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Molecular Profile of the Evolution of Inclusion Body Myositis (IBM-RNAseq)

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ClinicalTrials.gov Identifier: NCT03299335
Recruitment Status : Recruiting
First Posted : October 3, 2017
Last Update Posted : January 16, 2018
Sponsor:
Information provided by (Responsible Party):
Centre Hospitalier Universitaire de Nice

Brief Summary:
This study aims at assessing the gene expression in the muscles of patients suffering from sporadic Inclusion Body Myositis (sIBM) at various stages of the disease, by comparison with muscles of control subject. The investigators use the RNA-seq technique to analyze the gene expression levels and potential alternate transcripts, including long non-coding RNAs (lncRNAs), in muscle tissue samples. The gene expression profiles will point to the genes of interest that can then become the object of future studies, in which epigenetic changes of these genes will be explored further. The value of those possible biomarkers will be assessed. The investigators will also evaluate the correlation between the gene expression profile, the degree of functional impairment, the histological picture and the presence or absence of autoantibodies.

Condition or disease Intervention/treatment Phase
Inclusion Body Myositis Other: Blood collection Not Applicable

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 15 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: Molecular Profile of the Evolution of Inclusion Body Myositis
Estimated Study Start Date : February 1, 2018
Estimated Primary Completion Date : February 1, 2019
Estimated Study Completion Date : February 1, 2019


Arm Intervention/treatment
Early-stage sIMB patients Other: Blood collection
assay of CPK and anti-cN-1A antibodies

Late-stage sIMB patients Other: Blood collection
assay of CPK and anti-cN-1A antibodies

Control subjects Other: Blood collection
assay of CPK and anti-cN-1A antibodies




Primary Outcome Measures :
  1. sIBM gene expression profile [ Time Frame: at 12 Months ]
    The expression of different genes in muscle tissue will be evaluated by RNA-seq and will allow to establish the IBM gene expression profile


Secondary Outcome Measures :
  1. CPK level [ Time Frame: at 12 Months ]
    The CPK level will be evaluated.

  2. Rate of cN-1A antibodies. [ Time Frame: at 12 Months ]
    Presence or absence of cN-1A antibodies will be evaluated.

  3. IWCI score [ Time Frame: at 12 Months ]
    The IWCI score will be evaluated.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria (early-stage sIBM patients):

  • Patient suffering from sIMB according to the ENMC 2011 criteria: "sIMB defined on histological and clinical features" with, on the inclusion visit day:

    • duration of the disease > 12 months;
    • onset of the disease > 45 years;
    • quadriceps weakness ≥ hip flexors and/or fingers flexors weakness > shoulder abductors;
    • CPK ≤ 15 x ULN.
  • Patient with available biopsy showing alterations compatible with an inflammatory myopathy (endomysial inflammatory infiltrate, overexpression of HLA class I), but not specific to sIMB, in particular with no associated degenerative and/or mitochondrial pathologies (protein aggregates: amyloid, p62, SMI-31, TDP-43; 15-18nm filaments; ragged red fibers; COX negative fibers).
  • Patient whose sIMB diagnosis has been histologically confirmed with a second muscle biopsy showing the typical histological hallmarks (endomysial inflammatory infiltrate, overexpression of HLA class I and an associated degenerative and/or mitochondrial pathology).
  • Patient who gave his consent for the use of the biological material from the muscle biopsy at the time of the diagnosis.
  • Patient affiliated to a social security regimen.
  • Signed and written informed consent.

Exclusion Criteria (early-stage sIBM patients):

  • Patient with a known medical record that could significantly influence the results of the study: auto-immune disease with conjunctive tissue inflammation (overlap myositis, rheumatoid arthritis, lupus, vasculitis, spondylarthritis, scleroderma, psoriatic arthritis), disease causing nerve-damage (Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis), auto-immune neuropathy (chronic polyradiculoneuritis and variants (multifocal motor neuropathy with conduction blocks, anti-MAG neuropathy)).
  • Presence of the following histological characteristics in the muscle biopsy pointing to degenerative and/or mitochondrial pathologies: protein aggregates (amyloid, p62, SM-31, TDP-43), 15-18nm filaments, ragged red fibers or fibers with decreased COX activity.
  • Patient who received one of the following treatments, prior to the first muscle biopsy:

    • anti-inflammatory drugs in the past week;
    • corticotherapy in the past month;
    • immunosuppressive agents in the past 3 months;
    • other treatments: chloridin, amiodarone, colchicine, vincristine in the past 6 months.
  • Patient under curators or guardianship.
  • Pregnant woman.

Inclusion Criteria (late-stage sIMB patients):

  • Patient suffering from sIMB according to the ENMC 2011 criteria: "sIMB defined on histological and clinical features" with, on the inclusion visit day:

    • duration of the disease > 12 months;
    • onset of the disease > 45 years;
    • quadriceps weakness ≥ hip flexors and/or fingers flexors weakness > shoulder abductors;
    • CPK ≤ 15 x ULN.
  • Patient whose sIMB diagnosis has been histologically confirmed with a muscle biopsy featuring the following characteristics: endomysial inflammatory infiltrate, rimmed vacuoles and protein aggregates (amyloid, p62, SM-31, TDP-43) or presence of 15-18nm filaments.
  • Patient who gave his consent for the use of the biological material from the muscle biopsy at the time of the diagnosis.
  • Patient affiliated to a social security regimen.
  • Signed and written informed consent.

Non-inclusion criteria (late-stage sIMB patients):

  • Patient with a known medical record that could significantly influence the results of the study: auto-immune disease with conjunctive tissue inflammation (overlap myositis, rheumatoid arthritis, lupus, vasculitis, spondylarthritis, scleroderma, psoriatic arthritis), disease causing nerve-damage (Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis), auto-immune neuropathy (chronic polyradiculoneuritis and variants (multifocal motor neuropathy with conduction blocks, anti-MAG neuropathy)).
  • Patient who received one of the following treatments, prior to the muscle biopsy that confirmed the diagnosis:

    • anti-inflammatory drugs in the past week;
    • corticotherapy in the past month;
    • immunosuppressive agents in the past 3 months;
    • other treatments: chloridin, amiodarone, colchicine, vincristine in the past 6 months.
  • Patient under curators or guardianship.
  • Pregnant woman.

Inclusion Criteria (control subjects):

  • Signed and written informed consent for the use of muscle tissue used collected for the diagnosis of a CPK elevation and/or myopathy and/or myalgias.
  • No signs of muscular weakness at the time of the muscle biopsy.
  • Age > 45, correlated to the age of sIMB patients, allowing for the constitution of a homogeneous group compared to sIMB patients.
  • Patient affiliated to a social security regimen.
  • Signed and written informed consent.

Non-inclusion criteria (control subjects):

  • Subject with a muscle biopsy showing signs of inflammation and/or vacuoles and/or dystrophy.
  • Subject with a known medical record that could significantly influence the results of the study: auto-immune disease with conjunctive tissue inflammation (overlap myositis, rheumatoid arthritis, lupus, vasculitis, spondylarthritis, scleroderma, psoriatic arthritis), disease causing nerve-damage (Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis), auto-immune neuropathy (chronic polyradiculoneuritis and variants (multifocal motor neuropathy with conduction blocks, anti-MAG neuropathy)).
  • Subject with a confirmed sIMB diagnosis.
  • Patient who received one of the following treatments, prior to the muscle biopsy that confirmed the diagnosis:

    • anti-inflammatory drugs in the past week;
    • corticotherapy in the past month;
    • immunosuppressive agents in the past 3 months;
    • other treatments: chloridin, amiodarone, colchicine, vincristine in the past 6 months.
  • Patient under curators or guardianship.
  • Pregnant woman.

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 ClinicalTrials.gov identifier (NCT number): NCT03299335


Contacts
Contact: Sabrina Sacconi, PU-PH +33 (0)4.92.03.57.57 sacconi.s@chu-nice.fr

Locations
France
Hôpital Pasteur 2 - Service Système Nerveux Périphérique, Muscle et SLA Recruiting
Nice, France, 06001
Contact: Sabrina Sacconi, PU-PH    +33 (0)4.92 .03.57.57    sacconi.s@chu-nice.fr   
Sponsors and Collaborators
Centre Hospitalier Universitaire de Nice

Responsible Party: Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier: NCT03299335     History of Changes
Other Study ID Numbers: 16-AOI-05
First Posted: October 3, 2017    Key Record Dates
Last Update Posted: January 16, 2018
Last Verified: January 2018

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Myositis
Myositis, Inclusion Body
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases