Treatment of Dysphagia in Oculopharyngeal Muscular Dystrophy by Autologous Transplantation of Myoblasts
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 2
- 主要终点
- 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.
研究概览
简要总结
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.
详细描述
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 '. The proliferative capacity of the myoblasts isolated from the muscle biopsies will be carried out by Vincent MOULY and KAMEL MANCHAOUI in the UMR 7000 CNRS directed by Dr Butler-Browne and the cells will be amplified prior to grafting in the Cellular laboratory therapy of Dr MAROLLEAU; The clinical trial will be controlled by a specifically selected committee of five.
Description of the trial In the first step of this study patients will be selected for inclusion in the trial according to the following criteria : 1: men or women aged between 18 and 75 years ; 2: genetic confirmation and characterisation of OPMD 3: SSO dysfunction confirmed by the stasis of saliva or food above the sphincter visualised by fibroscopy and a defect in the opening of the SSO also confirmed by videofluoroscopy of swallowing; the SSO defect may be associated with a reduction in pharyngeal propulsion as revealed by fibroscopy and videofluoroscopy of swallowing 4: official signed consent of the patients to participate in this clinical trial.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
- •salivary or alimentary stasis at fibroscopy of swallowing above the UES,
- •decreased opening of the UES at videofluoroscopy of swallowing A decreased of the pharyngeal propulsion may be associated Written consent of the patient
排除标准
- •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.
结局指标
主要结局
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.
时间窗: before the graft and at 2, 6, 12, 18 and 24 months after the graft
次要结局
- 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)