI, to evaluate the potential interest of R2* as a biomarker of disease progression. The variation of R2* (ΔR2*) will be correlated with clinical markers of disease progress, non-motor symptoms. 80 healthy controls subjects will also be included to assess the effect of aging on cerebral physiological iron levels.
详细描述
Use lay language.
The study of non-invasive and reliable biomarkers to track progression of Parkinson's disease is essential while disease-modifying treatments are being developed. Many clinical biological or imaging biomarkers have been tested but no "gold standard" has been found as of yet. Among these, Magnetic Resonance Imaging (MRI) relaxometry using R2* measurement (R2* = 1/T2*), which is a validated marker for estimating brain iron concentration, appears to be an attractive technique because its safety, rapidly measured in clinical conditions and its ease to ensure individual longitudinal follow-up. Current data of cross sectional studies of R2*, which have shown an iron increase in substantia nigra, led to suppose that it could be a biomarker of disease vulnerability. Recently, we have conducted the first longitudinal follow-up of R2* (1.5 T MRI), which showed a rapid R2* increase in both parts of the SN and in the caudal putamen. We propose, here, a multicenter prospective study of one-year cohort follow-up of R2* variations (ΔR2*) in three regions of interest (the substantia nigra, the ventral tegmental area and the putamen) of 160 patients with Parkinson's disease, using a 3 Tesla MRI, to evaluate the potential interest of R2* as a biomarker of disease progression. The variation of R2* (ΔR2*) will be correlated with clinical markers of disease progress, non-motor symptoms. 80 healthy controls subjects will also be included to assess the effect of aging on cerebral physiological iron levels.
Type of study : Interventional multicenter prospective study of cohort follow-up.
Number of centers : 6 (Clermont-Ferrand, Lyon, Grenoble, Paris, Limoges, Lille)
Study population :
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •for PATIENTS :
- •Parkinson's Disease (UK Parkinson's Disease Society Brain Bank Criteria).
- •No Deep Brain Stimulation (DBS).
- •From 40 to 80 years old.
- •Inclusion criteria for HEALTHY CONTROL SUBJECTS :
- •From 40 to 80 years old.
排除标准
- •for PATIENTS :
- •Dementia (MoCA < 24).
- •Atypical parkinsonism (MSA, PSP, ...).
- •Severe current psychiatric or somatic disease.
- •Iron treatments (Desferal® (deferoxamine), Ferriprox® (deferiprone) et Exjade® (deferasirox), Fumafer® (ferrous fumarate), Tardyferon® (ferrous sulfate (II)),...), Ferinject® (ferric carboxymaltose), Venofer® (iron sucrose),...).
- •Contra-indication to MRI (claustrophobia, pace maker,...).
- •Exclusion criteria for HEALTHY CONTROL SUBJECTS :
- •Neurological disease.
- •Psychiatric or somatic disease.
- •Dementia (MoCA < 24).
- •Iron treatments (Desferal® (deferoxamine), Ferriprox® (deferiprone) et Exjade® (deferasirox), Fumafer® (ferrous fumarate), Tardyferon® (ferrous sulfate (II)),...), Ferinject® (ferric carboxymaltose), Venofer® (iron sucrose),...).
- •Contra-indication to MRI (claustrophobia, pace maker,...).
研究组 & 干预措施
<5 years
160 PD patients divided into four subgroups of 40 patients according to disease duration:
- < 5 years
- Between 5 and 10 years
- Between 10 and 15 years
- > 15 years
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
Between 5 and 10 years
160 PD patients divided into four subgroups of 40 patients according to disease duration:
- < 5 years
- Between 5 and 10 years
- Between 10 and 15 years
- > 15 years
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
Between 10 and 15 years
160 PD patients divided into four subgroups of 40 patients according to disease duration:
- < 5 years
- Between 5 and 10 years
- Between 10 and 15 years
- > 15 years
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
> 15 years
160 PD patients divided into four subgroups of 40 patients according to disease duration:
- < 5 years
- Between 5 and 10 years
- Between 10 and 15 years
- > 15 years
干预措施: Magnetic Resonance Imaging (MRI) (Procedure)
结局指标
主要结局
Change from baseline cerebral R2*
时间窗: at 1 year
Change from baseline cerebral R2\* quantification at 1 year in three regions of interest (Substantia Nigra, Ventral Tegmental Area and Putamen).
次要结局
- Change from baseline depression score(at 1 year)
- Change from baseline hyper and hypo dopaminergic symptoms scores(at 1 year)
- Change from baseline sleepiness score(at 1 year)
- Change from baseline Parkinson's disease clinical symptoms(at 1 year)
- Change from baseline severity of Parkinson's disease(at 1 year)
- Change from baseline activities of daily living(at 1 year)
- Change from baseline freezing(at 1 year)
- change from baseline cognitive function(at 1 year)
- Change from baseline autonomic functions score(at 1 year)
- Change from baseline non-motor symptoms score(at 1 year)
- Change from baseline apathy score(at 1 year)
- Change from baseline anxiety score(at 1 year)