Neuropsychiatry and Cognition in SCA3/MJD

Neuropsychiatry and Cognition in the Context of Spinocerebellar Ataxia Type 3/Machado-Joseph Disease (SCA3/MJD)

This research investigates how cognitive-affective aspects evolve during the course of SCA3/MJD. Due to COVID-19 pandemics, this study protocol was adapted for online-only consultations. Evaluations happening after March 2020 have been done by videocall with patients, and no neurological evaluation was thus performed on these patients. A scale on Activities of Daily Living was added to the online protocol to replace SARA, SCAFI and CCFS scales.

Study Overview

• Status: Recruiting
• Conditions: Spinocerebellar Ataxia Type 3; Machado-Joseph Disease; SCA3; MJD
• Intervention / Treatment: Diagnostic test: Cognitive Testing; Diagnostic test: Psychiatric Evaluation; Diagnostic test: Clinical Neurological Evaluation; Diagnostic test: Emotional Attribution Evaluation; Diagnostic test: Activities of Daily Living; Diagnostic test: SCA3/MJD molecular diagnosis

Detailed Description

By the end of this study, the evaluated population will be composed of 144 participants: 36 ataxic SCA3/MJD carriers, 72 at 50% risk of carrying the SCA3/MJD mutation and 36 healthy controls. Ataxic subjects are invited to participate if they have an established molecular diagnosis of SCA3/MJD and have a SARA score greater than 2.5 points. At risk subjects are composed by the offspring of molecularly diagnosed SCA3/MJD subjects that have a SARA<3. Healthy controls belonging either to families living with the disease or to the general population are invited to participate according to how well they match with ataxic subjects included in the study. Subjects are invited to participate in the study and, after constentment procedures, cognitive-affective assessments and a scale on Activities of Daily Living (ADL) are performed on a videocall. At risk subjects collect a blood sample for double bilnd determination of their carrier status. Before March 2020, all procedures were performed in person and, instead of ADL, SARA, SCAFI and CCFS were obtained.

• Study Type: Observational
• Enrollment (Anticipated): 144

Contacts and Locations

• Study Contact: Name: Laura B. Jardim, MD, PhD; Phone Number: +55513359-8011; Email: ljardim@hcpa.edu.br
• Study Contact Backup: Name: Gabriela Bolzan, MD; Phone Number: +55513359-8011; Email: gbgabrielabolzan@gmail.com

Study Locations

• Brazil
  • Rio Grande Do Sul
    • Porto Alegre, Rio Grande Do Sul, Brazil, 90035-903
      • Recruiting
      • Hospital de Clinicas de Porto Alegre
      • Contact: Laura B. Jardim, MD, PhD; Phone Number: +555133598011; Email: ljardim@hcpa.edu.br
      • Contact: Gabriela Bolzan, MD; Phone Number: +555133598011; Email: gbgabrielabolzan@gmail.com
      • Principal Investigator: Laura B. Jardim, MD, PhD
      • Sub-Investigator: Gabriela Bolzan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Individuals with molecular diagnosis of SCA3/MJD will be recruited from the Medical Genetics Service database of Hospital de Clínicas 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. Healthy controls will be invited from the general population.

Description

Inclusion Criteria:

• Symptomatic:
• older than 18 year old;
• molecular diagnosis of SCA3/MJD;
• SARA>2.5.
• At 50% risk:
• older than 18 year old;
• have a parent with molecular diagnosis of SCA3/MJD;
• SARA<3.
• Healthy Controls
• older than 18 year old;
• no genetic relationship with a SCA3/MJD carrier.

Exclusion Criteria:

• Non agreement in signing the informed consent;
• Healthy Controls: having any history of genetic disorders in their families or any psychiatric or neurologic disorder.

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Symptomatic; Molecularly diagnosed SCA3/MJD Symptomatic subjects.	Diagnostic test: Cognitive Testing; Cross-sectional Cognitive evaluation with; CCAS Scale; Trail-Making Test parts A and B; Stroop Color-Word Test; Diagnostic test: Psychiatric Evaluation; Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.; Diagnostic test: Clinical Neurological Evaluation; Cross-sectional neurological evaluation with standardized clinical scales - SARA, SCAFI and CCFS.; Diagnostic test: Emotional Attribution Evaluation; Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).; Diagnostic test: Activities of Daily Living; Cross-sectional evaluation of Activities of Daily Living (ADLs) by means of Friedreich Ataxia Rating Scale Part II.
Non-related Controls; Controls matched with symptomatic by age and educational level.	Diagnostic test: Cognitive Testing; Cross-sectional Cognitive evaluation with; CCAS Scale; Trail-Making Test parts A and B; Stroop Color-Word Test; Diagnostic test: Psychiatric Evaluation; Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.; Diagnostic test: Emotional Attribution Evaluation; Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).
At 50% risk for SCA3/MJD group; The offspring of affected individuals with SARA<3. This group will be comprised of two subpopulations: pre-symptomatic individuals and related controls. The determination will be made upon molecular diagnosis to be done in a double-blind manner.	Diagnostic test: Cognitive Testing; Cross-sectional Cognitive evaluation with; CCAS Scale; Trail-Making Test parts A and B; Stroop Color-Word Test; Diagnostic test: Psychiatric Evaluation; Cross-sectional Psychiatric evaluation with Hamilton-Anxiety and Hamilton-Depression rating scales.; Diagnostic test: Clinical Neurological Evaluation; Cross-sectional neurological evaluation with standardized clinical scales - SARA, SCAFI and CCFS.; Diagnostic test: Emotional Attribution Evaluation; Cross-sectional emotional attribution evaluation by means of the Reading the Mind in the Eyes Test (RMET).; Diagnostic test: Activities of Daily Living; Cross-sectional evaluation of Activities of Daily Living (ADLs) by means of Friedreich Ataxia Rating Scale Part II.; Diagnostic test: SCA3/MJD molecular diagnosis; Double-blind molecular diagnosis for determination of the presence of the mutation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebellar Cognitive Affective Syndrome Scale	Study the performance on the Cerebellar Cognitive Affective Syndrome Scale of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls.	Through study completion, an average of 1 year
Trail-Making Test Part A and B	Study the performance on the Trail-Making Test Part A and B of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls.	Through study completion, an average of 1 year
Stroop Color-Word Test	Study the performance on the Stroop Color-Word Test of SCA3/MJD symptomatic subjects when compared to matched healthy controls and of pre-symptomatic subjects when compared to familial healthy controls.	Through study completion, an average of 1 year
Emotion Attribution impairment in SCA3/MJD	Study the performance of symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test.	Through study completion, an average of 1 year
Emotion Attribution in different phases of the disease	Study the performance of pre-symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test.	Through study completion, an average of 1 year
Hamilton Anxiety Rating Scale	Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Anxiety Rating Scale.	Through study completion, an average of 1 year
Hamilton Depression Rating Scale	Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Depression Rating Scale.	Through study completion, an average of 1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Scale for the Assessment and Rating of Ataxia (SARA)	Correlations between primary outcomes and SARA.	Through study completion, an average of 1 year
Composite Cerebellar Functional Severity Score (CCFS)	Correlations between primary outcomes and CCFS.	Through study completion, an average of 1 year
SCA Functional Index	Correlations between primary outcomes and SCAFI.	Through study completion, an average of 1 year
Friedreich Ataxia Rating Scale part II (FARS part II)	Correlations between primary outcomes and Activities of Daily Living from FARS part II.	Through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Hospital de Clinicas de Porto Alegre
• Investigators: Principal Investigator: Laura B. Jardim, MD, PhD, Hospital de Clinicas de Porto Alegre and Universidade Federal do Rio Grande do Sul

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2019
• Primary Completion (Anticipated): February 1, 2021
• Study Completion (Anticipated): August 1, 2023

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: January 15, 2021
• First Posted (Actual): January 19, 2021

Study Record Updates

• Last Update Posted (Actual): January 19, 2021
• Last Update Submitted That Met QC Criteria: January 15, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Genetic Diseases, Inborn; Neurodegenerative Diseases; Dyskinesias; Spinal Cord Diseases; Heredodegenerative Disorders, Nervous System; Cerebellar Diseases; Cerebellar Ataxia; Ataxia; Spinocerebellar Ataxias; Spinocerebellar Degenerations; Machado-Joseph Disease
• Other Study ID Numbers: 20190606

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: Data sharing will be done via direct contact with the Principal Investigator in order to preserve individual participants identities.
• IPD Sharing Time Frame: Data will become available after final statistical analysis and data publishing via direct contact with principal investigator.
• IPD Sharing Access Criteria: Investigators and researchers of the area
• IPD Sharing Supporting Information Type: Study Protocol; Informed Consent Form (ICF); Clinical Study Report (CSR)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No