Ignite Creation Date:
2024-05-06 @ 2:44 PM
Last Modification Date:
2024-10-26 @ 1:37 PM
Study NCT ID:
NCT04419974
Status:
UNKNOWN
Last Update Posted:
2020-06-09
First Post:
2020-04-07
Brief Title:
Astrocytic Markers and the Pre-ataxic Period of SCA3MJD - BIGPRO Study Astrocytes
Sponsor:
Hospital de Clinicas de Porto Alegre
Organization:
Hospital de Clinicas de Porto Alegre
Study Overview
Official Title:
Biomarkers and Genetic Modifiers in a Study of Pre-ataxic and Ataxic SCA3MJD Carriers BIGPRO Study - Astrocytes
Status:
UNKNOWN
Status Verified Date:
2020-06
Last Known Status:
ACTIVE_NOT_RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The study will consist of a prospective observation of subjects in a natural history design The investigators will monitor changes of clinical scales quality of life messenger ribonucleic acid mRNA of candidate genes CCL11 TNFSF14 FCGR3B CLC and SLA and their peptide products when possible and eotaxin and S100B serum levels in order to determine which of them is are the most sensitive Participants will be stratified in three groups ataxic carriers pre-ataxic carriers and non-carriers controls
Detailed Description:
Spinocerebellar ataxia type 3 or Machado-Joseph disease SCA3MJD is an autosomal dominant neurodegenerative disorder caused by a CAG expansion at ATXN3 The gene product is a 42kDa protein called ataxin-3 widely expressed in neurons and peripheral tissues Physiological roles of ataxin-3 include at least ubiquitination and regulation of misfolded proteins cytoskeletal organization and focal adhesions development and transcriptional regulation most often as a transcriptional corepressor One purpose of the present study is to detect a possible association between altered transcription patterns of candidate genes and disease progression On the other hand previous evidences suggest that the disease process linked to polyQ aggregation in neuronal cell cell-autonomous process might be worsened by what happens outside the neuronal cell non-cell-autonomous process Initial evidences lead to the role of astrocytes This is a major depart from the traditional understanding of polyglutamine diseases and comprises the main focus of the present study
The main hypothesis of this study is that the SCA3MJD clinical features may be in part associated to astrocytic processes In order to test it peripheral level of LIGHT protein encoded by TNFSF14 and eotaxin encoded by CCL11 - both expressed in astrocytes - and of S100B a myelin damage marker will be measured The investigators speculate if they can be biomarkers of disease progression and of pathological process even before symptoms onset In case this is positive their responsiveness to change will be tested to check if it is better than those of clinical scales
The second aim is to test if disease progression can be associated with changes in the transcriptional pattern of candidate genes FCGR3B CLC and SLA
BIGPRO study - Astrocytes intends to identify variations in these candidates and validate them as SCA3MJD biomarkers The study will consist of a prospective observation of subjects in a natural history design Changes in clinical scales quality of life messenger ribonucleic acid mRNA of candidate genes CCL11 TNFSF14 FCGR3B CLC and SLA and their peptide products when possible and eotaxin and S100B serum levels will be monitored in order to determine which of them is are the most sensitive Participants will be stratified in three groups ataxic carriers pre-ataxic carriers and non-carriers controls For each asymptomatic carrier the time until start of disease will be estimated according to the individual CAG expanded sequence CAGexp and subjects age Clinical scales Scale for the Assessment and Rating of Ataxia SARA Neurological Examination Scale for SCA NESSCA International Co-operative Rating Scale ICARS Inventory of Non-ataxia Symptoms INAS SCA Functional Index SCAFI Composite Cerebellar Functional Severity Score CCFS and Quality of Life measurements EQ-5D and SF-36 will be applied at baseline at 12 months and at 24 months in all subjects all three groups Eotaxin TNFSF14 S100B and mRNAs will be measured in the same moments Progression rates of all these variables will be estimated through mixed-models including as covariates age group and their interactions
The main hypothesis of this study is that the SCA3MJD clinical features may be in part associated to astrocytic processes In order to test it peripheral level of LIGHT protein encoded by TNFSF14 and eotaxin encoded by CCL11 - both expressed in astrocytes - and of S100B a myelin damage marker will be measured The investigators speculate if they can be biomarkers of disease progression and of pathological process even before symptoms onset In case this is positive their responsiveness to change will be tested to check if it is better than those of clinical scales
The second aim is to test if disease progression can be associated with changes in the transcriptional pattern of candidate genes FCGR3B CLC and SLA
BIGPRO study - Astrocytes intends to identify variations in these candidates and validate them as SCA3MJD biomarkers The study will consist of a prospective observation of subjects in a natural history design Changes in clinical scales quality of life messenger ribonucleic acid mRNA of candidate genes CCL11 TNFSF14 FCGR3B CLC and SLA and their peptide products when possible and eotaxin and S100B serum levels will be monitored in order to determine which of them is are the most sensitive Participants will be stratified in three groups ataxic carriers pre-ataxic carriers and non-carriers controls For each asymptomatic carrier the time until start of disease will be estimated according to the individual CAG expanded sequence CAGexp and subjects age Clinical scales Scale for the Assessment and Rating of Ataxia SARA Neurological Examination Scale for SCA NESSCA International Co-operative Rating Scale ICARS Inventory of Non-ataxia Symptoms INAS SCA Functional Index SCAFI Composite Cerebellar Functional Severity Score CCFS and Quality of Life measurements EQ-5D and SF-36 will be applied at baseline at 12 months and at 24 months in all subjects all three groups Eotaxin TNFSF14 S100B and mRNAs will be measured in the same moments Progression rates of all these variables will be estimated through mixed-models including as covariates age group and their interactions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None