Working… Menu
Trial record 36 of 280 for:    Genetic Diseases, Inborn AND Genome

Improvement of DIAgnostic and Phenotype-genotype Correlation Studies in Patients With MYOpathy Suspected of TITinopathy (DIAMYOTIT)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03998540
Recruitment Status : Not yet recruiting
First Posted : June 26, 2019
Last Update Posted : July 9, 2019
Information provided by (Responsible Party):
University Hospital, Montpellier

Brief Summary:
Due to the widespread use of NGS, TTN is emerging as a major causative gene in neuromuscular disorders, with high clinical heterogeneity. The mechanisms underlying the phenotypic variability and mode of inheritance (recessive or dominant) of titinopathies are poorly understood. They involve the primordial structural functions of titin on the formation and stability of the sarcomere, as well as its interactions with other proteins. We identified by NGS, in patients with skeletal myopathy (with or without cardiomyopathy), several potentially disease causing TTN variants. The specific aims of the present project are to implement functional studies (transcripts, protein analyses, in vitro protein-protein interaction studies) to evaluate the effect of TTN variants on the transcripts and protein in order to perform phenotype-genotype correlation studies. We participate to the national "titin network" and to international efforts for the understanding of the molecular bases of titinopathies. Genomic characterisation opens the way to develop cellular models of titinopathy, derived from patient biopsies. This is also a mandatory first step for the design of novel therapeutic approaches.

Condition or disease Intervention/treatment
Myopathy Phenotypic Abnormality Genetic Disease Diagnostic Test: Western blot Other: Protein interaction studies

  Show Detailed Description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: Improvement of DIAgnostic and Phenotype-genotype Correlation Studies in Patients With MYOpathy Suspected of TITinopathy
Estimated Study Start Date : July 2019
Estimated Primary Completion Date : June 2021
Estimated Study Completion Date : May 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Muscle Disorders

Group/Cohort Intervention/treatment
Patients with myopathy suspected of titinopathy
Patients with myopathy in which one or more potentially pathogenic TTN variants have been previously identified (index cases and related cases affected). Muscle biopsy performed previously
Diagnostic Test: Western blot
Western-blot analysis of a giant protein, with specific antibodies directed against C-ter and N-Ter of the protein

Other: Protein interaction studies
Analyses of several interacting proteins by specific Western-blot and in-vitro tests.

Primary Outcome Measures :
  1. Measurement of the relative quantity of titin protein [ Time Frame: enrollment ]
    Evaluated by Western blot: normal or not, characterization of anomalies if any

  2. Measurement of the relative size of titin protein [ Time Frame: enrollment ]
    Evaluated by Western blot: normal or not, characterization of anomalies if any

Secondary Outcome Measures :
  1. Measurement of consequences on interacting proteins [ Time Frame: during 2 years ]
    Evaluation by Western blot: normal or not

  2. Measurement of the consequences of TTN variants on titin transcripts [ Time Frame: 2 years ]
    Evaluation by RT-PCR studies from muscle biopsies

  3. Phenotype-genotype correlation studies [ Time Frame: 2.5 years ]
    Correlation of clinicobiological data

  4. Analyses of molecular bases of the different mode of inheritance of the disease [ Time Frame: 2.5 years ]
    Integrated analyses of the complete biological data and correlation with the familial data

  5. Mesurement of the level of interactions by in-vitro studies [ Time Frame: during 2 years ]
    Evaluation by Western blot: normal or not

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information
Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
patients with suspected titinopathy

Inclusion Criteria:

  • Patient followed by a neurologist or a pediatric neurologist.
  • Child or adult with congenital or progressive, proximal or distal myopathy
  • Identification by NGS analysis of variant(s) in the potentially pathogenic TTN gene(s)
  • Muscle biopsy performed previously
  • Collection of the patient's (or one of his legal representatives if minor) non-opposition to participate in the present study and for the collection of the necessary biological material (muscle)
  • Patient affiliated to or benefiting from a social security scheme

Exclusion Criteria:

  • Absence of muscle sampling

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03998540

Layout table for location contacts
Contact: Mireille COSSEE, MCU PH 04 11 75 98 63
Contact: Sylvine PLAGNOL

Layout table for location information
CHU Montpellier
Montpellier, France, 34090
Sponsors and Collaborators
University Hospital, Montpellier

Layout table for additonal information
Responsible Party: University Hospital, Montpellier Identifier: NCT03998540     History of Changes
Other Study ID Numbers: RECHMPL18_0077
2018-A02287-48 ( Other Identifier: ANSM )
First Posted: June 26, 2019    Key Record Dates
Last Update Posted: July 9, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University Hospital, Montpellier:
western blot
Additional relevant MeSH terms:
Layout table for MeSH terms
Muscular Diseases
Genetic Diseases, Inborn
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases