Clinical trial NCT05874388: Characterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia
Official title: Characterisation of the Cognitive Profile of Patients Suffering From Friedreich's Ataxia
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Friedreich Ataxia
Keywords: FRATAXINE
Lead sponsor: Institut National de la Santé Et de la Recherche Médicale, France
Sponsor class: OTHER_GOV
First posted: 2023-05-24
Enrollment: 70
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: The study will involve two groups:

* a group of adolescents and adults symptomatic with FA with a confirmed molecular diagnosis, followed in the genetics department of the Necker Hospital
* a control group comprising subjects free of any motor or cognitive impairment, recruited from healthy relatives of patients (siblings, cousins, spouses) or for adults, among healthy people who are not related to the patients but who have been made aware of the existence of this research and who would meet the eligibility criteria and consent to participate in the study.

Brief summary: Friedreich's Ataxia (FA) Friedreich's Ataxia is a neurodegenerative disease caused by a homozygous expansion of the GAA triplet repeats of the frataxin gene (FXN). FA usually begins in childhood or adolescence. It affects both boys and girls. At the neurophysiological level, FA is characterised by neuronal loss affecting the dorsal root ganglia, spinal cord and cerebellum. At present, daily exercise is the only way to combat the disease. There is no cure for Friedreich's ataxia. Clinically, FA mainly combines balance, movement coordination, articulation (dysarthria) with cardiac involvement and sometimes diabetes . After a few years of evolution, walking is no longer possible. Recent data ; also indicate disturbances in information processing and cognitive functioning. In short, FA involves adolescents who progressively lose walking, writing and speech for some; however, each patient progresses differently with respect to the disease, and this is the case with respect to motor and cognitive symptoms.

Detailed description: The role of behavioural and cognitive assessment in the clinical trial The effectiveness of a treatment is ultimately determined by the elimination of the physiological cause of the disease and the alleviation of the symptoms that patients suffer. However, new treatments rarely eliminate all causes and symptoms of the disease. As long as the effectiveness of a treatment is unknown, it is subtle changes in parameters that decide whether the approach taken is worth pursuing. For a clinical trial which is supposed to evaluate the effectiveness of a treatment for Friedreich's Ataxia, it is therefore necessary to evaluate subtle changes in the functioning of the motor and cognitive system induced by the treatment. For this reason, the project is assembling a battery of tests that quantify the most important aspects of motor, cognitive and speech function in patients with FA. These tests are designed with the specific needs of FA patients in mind, i.e. on the one hand, the tests assess functions that are particularly important in view of the symptoms of Friedreich's disease indicated in the scientific literature, and on the other hand, the psychometric characteristics of the tests are adapted to the general abilities of FA patients. In this respect, it is important to point out that the expansion of the GAA repetition in people with Friedreich's disease varies from 150 to 1,000 triples (compared to 7 to 25 in the rest of the population), and that this large variation in the genotype of FA patients could potentially influence the cognitive profile of the participants. Previous studies have suggested the relationship between the number of repeats of the GAA triplet of the FXN gene and performance in cognitive assessment tests. Specifically, while in FA patients both alleles of the FXN gene contain an unusually high number of GAA repeats, performance in cognitive tests would correlate with the number of GAA repeats in the allele that contains fewer such repeats. Using this test battery, we are therefore able to achieve our main objective, i.e. to characterise the cognitive profile of FA patients as a function of the number of GAA triplet repeats of the FXN gene. Specifically, the test battery will establish whether motor, executive and speech symptoms affect patients differently according to their particular genetic characteristics.

Eligibility criteria: Inclusion Criteria:

* Patient group :

Patients aged 13 years or older Patients with FA confirmed by genetic study Compliant patients willing to undergo all tests Enrolled in a social security scheme or beneficiary of such a scheme

Control group :

Subjects aged 13 years or older Genetic characterisation to exclude the presence of alterations in the FXN gene No motor or cognitive impairment Compliant subjects willing to undergo all tests Membership in a social security scheme or beneficiary of such a scheme

Exclusion Criteria:

* Patient group :

Optic atrophy or decreased visual acuity Opposition of the patient, or of his parents if the patient is a minor, to participation in the study Non compliant patient according to the Investigator's opinion Person subject to a legal protection measure

Control group :

Alteration in the frataxin gene Optic atrophy or decreased visual acuity Opposition of the patient, or of his parents if the patient is a minor, to participation in the study Non-compliant patient in the opinion of the Investigator Person subject to a legal protection measure

Primary outcomes:
measure: characterization of the cognitive profile of patients suffering from Friedreich's Ataxia as a function of the number of GAA triplet repeats in the allele of the FXN gene that contains the least number of repeats.
timeFrame: through study completion, an average of 3 years
Secondary outcomes:
measure: Characterization of the motor profile of patients with Friedreich's Ataxia according to demographic variables and parameters related to the disease
timeFrame: through study completion, an average of 3 years
measure: Characterization of the executive profile of patients with Friedreich's Ataxia according to demographic variables and parameters related to the disease
timeFrame: through study completion, an average of 3 years
measure: Characterization of the speech production profile of patients with Friedreich's Ataxia according to demographic variables and parameters related to the disease
timeFrame: through study completion, an average of 3 years
measure: To determine which dimensions of cognitive functioning are affected in patients with Friedreich's Ataxia and to verify the sensitivity of tests aimed at evaluating these dimensions to detect deficits in patients compared to healthy healthy subjects.
timeFrame: through study completion, an average of 3 years
Other outcomes:
Locations:
city: Paris
country: France
facility: Hôpital Necker-Enfants Malades
Study officials:
affiliation: APHP
name: Benoit Funalot
role: PRINCIPAL_INVESTIGATOR
References: