Neuropsychiatry and Cognition in SCA3/MJD

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

• Registration Number: NCT04714307
• Lead Sponsor: Hospital de Clinicas de Porto Alegre

Brief Summary

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.

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 Timeline

• Study Start: 2019-12-13
• Study First Submitted: 2020-12-08
• Status Verified: 2021-01
• Study First Submitted QC: 2021-01-15
• Last Update Submitted: 2021-01-15
• Study First Posted: 2021-01-19
• Last Update Posted: 2021-01-19
• Primary Completion: 2021-02-01
• Study Completion: 2023-08-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 144

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-related Controls	Psychiatric Evaluation	Controls matched with symptomatic by age and educational level.
Symptomatic	Cognitive Testing	Molecularly diagnosed SCA3/MJD Symptomatic subjects.
Symptomatic	Emotional Attribution Evaluation	Molecularly diagnosed SCA3/MJD Symptomatic subjects.
Non-related Controls	Cognitive Testing	Controls matched with symptomatic by age and educational level.
Non-related Controls	Emotional Attribution Evaluation	Controls matched with symptomatic by age and educational level.
Symptomatic	Psychiatric Evaluation	Molecularly diagnosed SCA3/MJD Symptomatic subjects.
At 50% risk for SCA3/MJD group	Activities of Daily Living	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.
Symptomatic	Clinical Neurological Evaluation	Molecularly diagnosed SCA3/MJD Symptomatic subjects.
Symptomatic	Activities of Daily Living	Molecularly diagnosed SCA3/MJD Symptomatic subjects.
At 50% risk for SCA3/MJD group	SCA3/MJD molecular diagnosis	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.
At 50% risk for SCA3/MJD group	Cognitive Testing	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.
At 50% risk for SCA3/MJD group	Emotional Attribution Evaluation	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.
At 50% risk for SCA3/MJD group	Psychiatric Evaluation	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.
At 50% risk for SCA3/MJD group	Clinical Neurological Evaluation	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.

Primary Outcome Measures

Name	Time	Method
Cerebellar Cognitive Affective Syndrome Scale	Through study completion, an average of 1 year	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.
Stroop Color-Word Test	Through study completion, an average of 1 year	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.
Emotion Attribution in different phases of the disease	Through study completion, an average of 1 year	Study the performance of pre-symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test.
Hamilton Depression Rating Scale	Through study completion, an average of 1 year	Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Depression Rating Scale.
Trail-Making Test Part A and B	Through study completion, an average of 1 year	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.
Emotion Attribution impairment in SCA3/MJD	Through study completion, an average of 1 year	Study the performance of symptomatic SCA3/MJD carriers in the Reading the Mind in the Eyes Test.
Hamilton Anxiety Rating Scale	Through study completion, an average of 1 year	Study the profile of symptomatic and pre-symptomatic SCA3/MJD carriers in the Hamilton Anxiety Rating Scale.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Hospital de Clinicas de Porto Alegre; 🇧🇷 Porto Alegre, Rio Grande Do Sul, Brazil