NCT03030586Unknown不适用
A Multi-centre Proof-of-performance Clinical Study to Validate Blood-based Biomarker Candidates for the Diagnosis of Alzheimer's Disease
Amoneta Diagnostics SAS13 个研究点 分布在 5 个国家目标入组 800 人开始时间: 2016年9月1日最近更新:
适应症
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 800
- 试验地点
- 13
- 主要终点
- Blood cell biomarkers for diagnosis of Alzheimer
研究概览
简要总结
The objective of the ADDIA clinical Proof-of-Performance study is to validate the performance of ADDIA' blood biomarkers for diagnosis of Alzheimer's disease (AD).
ADDIA clinical study is a multi-centre, non-interventional, prospective, proof-of-performance study with only one visit.
About 800 well-characterized subjects will be recruited into 3 groups in 2:1:1 ratio, namely patients with Alzheimer's disease (AD), patients with non-AD neurodegenerative disease (NAD) and 200 control subjects (healthy as compared to their age).
- 400 patients with Alzheimer's disease (AD): 200 patients with mild AD, 200 patients with moderate-to-severe AD,
- 200 patients with non-Alzheimer's neurodegenerative diseases (NAD),
- 200 controls (healthy as compared to their age).
详细描述
ADDIA study is dedicated to the proof-of-performance (PoP) of blood biomarkers for diagnosis of Alzheimer's disease (AD) and will recruit approximately 800 subjects (400 AD and 400 non-AD).
CONTEXT OF USE:
To quantify the performance of ADDIA' blood biomarkers for AD diagnosis (yes/no).
Since the main objective of this study is to establish the performance of ADDIA' blood cell-based biomarkers β-amyloid (Aβ) and protein kinase C (PKC) and corresponding assays and to seek approval as In-Vitro Diagnosis (IVD) test(s) specific for diagnosis of AD, and to validate the newly identified metabolomics and RNA signatures and selected protein biomarker candidates, samples will be used from:
- the patients recruited in the AD group and patients recruited in the non-AD neurodegenerative disorders (NAD) group who are accurately diagnosed during the pre-screening period, including by using three types of diagnostic methods: clinical neuropsychological scores, neuroimaging (at least volumetric structural MRI) and retrospective cerebrospinal (CSF) data: Aβ, total-Tau and p-tau biomarkers. Alternatively to absence of retrospective CSF data, retrospective Aβ PET /Tau PET scans can be used if compatible to diagnosis of respective diseases.
- the subjects recruited in the control group have no objective memory loss, normal results on neuropsychology tests, and normal neuroimaging findings for their age, as well as normal Aβ PET scan Tau PET scan and normal CSF Aβ, total-Tau and p-Tau concentration if retrospectively available.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 40 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •For all groups:
- •Female and male subjects aged 40 to 85 years.
- •Dated and signed informed consent by the subject (or its legal representative if applicable in accordance with the local regulations).
- •AD, NAD patients and control subjects will be age-matched and mean age similar in the three groups.
- •Able to comply with all study procedures.
- •For AD group:
- •Diagnosis of AD: typical and atypical AD.
- •MMSE score (measured in the last 3 months): < 21 for patients with moderate to severe AD. MMSE score > 21 in subjects with mild AD with sporadic or a familial form of AD due to mutation in APP or PSEN1 or PSEN2 genes.
- •FCSRT, MoCA tests (MoCA measured in the last 3 months).
- •Neuroimaging compatible with a diagnosis of AD:
- •At least quantitative volumetric structural MRI: volumes of hippocampus and cortical areas.
- •Visual semi-quantitative MRI if practiced shall show medial temporal lobe atrophy (MTA) and parietal atrophy with visual rating (semi-quantitative) on the MTA-score (e.g. Scheltens' scores 0-4). MTA score must be ≥ 2 in patients aged 40-75 years and ≥ 3 in patients aged above 75 years. For patients younger than 60 years, and with familial form of AD, who may have normal MTA-scores, Koedam score (0-3) for Parietal Atrophy showing atrophy of the precuneus characteristic of AD may be used with a Koedam score from 1 to
- •Other neuroimaging data (retrospectively available) including PET Amyloid scan and FDG PET are desired if practiced by clinical centres and if available.
- •Cerebrospinal fluid biomarker data (retrospectively available) showing positive levels of at least 2 out of 3 biomarkers: i.e. Aβ1-42 and tau (phosphorylated-Tau and/or total-Tau). Note: If retrospective CSF data are not available, retrospective Aβ PET and Tau PET data can be used.
- •For NAD group:
- •For all patients of the group NAD, except PSP subgroup (when PSP has a clear-cut typical phenotype, sometimes called Steele-Richardson phenotype), the CSF biomarker data must show levels for CSF biomarkers Aβ1-42, phosphorylated-Tau and total-Tau, compatible with the respective NAD subgroup. If retrospective CSF data are not available, retrospective Aβ PET and Tau PET data can be used.
- •Fronto-temporal dementia (FTD)
- •Diagnosis of probable behavioural FTD (bvFTD) for all subjects of this FTD subgroup, whether with familial or non-familial forms. If with familial form, the subject must be a member of family with a known mutation in one of the FTD related genes: MAPT, PGRN. The predominant phenotype in the kindred must be cognitive/behavioural (i.e. kindred in whom Parkinsonism or Amyotrophic Lateral Sclerosis is the predominant clinical phenotype among affected relatives is excluded).
- •Centrally rated frontal and/or anterior temporal atrophy score of 2 or greater on brain MRI.
- •MMSE score compatible. If currently taking an acetylcholinesterase inhibitor and/or memantine, the subject must have been taking such medication(s) for ≥3 months.
- •Dementia Lewy body (DLB)
- •DLB should be diagnosed when dementia occurs before or concurrently with Parkinsonism.
- •Patients diagnosed with probable DLB. Probable DLB can be made with the presence of two core features out of the following:
- •Fluctuating cognition with pronounced variations in attention and alertness,
- •Recurrent visual hallucinations that are typically well formed and detailed,
- •Spontaneous features of Parkinsonism.
- •Probable DLB is diagnosed with the presence of one or more of the above core features and one or more of the following suggestive features. Probable DLB should not be diagnosed on the basis of suggestive features alone:
- •REM sleep behaviour disorder,
- •Severe neuroleptic sensitivity,
- •Low dopamine transporter uptake in basal ganglia demonstrated by SPECT or PET imaging (if data retrospectively available).
- •Supportive diagnosis:
- •Generalized low uptake on SPECT/PET perfusion scan with reduced occipital activity (if data retrospectively available),
- •Abnormal (low uptake) MIBG myocardial scintigraphy,
- •Prominent slow wave activity on EEG with temporal lobe transient sharp waves.
- •MRI: Relative preservation of medial temporal lobe structures on CT/MRI scan.
- •Clinical Dementia Rating (CDR) score is greater than or equal to 0.
- •MMSE score compatible.
- •Patients with familial forms caused by mutation in genes SNCA, SNCB.
- •Parkinson's disease dementia (PDD)
- •Subjects with Parkinson's Disease Dementia (PDD) must have dementia after (not before) developing Parkinson's disease (PD).
- •PD is diagnosed by the 3 typical PD symptomatic findings:
- •rigidity, and
- •slowed movement (bradykinesia).
- •Subjects with dementia and with LRRK2 gene mutation (or with mutation in one of the following genes: PARK2 or SNCA, VPS35, PINK1, DJ1, ATP13A2, FBX07, SLC6A3, TAF1 are also included.
- •L-DOPA responsive (a good response to levodopa as practiced by clinical investigator, retrospectively to the study).
- •MMSE score < 21 for moderate to severe PDD and > 21 for mild PDD.
- •MRI: evidence of relevant structural abnormality (i.e. basal ganglia for Parkinsonism and potentially medio-temporal or cortical findings that may be related to dementia). Functional imaging techniques such as fluoro-dopa PET, FDG PET or SPECT to document the presence of dopaminergic dysfunction if retrospectively available.
- •Progressive Supranuclear Palsy (PSP)
- •Diagnosis of probable or possible PSP as defined by the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy (NINDS-SPSP) diagnostic criteria, and as summarized by Armstrong et al. (2013) for the conclusions on CBD criteria from an international consortium of behavioural neurology, neuropsychology, and movement disorders specialists):
- •Gradually progressive disorder,
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排除标准
- 未提供
结局指标
主要结局
Blood cell biomarkers for diagnosis of Alzheimer
时间窗: 18 Months
Proof of Performance of ADDIA' blood biomarker-based test
次要结局
- Biomarkers circulating in body fluids for diagnosis of Alzheimer and/or other dementia type(18 months)
研究者
研究点 (13)
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