Characterization of the Interruptions of the GAA Expansion and Study of Their Influence on the Severity of Friedreich's Ataxia

Friedreich Ataxia Clinical Trial

— INTREP-AF  

Official title:

Characterization of the Interruptions of the GAA Expansion and Study of Their Influence on the Severity of Friedreich's Ataxia : INTREP-AF

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04346238
• Other study ID #: RECHMPL20_0029
• Status: Active, not recruiting
• Start date: March 1, 2020
• Est. completion date: September 30, 2021

Study information

• Verified date: April 2020
• Source: University Hospital, Montpellier
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

Friedreich's ataxia (FA) is the most frequent recessive genetic ataxia with an estimated prevalence of 1/50 000. The first symptoms appear around the age of 10 years with a progressive course and the need for an armchair 10- 15 years after the first symptoms. More rarely the disease can present with a late onset (after the age of 25) with a picture characterized by spastic paraparesis and slower progression ("LOFA" for "Late Onset Friedreich Ataxia" or VLOFA for "Very Late Appearance of Friedreich's ataxia ").

AF is caused in 96% of cases by an expansion of GAAN triplets (N> 100 repeats) located in intron 1 of the FXN gene, present on the two alleles, and, in the rest of the cases, by an associated expansion a point mutation or a deletion in trans. During molecular diagnostics, it is not uncommon to find the presence of interruptions within the GAA expansion. This results in the absence and / or the shift of peak (s) within the chromatogram.

To date, only the partial correlation between the size of the expansion and the age of onset of Friedreich's ataxia has been established. In particular, very atypical forms of AF with a late onset (after the age of 25) are in particular explained by the low number of repetitions in the expansion, typically between 100 and 500 repetitions. However, the presence of an interruption could stabilize the size of the expansion and, therefore, be mainly associated with expansions of small sizes and therefore with a late onset of the disease.

The objective of this study is therefore to analyse and caracterize the presence and the type of interruptions of the GAA expansions in a group of patients with FA ; this data will be correlated with the age at onset of FA.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 120
• Est. completion date: September 30, 2021
• Est. primary completion date: March 30, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion criteria:

• Subjects with diagnosis of genetically confirmed Friedreich's Ataxia (AF) and :

• two expansions of GAAN triplets (> 100 repetitions or "premutation", corresponding to> 32 but <100 repetitions) located in intron 1 of the FXN gene present on the two alleles;

• symptomatic (SARA scale> 4);

• having signed a consent for the performance of genetic analyzes which also includes the authorization for the conduct of further studies for research purposes and the authorization for the collection, entry and computer processing of medical data, in all confidentiality. A newsletter on the principle of non-opposition will be sent.

Exclusion criteria:

• Patients with Friedreich's ataxia due to an expansion associated with a point mutation or a deletion in trans;

• Patients who, at the time of signing the genetic consent, objected to the use of their data for research purposes.

Related Conditions & MeSH terms

• Ataxia
• Cerebellar Ataxia
• Friedreich Ataxia

Intervention

Other:
• Reuse of existing data from patients' medical records
Reuse of existing data from patients' medical records

Locations

Country	Name	City	State
France	Uh Montpellier	Montpellier

Sponsors (4)

Lead Sponsor	Collaborator
University Hospital, Montpellier	Genetic Department , CHU Montpellier-France, Neurogenetic department, CHU Bordeaux, Neurology department, CHU La réunion

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Interruptions and date at onset	Study the correlation between the presence and type of interruptions (location within the expansion, nucleotide sequence: "GAAA", "GAG", etc.) and the age of onset of Friedreich's ataxia.	18 months
Secondary	Clinical correlation	Estimate the interaction between the presence and type of interruption and the age of onset of the various functional impacts (walking, cardiac involvement).	18 months