Muscular Dystrophy, Oculopharyngeal Clinical Trial
— OPMDOfficial title:
Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts
Verified date | November 2015 |
Source | Assistance Publique - Hôpitaux de Paris |
Contact | n/a |
Is FDA regulated | No |
Health authority | France: Ministry of Health |
Study type | Interventional |
The OCULO-Pharyngeal Muscular Dystrophy (OPMD) is a late onset hereditary muscle disease
which is characterised by the selective affection of the pharyngeal muscles resulting in
swallowing disorders, and by a ptosis from the dysfunction of the levator palpebral
superiors muscles. Swallowing disorders are determinant in the prognosis of the disease, and
potentially life-threatening deglutition, due to aspiration and denutrition. Degenerative
dystrophy of the pharyngeal muscles causes difficulties to prepulse the food bolus in the
pharynx, and the decreased relaxation of the cricopharyngeal muscle induced by the disease
leads to blockage of food in the upper esophageal sphincter. The most common treatment for
the dysphagia in OPMD is a myotomy of the upper esophageal sphincter muscles. However,
although this will relax the constriction of the upper esophageal sphincter muscles and
improve transitory the swallowing, it will not prevent the progressive degradation of the
pharyngeal muscles. This progressive loss of contractility will eventually result in
aspiration and severe difficulty in swallowing, increasing risk of aspiration pneumonia and
severe weight loss which are the most common causes of mortality in OPMD patients.
The protocol which we are proposing is a graft of autologous cell muscles (myoblasts)
isolated from unaffected limb muscles into the pharyngeal muscles of patients diagnosed as
suffering from OPMD. Our aim is to improve both swallowing and the contractile deficit
generated by the dystrophic pharyngeal muscles. A myotomy of the upper esophageal sphincter
will be carried out at the same time as the myoblast transplantation, since we have already
validated the improvement resulting from this surgery. Advantages of this new therapy in
OPMD is the autograft, without risks of rejection, and the graft of myoblasts into the
dystrophic pharyngeal muscles, above the myotomy of the upper esophageal sphincter muscles.
This model of cellular therapy has been studied through a preclinical study performed in
dogs, allowing to valid the procedure and its safety, as well as to study the survival
myoblasts grafted in the pharyngeal muscles.
This protocol is proposed for OPMD patients; it is firstly a safety study of both autograft
and surgical procedure. In addition, the autograft may improve the swallowing disorders and
life-threatening complications induced by aspiration and weight loss, resulting in a
potential individual benefit.
Status | Completed |
Enrollment | 30 |
Est. completion date | October 2015 |
Est. primary completion date | July 2015 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Man or woman <18-75> years old - Oculopharyngeal muscular dystrophy confirmed by genetic diagnosis (mutation of the GCG) on the chromosome 14) - Oculopharyngeal muscular dystrophy with UES dysfunction 1. salivary or alimentary stasis at fibroscopy of swallowing above the UES, 2. decreased opening of the UES at videofluoroscopy of swallowing A decreased of the pharyngeal propulsion may be associated Written consent of the patient Exclusion Criteria: - History of myotomy of the UES in the context of the Oculopharyngeal muscular - Dystrophy; - HIV, hepatitis B or C tuberculosis); - Lupus, rheumatoid polyarthritis, sarcoïdosis, collagenosis) ; - Other neuromuscular diseases ; - History of malignant tumor ; - History of neck radiotherapy ; - Renal failure (creatinine clearance <60ml/min) - Liver failure ; - Pregnancy ; - Follow up less than 24 months: - Patients who refuse to sign the consent; - No social security. |
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Country | Name | City | State |
---|---|---|---|
France | Hospital Tenon | Paris |
Lead Sponsor | Collaborator |
---|---|
Assistance Publique - Hôpitaux de Paris | Association Française contre les Myopathies (AFM), Paris |
France,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The principal evaluation of the efficiency of the graft will be based on the functional quality of the pharyngeal propulsion as determined by fibroscopy and videofluoroscopy of swallowing. | before the graft and at 2, 6, 12, 18 and 24 months after the graft | No | |
Secondary | on the global swallowing properties which will be evaluated by a quantitative test, by a questionnaire and by an evaluation of the tolerance. This evaluation will include a clinical examination at each visit consisting | before the graft and at 2, 6, 12, 18 and 24 months after the graft | No |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT02878694 -
Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
|
Phase 2/Phase 3 | |
Completed |
NCT00001871 -
Study of Muscle Abnormalities in Patients With Specific Genetic Mutations
|
N/A |