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Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy (CICS) (CICS)

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ClinicalTrials.gov Identifier: NCT02897921
Recruitment Status : Not yet recruiting
First Posted : September 13, 2016
Last Update Posted : September 14, 2016
Sponsor:
Information provided by (Responsible Party):

Study Description
Brief Summary:

Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation.

The aim of the study is to describe the clinical characteristics of single mutation carriers of recessive myopathy, through measuring serum creatine kinase, muscle strength, muscle degeneration (by MRI) and heart affection. The investigators will do this by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.

The aim is further to describe whether these characteristics are found primarily with specific mutations.


Condition or disease
Recessive Gene Myopathies

Detailed Description:

Background:

Many myopathies are inherited in a recessive manner, but in some of these recessively inherited disorders, clinical manifestations may potentially manifest in carriers of just a single mutation. This has recently been demonstrated by researchers for the recessively inherited limb girdle muscle dystrophy (LGMD) type 2A, where carriers of single mutations can also be symptomatic. In X-linked recessively inherited dystrophinopathies caused by mutations in the DMD gene on chromosome Xp21, female mutation carriers may also manifest with disease, although this is often milder than affected men. In the recently discovered LGMD2L, manifesting carriers are also suspected. Thus, according to statistics, too many persons evaluated for myopathy carry a single LGMD2L mutation.

Some previous studies have looked into the significance of being a single mutation carrier in recessive muscle disease. In dystrophinopathy, it was reported that 5 % of female DMD carriers reported myalgia and cramps, 17 % experienced mild-to-moderate muscle weakness and 8 % experienced dilated cardiomyopathy, with a mean onset age of approximately 30 years. Another study found that echocardiographic examination was abnormal in up to 38% of DMD female carriers - some with dilated cardiomyopathy, and some with left ventricle dilatation.

Overall, however significance of carrying a single mutation of recessive myopathy is widely unexplored. No study has yet investigated the characteristics of single mutation carriers of recessive myopathy in an observational, cross-sectional study.

Aim:

In this study, clinical characteristics of single mutation carriers of recessive myopathies will be investigated. The investigation will include sceletal muscle degeneration and strength, as well as cardiac status.

Recruitment and Methods:

Estimated total of subjects recruited is 200 with known recessive gene mutations, and 40 healthy controls. In former studies 40 healthy volunteers have already been investigated, thereby giving a total of 80 healthy controls. Recessive gene carrier recruits will be obtained via the Department of Clinical Genetics and Copenhagen Neuromuscular Center, Rigshospitalet, thus only including carriers aware of their carrier status.

2 days of testing per participant. Day one: Measuring S-creatine kinase level (blood sampling), muscle strength (Biodex 4 Isokinetic Dynamometer), ECG, and Holter monitor device application.

Day two: Holter monitor device removal, Dixon MRI analysis with gadolinium contrast medium, and echocardiography.

Healthy controls will take part in MRI-scanning and isokinetic dynamometer testing.

Trials are expected to be carried out between October 2016 and May 2020.


Study Design

Study Type : Observational
Estimated Enrollment : 240 participants
Observational Model: Case Control
Time Perspective: Cross-Sectional
Official Title: Clinical Importance of Carrier Status of Recessive Gene Mutations in Myopathy
Study Start Date : October 2016
Estimated Primary Completion Date : May 2020
Estimated Study Completion Date : August 2021

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Groups and Cohorts

Group/Cohort
Carriers of recessive gene mutations of myopathies

Patients with several different kinds of recessively inherited myopathy genes, such as for example Duchenne's Muscular Dystrophy, Becker's Muscular Dystrophy, Limb Girdle limb girdle muscle dystrophy (LGMD) type 2A and 2L etc.

Investigated by blood sampling, Biodex 4 Isokinetic Dynamometer, MRI analysis, ECG, Holter monitoring, and echocardiography.

Healthy controls
Healthy controls, investigated by blood sampling, Biodex 4 Isokinetic Dynamometer and MRI analysis.


Outcome Measures

Primary Outcome Measures :
  1. Cardiac status [ Time Frame: MRI of cardiac status and muscles takes around 1,5 hours ]
    We will use MRI with a contrast agent (gadolinium). Kidney function and contrast allergy status will be tested prior to use of contrast agent, and avoided if the participant is not suitable for contrast injection.

  2. Muscle tissue quality [ Time Frame: MRI of cardiac status and muscles takes around 1,5 hours ]
    Muscle tissue cross sectional area and fat percent will be investigated and measured by Dixon MRI scan.


Secondary Outcome Measures :
  1. Serum CK-levels [ Time Frame: Estimated time 5 minutes. ]
    Blood sampling

  2. Muscle strength [ Time Frame: Testing takes around 10-20 minutes ]
    Investigated by an isokinetic dynamometer (Biodex 4).

  3. ECG [ Time Frame: Estimated time: 5 minutes. ]
    ECG electrodes will be places on the subject's chest, and an electrocardigram will be measured.

  4. Holter monitor [ Time Frame: A Holter monitor device will be attached on test day 1, and worn until test day 2 (24-48 hours) ]
    The electrodes will be places on the chest and the monitor attached in a line around the neck. 24-48 hours of electrocardiogram will be measured.


Biospecimen Retention:   Samples With DNA
Blood samples

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
2 groups are studied: 1) Single mutation carriers of recessive myopathies. 2) Healthy controls.
Criteria

Single mutation carriers of recessive myopathy:

Inclusion Criteria:

  • Verified carrier status of recessive myopathy mutation before entry into the study
  • Age of 18 years or older

Exclusion Criteria:

  • Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
  • Claustrophobia
  • Pregnancy at the time of MRI
  • After investigators judgement

Healthy controls:

Inclusion Criteria:

• Age of 18 years or older

Exclusion Criteria:

  • Contraindications for MRI (pacemaker or other internal metal or magnetic devices)
  • Claustrophobia
  • Pregnancy at the time of MRI
  • After investigators judgement
Contacts and Locations

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): NCT02897921


Contacts
Contact: Tove Freja M Fornander, B. Sc. 35456135 ext 45 tove.freja.maria.fornander@regionh.dk
Contact: Nanna S Nielsen, B. Sc. 35456135 ext 45 Nanna.scharff.nielsen.01@regionh.dk

Locations
Denmark
Copenhagen Neuromuscular Center, Rigshospitalet, 3342
Copenhagen, Denmark, DK-2100
Sponsors and Collaborators
Rigshospitalet, Denmark
Investigators
Principal Investigator: Tove Freja M Fornander, B. Sc. Copenhagen Neuromuscular Center
More Information

Publications:
Responsible Party: Tove Freja Maria Fornander, Student researcher, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02897921     History of Changes
Other Study ID Numbers: H-16035677
First Posted: September 13, 2016    Key Record Dates
Last Update Posted: September 14, 2016
Last Verified: September 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: No plan

Additional relevant MeSH terms:
Muscular Diseases
Musculoskeletal Diseases
Neuromuscular Diseases
Nervous System Diseases