NCT04419974

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).

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
95

participants targeted

Target at P50-P75 for all trials

Timeline
Completed

Started Mar 2017

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 18, 2017

Completed
3.1 years until next milestone

First Submitted

Initial submission to the registry

April 7, 2020

Completed
2 months until next milestone

First Posted

Study publicly available on registry

June 9, 2020

Completed
6 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2020

Completed
8 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2021

Completed
Last Updated

June 9, 2020

Status Verified

June 1, 2020

Enrollment Period

3.7 years

First QC Date

April 7, 2020

Last Update Submit

June 3, 2020

Conditions

Keywords

SCA3/MJDSCA3MJDnatural historycytokinesastrocytesquality of life

Outcome Measures

Primary Outcomes (6)

  • Change in serum concentrations of Eotaxin

    pg/ml

    24 months

  • Change in serum concentrations of S100B

    ÎĽg/l

    24 months

  • Change in expression of TNFSF14

    Fold change (FC)

    24 months

  • Change in expression of CCL11

    Fold change (FC)

    24 months

  • Change in EQ-5D-3L (EuroQoL 5 Domains evaluated in 3 levels)

    Quality of life scale evaluating 5 domains and a visual analog scale. Domain scores increase with worsening in quality of life. In the visual analog scale, worse scores mean decrease in quality of life.

    24 months

  • Change in SF-36 (Short-form 36)

    Quality of life scale evaluating 8 domains through 36 questions. Domain scores decrease with worsening in quality of life.

    24 months

Secondary Outcomes (3)

  • Change in expression of FCGR3B

    24 months

  • Change in expression of CLC

    24 months

  • Change in expression of SLA

    24 months

Study Arms (3)

Ataxic carriers

Subjects with a CAG repeat expansion on ATXN3 and Scale for Assessment and Rating of Ataxia (SARA) of 3 points or more.

Diagnostic Test: Clinical Scales - BaselineDiagnostic Test: Blood Draw - BaselineDiagnostic Test: Quality of Life Assessment - BaselineDiagnostic Test: Clinical Scales - Follow-up 12 monthsDiagnostic Test: Blood Draw - Follow-up 12 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 12 monthsDiagnostic Test: Clinical Scales - Follow-up 24 monthsDiagnostic Test: Blood Draw - Follow-up 24 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 24 months

Pre-ataxic carriers

Subjects with a CAG repeat expansion on ATXN3 and Scale for Assessment and Rating of Ataxia (SARA) of less than 3 points.

Diagnostic Test: Molecular DiagnosisDiagnostic Test: Clinical Scales - BaselineDiagnostic Test: Blood Draw - BaselineDiagnostic Test: Quality of Life Assessment - BaselineDiagnostic Test: Clinical Scales - Follow-up 12 monthsDiagnostic Test: Blood Draw - Follow-up 12 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 12 monthsDiagnostic Test: Clinical Scales - Follow-up 24 monthsDiagnostic Test: Blood Draw - Follow-up 24 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 24 months

Related controls

Subjects without a CAG repeat expansion on ATXN3, but with a first degree relative affected by the disease.

Diagnostic Test: Molecular DiagnosisDiagnostic Test: Clinical Scales - BaselineDiagnostic Test: Blood Draw - BaselineDiagnostic Test: Quality of Life Assessment - BaselineDiagnostic Test: Clinical Scales - Follow-up 12 monthsDiagnostic Test: Blood Draw - Follow-up 12 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 12 monthsDiagnostic Test: Clinical Scales - Follow-up 24 monthsDiagnostic Test: Blood Draw - Follow-up 24 monthsDiagnostic Test: Quality of Life Assessment - Follow-up 24 months

Interventions

Molecular DiagnosisDIAGNOSTIC_TEST

Double-blind molecular diagnosis for the SCA3/MJD mutation.

Pre-ataxic carriersRelated controls

SARA, NESSCA, ICARS, INAS, SCAFI, CCFS will be applied on baseline.

Ataxic carriersPre-ataxic carriersRelated controls
Blood Draw - BaselineDIAGNOSTIC_TEST

Blood collection on baseline for evaluation of * Candidate genes expression * Serum proteins * Lymphocytic proteins

Ataxic carriersPre-ataxic carriersRelated controls

Participants fill out 2 self-reported quality of life questionnaires.

Ataxic carriersPre-ataxic carriersRelated controls

SARA, NESSCA, ICARS, INAS, SCAFI, CCFS will be applied 12 months after baseline for prospective evaluation.

Ataxic carriersPre-ataxic carriersRelated controls

Blood collection 12 months after baseline for prospective evaluation of * Candidate genes expression * Serum proteins * Lymphocytic proteins

Ataxic carriersPre-ataxic carriersRelated controls

Participants fill out 2 self-reported quality of life questionnaires for prospective evaluation.

Ataxic carriersPre-ataxic carriersRelated controls

SARA, NESSCA, ICARS, INAS, SCAFI, CCFS will be applied 24 months after baseline for prospective evaluation.

Ataxic carriersPre-ataxic carriersRelated controls

Blood collection 24 months after baseline for prospective evaluation of * Candidate genes expression * Serum proteins * Lymphocytic proteins

Ataxic carriersPre-ataxic carriersRelated controls

Participants fill out 2 self-reported quality of life questionnaires for prospective evaluation.

Ataxic carriersPre-ataxic carriersRelated controls

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)
Sampling MethodNon-Probability Sample
Study Population

Individuals with molecular diagnosis of SCA3/MJD will be recruited from the Medical Genetics Service database of Hospital de ClĂ­nicas de Porto Alegre, Brazil, by telephone calls or by invitation in the outpatient clinic. First degree relatives of these subjects at 50% risk of carrying the mutation will also be invited to participate.

You may qualify if:

  • Individuals with molecular diagnosis of SCA3/MJD
  • Individuals at 50% risk of inheriting SCA3/MJD mutation without any clinical manifestation

You may not qualify if:

  • Refusal to sign informed consent
  • Other diagnosed neurological conditions;
  • Diabetes Mellitus;
  • Chronic allergy (asthma, eczema, urticaria)
  • Eosinophilia on baseline

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital de Clinicas de Porto Alegre

Porto Alegre, Rio Grande do Sul, 90035-903, Brazil

Location

Related Links

MeSH Terms

Conditions

Machado-Joseph Disease

Condition Hierarchy (Ancestors)

Spinocerebellar AtaxiasCerebellar AtaxiaCerebellar DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesSpinocerebellar DegenerationsSpinal Cord DiseasesHeredodegenerative Disorders, Nervous SystemNeurodegenerative DiseasesAtaxiaDyskinesiasNeurologic ManifestationsGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

  • Laura B. Jardim, MD, PhD

    Hospital de Clinicas de Porto Alegre

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 7, 2020

First Posted

June 9, 2020

Study Start

March 18, 2017

Primary Completion

December 1, 2020

Study Completion

August 1, 2021

Last Updated

June 9, 2020

Record last verified: 2020-06

Data Sharing

IPD Sharing
Will share

Data sharing will be done via direct contact with the Principal Investigator in order to preserve individual participants identities

Shared Documents
STUDY PROTOCOL, ICF, CSR
Time Frame
Data will become available after final statistical analysis and data publishing via direct contact with principal investigator
Access Criteria
Investigators and researchers of the area

Locations