Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts (OPMD)
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.
|Muscular Dystrophy, Oculopharyngeal||Procedure: Autologous myoblasts transplantation and myotomy||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts|
- 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. [ Time Frame: before the graft and at 2, 6, 12, 18 and 24 months after the graft ]
- 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 [ Time Frame: before the graft and at 2, 6, 12, 18 and 24 months after the graft ]
|Study Start Date:||April 2004|
|Study Completion Date:||October 2015|
|Primary Completion Date:||July 2015 (Final data collection date for primary outcome measure)|
All patients included
Procedure: Autologous myoblasts transplantation and myotomy
Graft of autologous cell muscles (myoblasts) isolated from unaffected limb muscles into the pharyngeal muscles of patients diagnosed as suffering from OPMD and surgical procedure (myotomy)
Other Name: autograft and surgery
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00773227
|Paris, France, 75020|
|Principal Investigator:||Jean Lacau-Saint Guily, MD, PH||Assistance Publique - Hôpitaux de Paris|