Co-LEsions in Alzheimer Disease and Related Disorders (CLEM)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02052947|
Recruitment Status : Recruiting
First Posted : February 3, 2014
Last Update Posted : August 23, 2017
One of the crucial challenges for the future of Alzheimer's disease (AD) therapeutic approaches in elderly is to target the main pathological process responsible for disability and dependency. However, a progressive cognitive impairment occurring after the age of 70 is often related to mixed lesions of neurodegenerative and vascular origins. Whereas young patients are mostly affected by pure lesions, aging favors the occurrence of co-lesions of AD, vascular and Lewy body types. Pure DLB (Dementia with Lewy Body) and AD are distinct disorders but they often coexist in old age patients, the Abeta pathology of DLB/AD cases being different to that observed in patients with AD alone. Vascular dementia (VD) and AD with cerebrovascular disease (AD+CVD) are the leading causes of dementia next to AD alone. Lack of consensus persists about the diagnosis criteria for VD and AD+CVD, due in part to their clinical, pathological heterogeneity and the multiple pathological subtypes.
We do not know the precise role and weight of each brain lesion type in the disability progression in elderly. To target the actual pathological process, we need to disclose the functional weight of AD, Lewy body and vascular lesion types in elderly. Most of the studies report on functional and clinical abnormalities in patients with pure pathologies. Thus, co-morbid processes involved in the transition from an independent functional status to disability in the elderly with co-lesions still remain to be elucidated. Neuropathological examination often performed at late stages cannot answer this question at mild or moderate stages.
Brain MRI, Single Photon Emission Computed Tomography (SPECT) with DaTscan® and CSF biomarkers help routinely in performing the diagnosis of pure or mixed lesions responsible for dementia. The topography of the atrophy in MRI helps to provide information about the etiological diagnosis. Medial temporal lobe atrophy on MRI has good discriminatory power for AD compared to DLB and VD in pathologically confirmed cases. DaTscan® SPECT presents with good sensitivity and specificity at early stages of DLB. The good diagnosis value of CSF biological markers has led recently to their inclusion in the research diagnosis criteria of AD. Low Aβ1-42 and high levels of total tau and hyperphosphorylated tau isoforms appear to be the most sensitive and specific CSF biomarkers. Aβ1-42 is lowered in AD, as well as in other neurodegenerative diseases like DLB, VD. The combination of MRI, particularly medial temporal atrophy measures and vascular lesions on FLAIR MRI sequences, SPECT and CSF biomarkers seem to be of incremental value for the diagnosis AD, VD, DLB and mixed profiles.
The aim of this study is to identify the biomarkers (MRI, SPECT-DaTscan® and CSF), and their combination, that are the most predictive of functional disability in elderly presenting with a progressive cognitive decline related to AD, DLB, VD and all mixed patterns.
|Condition or disease||Intervention/treatment||Phase|
|Alzheimer's Disease Cerebrovascular Disease Lewy Body Disease||Radiation: SPECT-DaTscan||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||214 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Co-LEsions in Alzheimer Disease and Related Disorders|
|Study Start Date :||January 2014|
|Estimated Primary Completion Date :||July 2018|
|Estimated Study Completion Date :||October 2020|
U.S. FDA Resources
- Disability progression [ Time Frame: 2 years ]defined by the Disability Assessment in Dementia (DAD) scale (Gauthier, Gelinas et al. 1997; Gelinas, Gauthier et al. 1999)
- Neuropsychological inventory [ Time Frame: 2 years ]For the diagnosis and initial correlation with imaging and CSF markers, o For longitudinal assessments : MMSE (Folstein, Folstein et al. 1975), Batterie Rapide d'Efficience Frontale (BREF) (Dubois, Slachevsky et al. 2000) Adas-Cog (Rosen, Mohs et al. 1984)
- NeuroPsychiatric inventory [ Time Frame: 2 years ]Inventory described in Cummings, Mega et al. 1994
- Clinical/serum markers [ Time Frame: 2 years ]Disability progression and cognitive decline
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02052947
|Contact: Nawele Boublay||0472856302 ext +email@example.com|
|Villeurbanne, France, 69100|
|Contact: Nawele Boublay 00318.104.22.168.02 firstname.lastname@example.org|
|Principal Investigator: Pierre KROLAK-SALMON|