Clinical Trials Logo

Clinical Trial Summary

The study will consist of a prospective observation of subjects in a natural history design. Disease progression will be monitored through clinical scales and video-oculography. Participants will be stratified in three groups: ataxic carriers, pre-ataxic carriers and non-carriers (controls). The following clinical scales will be applied in all subjects at baseline and at months 12 and 24: SARA, SCAFI, CCFS, NESSCA, INAS and ICARS. Oculomotor function will be registered using video-oculography (EyeSeeCam, InterAcoustics) at the same time points. Progression rates, effect sizes and responsiveness to change will be established for all parameters and results will be compared between candidate biomarkers.


Clinical Trial Description

Spinocerebellar ataxia type 3, also called Machado-Joseph disease (SCA3/MJD), is an autosomal dominant neurodegenerative disorder caused by a CAG expansion (CAGexp) on ATXN3. Over 20 years after the identification of the causal mutation, no form of prevention or treatment for this incapacitating condition was discovered. Similarly to other polyglutamine (polyQ) diseases, SCA3/MJD has a slow progression. Changes detected by clinical scales are small and, therefore, long intervals are needed to document disease progression. Clinical trials using clinical scales as primary outcomes should be very long, what makes them hardly feasible. In this context, the discovery of disease biomarkers is of utmost importance. Biomarkers associated with disease progression and/or with therapeutic intervention might be more easily verified than the changes measured by clinical scales. Seminal studies have demonstrated that oculomotor alterations and vestibulo-ocular reflex (VOR) impairment may be present even during presymptomatic periods. Our primary hypothesis is eye movement parameters including VOR, saccades, smooth pursuit and fixation measured by video-oculography could be biomarkers of SCA3/MJD disease progression. Besides that, the investigators aim to test if the candidate biomarkers present changes before disease-onset and if their responsiveness will be better than those of clinical scales, with more noticeable variations during a shorter period of time. The study will consist of a prospective observation of subjects in a natural history design. The investigators will monitor disease progression of the CAGexp carriers through clinical scales and video-oculography. At least 75 adult subjects from Rio Grande do Sul will be invited to participate in the study, and at least 50 of the participants will be asymptomatic subjects, at 50% risk of carrying the mutation. The study design will allow the subjects who wanted and the evaluators to stay blinded to subjects' genotypes. Participants will be stratified in three groups: ataxic carriers, pre-ataxic carriers and non-carriers (controls). Genotypes will be recorded separately to guarantee double blindness. For every pre-ataxic carrier, time until the disease-onset will be estimated by an equation previously built, in which individual age and CAGexp are the determinants. The following clinical scales will be applied in all subjects at baseline and at months 12 and 24: SARA, SCAFI, CCFS, NESSCA, INAS and ICARS. Oculomotor function will be registered in video and analyzed using the EyeSeeCam device. Progression rates of all variables will be estimated by mixed models, including as covariates age, groups and their interactions. Progression rates, effect sizes and responsiveness to change will be established for all parameters and results will be compared between candidate biomarkers. ;


Study Design


Related Conditions & MeSH terms


NCT number NCT04229823
Study type Observational
Source Hospital de Clinicas de Porto Alegre
Contact
Status Active, not recruiting
Phase
Start date March 28, 2017
Completion date August 2021

See also
  Status Clinical Trial Phase
Completed NCT00992771 - Study to Determine the Safety and Tolerability of Varenicline (Chantix®) in Treating Spinocerebellar Ataxia Type 3 Phase 2
Completed NCT01096082 - Safety and Efficacy of Lithium Carbonate in Patients With Spinocerebellar Ataxia Type 3 Phase 2/Phase 3
Active, not recruiting NCT03701399 - Troriluzole in Adult Subjects With Spinocerebellar Ataxia Phase 3
Active, not recruiting NCT04419974 - Astrocytic Markers and the Pre-ataxic Period of SCA3/MJD - BIGPRO Study Astrocytes
Terminated NCT05490563 - STRIDES - a Clinical Research Study of an Investigational New Drug to Treat Spinocerebellar Ataxia Phase 2/Phase 3
Withdrawn NCT04301284 - Study of CAD-1883 for Spinocerebellar Ataxia Phase 2
Withdrawn NCT01096095 - Pilot Study of Safety and Efficacy of Sodium Phenylbutyrate in Spinocerebellar Ataxia Type 3 Phase 2
Active, not recruiting NCT04268147 - Instrumented Data Exchange for Ataxia Study
Recruiting NCT01793168 - Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
Active, not recruiting NCT05826171 - Priming Motor Learning Through Exercise in People With Spinocerebellar Ataxia N/A
Recruiting NCT04399265 - Efficacy Of Oral Trehalose In Spinocerebellar Ataxia 3 N/A
Completed NCT03885167 - Identification of Biomarkers in Spinocerebellar Ataxia 3
Terminated NCT05160558 - A Pharmacokinetics and Safety Study of BIIB132 in Adults With Spinocerebellar Ataxia 3 Phase 1
Recruiting NCT05822908 - A Safety and Pharmacokinetics Trial of VO659 in SCA1, SCA3 and HD Phase 1/Phase 2
Not yet recruiting NCT03378414 - Umbilical Cord Mesenchymal Stem Cells Therapy (19#iSCLife®-SA) for Patients With Spinocerebellar Ataxia Phase 2
Completed NCT05502432 - Repetitive Transcranial Magnetic Stimulation in SCA3 Patients N/A
Recruiting NCT04714307 - Neuropsychiatry and Cognition in SCA3/MJD
Recruiting NCT05557786 - Treatment of Transcranial Alternating Current Stimulation(tACS)on Cerebellar Ataxia
Recruiting NCT01060371 - Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias