NCT00773227

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 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
30

participants targeted

Target at P25-P50 for phase_2

Timeline
Completed

Started Apr 2004

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

April 1, 2004

Completed
4.5 years until next milestone

First Submitted

Initial submission to the registry

October 15, 2008

Completed
1 day until next milestone

First Posted

Study publicly available on registry

October 16, 2008

Completed
6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2015

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2015

Completed
Last Updated

November 20, 2015

Status Verified

November 1, 2015

Enrollment Period

11.3 years

First QC Date

October 15, 2008

Last Update Submit

November 19, 2015

Conditions

Muscular Dystrophy, Oculopharyngeal

Keywords

Oculopharyngeal muscular dystrophySwallowing disorders, dysphagiaPharyngeal propulsionUpper oesophageal sphincterCricopharyngeal muscleAutologous myoblastsAutograftMyotomy of the upper oesophageal sphincterFibroscopy of swallowingVideofluoroscopy of swallowing

Outcome Measures

Primary Outcomes (1)

  • 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

Secondary Outcomes (1)

  • 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

Study Arms (1)

1

EXPERIMENTAL

All patients included

Procedure: Autologous myoblasts transplantation and myotomy

Interventions

Autologous myoblasts transplantation and myotomyPROCEDURE

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)

Also known as: autograft and surgery
1

Eligibility Criteria

Age18 Years - 75 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hospital Tenon

Paris, 75020, France

Location

Related Publications (1)

  • Perie S, Trollet C, Mouly V, Vanneaux V, Mamchaoui K, Bouazza B, Marolleau JP, Laforet P, Chapon F, Eymard B, Butler-Browne G, Larghero J, St Guily JL. Autologous myoblast transplantation for oculopharyngeal muscular dystrophy: a phase I/IIa clinical study. Mol Ther. 2014 Jan;22(1):219-25. doi: 10.1038/mt.2013.155. Epub 2013 Jul 8.

    PMID: 23831596DERIVED

MeSH Terms

Conditions

Muscular Dystrophy, OculopharyngealDeglutition Disorders

Interventions

MyotomyTransplantation, AutologousSurgical Procedures, Operative

Condition Hierarchy (Ancestors)

Muscular DystrophiesMuscular Disorders, AtrophicMuscular DiseasesMusculoskeletal DiseasesNeuromuscular DiseasesNervous System DiseasesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesEsophageal DiseasesGastrointestinal DiseasesDigestive System DiseasesPharyngeal DiseasesOtorhinolaryngologic Diseases

Intervention Hierarchy (Ancestors)

Transplantation

Study Officials

  • Jean Lacau-Saint Guily, MD, PH

    Assistance Publique - Hôpitaux de Paris

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 15, 2008

First Posted

October 16, 2008

Study Start

April 1, 2004

Primary Completion

July 1, 2015

Study Completion

October 1, 2015

Last Updated

November 20, 2015

Record last verified: 2015-11

Locations

FR(1)