Natural History of Oculomotor Neurophysiology in Ataxic and Pre-ataxic Carriers of SCA3/MJD

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Total Enrollment

95 participants

Study Classification

OBSERVATIONAL

Study Start Date

2017-03-28

Study Completion Date

2021-08-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Natural History Study of and Genetic Modifiers in Spinocerebellar Ataxias

NCT01060371

Spinocerebellar Ataxia Type 1 Spinocerebellar Ataxia Type 2 Spinocerebellar Ataxia Type 3 +1 more

UNKNOWN

Functional and Structural Imaging and Motor Control in Spinocerebellar Ataxia

NCT02488031

Spinocerebellar Ataxia

COMPLETED NA

Measuring Neurological Impairment and Functional Visual Assessment In Spinocerebellar Ataxias

NCT00654251

Spinocerebellar Ataxia

COMPLETED

Eye Movements and Visuo-spatial Perception

NCT03112408

Cerebellum Disease

COMPLETED NA

Autosomal Dominant Spinocerebellar Ataxias and Social Cognition

NCT07099651

Autosomal Dominant Spinocerebellar Ataxia (SCA1, 2,3,6,7,27B)

RECRUITING NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Spinocerebellar Ataxia Type 3 Machado-Joseph Disease

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Ataxic carriers

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