Clinical Trial: Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts

Brief Summary:

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 t

Detailed Summary:

OCULO-Pharyngeal Muscular Dystrophy (OPMD) is characterised by the selective affection of the superior sphincter muscles of the oesophagus (SSO) and the pharyngeal.muscles resulting in dysphagia. The most common treatment for the dysphagia induced by this disease is a myotomy. However, although this will relax the constriction and improve swallowing it will not prevent the progressive degradation of the pharyngeal muscles. This progressive loss of contractility will eventually result in false routes and severe difficulty in swallowing, increased risk of pulmonary infection and severe weight loss which are the most common causes of mortality in these patients.

Concept:

The protocol which we are proposing is a pilot study in which autologous myoblasts isolated from unaffected limb muscles will be grafted into the pharyngeal constrictor muscles of patients diagnosed as suffering from OPMD. Our aim is to improve both swallowing and the contractile deficit generated by the dystrophic pharyngeal constrictor muscles. A myotomy of the SSO will be carried out at the same time as the myoblast transplantation, since we have already validated the improvement resulting from this surgery even though we know that this will provide only a partial and transitory improvement.

Type of trial: This is a multicentric trial with a direct benefit for the patient in which 10 patients will receive an autologous transplantation of myoblasts. Due to the possibility that a certain number of patients may withdraw from the study we have decided to include initially a maximum of 15 patients. The PHRC for this clinical trial was accepted in 2002 and the official promotor is the AP-HP. The patients will be selected by the different promotors but will be followed in the 'Service d'ORL of TENON Hospital '. Th
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: 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 ]

Original Primary Outcome: Same as current

Current Secondary Outcome: 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 ]

Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: October 15, 2008
Date Started: April 2004
Date Completion:
Last Updated: November 19, 2015
Last Verified: November 2015