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Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft (TTT-PT-DOP)

Primary Purpose

Muscular Dystrophy, Oculopharyngeal, Ptosis

Status
Terminated
Phase
Phase 2
Locations
France
Study Type
Interventional
Intervention
Myoblast autologous graft
Sponsored by
University Hospital, Caen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Muscular Dystrophy, Oculopharyngeal

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Male or female ( with suitable contraception) over 18 years of age 75
  • OPMD confirmed by genetic diagnosis ( gene mutation PABPN1 by triplet expansion GCG)
  • OPMD with ptosis
  • Obtaining informed consent signed

Exclusion Criteria:

  • Evolutionary contagious infectious pathology
  • Inflammatory diseases
  • Any other neuromuscular disease
  • Malignant tumor pathology of history
  • Renal impairment ( creatinine clearance < 60ml / min)
  • Hepatic insufficiency
  • Pregnant woman confirmed by a dosing B-HCG or lactating
  • Inability to perform a muscle biopsy
  • Preparation of myoblasts uncommitted to step 2nd release
  • Inability to follow up to 36 months
  • Refusal to sign the consent form
  • No Social Security

Sites / Locations

  • CHU Caen

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Myoblast autologous graft

Arm Description

30 million autologous myoblasts in 6 intramuscular injections

Outcomes

Primary Outcome Measures

Improvement of ptosis
The improvement in ptosis is considered by measuring the opening of the lid gap ( OFP) , the gaze straight ahead and no inclination of the head, the eye untreated and treated before and after treatment at 12 month.

Secondary Outcome Measures

acuity
Measure of visual acuity ( without lifting the lid manually and without head tilt ) according Monoyer scale ,
Goldmann Visual Field
neck pain with Visual Analaogue Scale
Tolerance of the sampling procedure and transplantation, swelling (yes / no)
Tolerance of the sampling procedure and transplantation : visual analogue scale Pain about the procedure
Tolerance of collection of the seat and transplantation: hematoma (yes / no )
fever
strength of the levator muscle of the upper eyelid
This is assessed by measuring the travel of the free edge of the upper eyelid between the eyes down and look up blocking the frontal muscle (photos and films) . Normal Range : 15 to 17 mm. Very impaired in patients with DOP .

Full Information

First Posted
March 8, 2016
Last Updated
November 23, 2020
Sponsor
University Hospital, Caen
Collaborators
University Hospital, Rouen, Rennes University Hospital, Centre Hospitalier Universitaire, Amiens, University Hospital, Lille, University Hospital, Brest, Groupe Hospitalier Pitie-Salpetriere
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1. Study Identification

Unique Protocol Identification Number
NCT02878694
Brief Title
Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
Acronym
TTT-PT-DOP
Official Title
Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft
Study Type
Interventional

2. Study Status

Record Verification Date
November 2020
Overall Recruitment Status
Terminated
Why Stopped
insufficient recruitment
Study Start Date
November 14, 2019 (Actual)
Primary Completion Date
October 9, 2020 (Actual)
Study Completion Date
October 9, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Caen
Collaborators
University Hospital, Rouen, Rennes University Hospital, Centre Hospitalier Universitaire, Amiens, University Hospital, Lille, University Hospital, Brest, Groupe Hospitalier Pitie-Salpetriere

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Interventional , multicenter , comparative study. One eye receiving the cells and the contralateral eye as a negative control . If effectiveness following review of the primary endpoint and the advice of an independent expert committee , the experimental treatment will be offered to the patient to the contralateral eyelid. Objective is to restore muscle function levator muscle of the upper eyelid by providing a registry of autologous myoblasts from a non- clinically affected muscle .
Detailed Description
Muscular dystrophy oculopharyngeal ( OPMD ) is an autosomal dominant inherited myopathy manifested as selective involvement of the levator muscles of the upper eyelids , head of ptosis, and muscles of the intersection pharyngolaryngeal originally disorders swallowing. Ptosis can be treated with surgery ( shortening of the levator muscle ), but the disease continues to evolve , relapses occur , necessitating another intervention , which is the suspension of the eyelid to the frontal muscle that can cause corneal complications by imperfect lid closure . Main objective is to restore muscle function levator muscle of the upper eyelid by providing a registry of autologous myoblasts from a non- clinically affected muscle . A study on the same model was conducted in patients in ENT OPMD crossroads of muscles with encouraging results , 12/12 patients had improved quality of life and no degradation of swallowing was observed in 10 / 12 patients. This is an interventional study , multicenter, comparative , one eye receiving the cells and the contralateral eye as a negative control . If effectiveness following review of the primary endpoint and the advice of an independent expert committee , the experimental treatment will be offered to the patient to the contralateral eyelid. Seven centers are associated with this project as inclusion and assessment center. Patients are referred by different clinical sites in Caen ophthalmology department which will be performed pre-transplant assessment, the collection of donor myoblast muscle graft and part tracking. The expected duration is 3 years (2 years of inclusion and evaluation of the primary endpoint at 1 year) for inclusion of 10 patients. The safety of autologous myoblast transplantation has been shown in several directions with promising efficacy results. They will be produced by the unit of Biotherapy Rouen University Hospital (Prof. O. Boyer), who currently leads a test with these cells (ClinicalTrials.gov, myoblast for Anal Incontinence (MIAS), NCT01523522, 24 patients were provided in Protocol was included in July 2014, at 6 months follow up of the last patient is expected in January 2015) and authorized the production of advanced therapy medicinal products prepared punctually (ANSM). In this study, different successive steps: Step of including: patient aged 18 to 75, verification of the diagnosis of the disease, evaluation balance ptosis (measurements, photographs, films), obtaining consent, Muscle biopsy of a healthy muscle to cell amplification, an outpatient basis, under local anesthesia, 3 to 4 weeks before transplantation, Transplant myoblasts by multiple intramuscular injections (6), under local anesthesia. Longitudinal microscarifications be made superficially injected into muscles to stimulate muscle regeneration. Intramuscular injection of myoblasts will be in the levator muscle of the upper lid 6 in equidistant points, each injection containing 5 million cells. These injections will be made in muscle mass over an area of about 5 cm2, ranging between 6 and 20 mm above the tarsus to be in the thick muscle area. It is intended to be injected into the eye to treat randomized a total of 30 million myoblasts. This protocol is based on the one used for correction of ENT disorders within several PHRC under the responsibility of Professor Sophie Périé. The doses used for the myoblast transplantation in the pharyngeal constrictor muscles were adapted to the levator muscle of the eyelid. Follow-up visits for 3 years for each patient: The first year, to evaluation of the primary endpoint visit to 8 days to a month, then every 3 months Out protocol and up to 3 years after administration of the cells every 6 months (this monitoring will be carried out as part of standard care). These visits evaluate the effectiveness of the transplant on different objective measurements on both eyes (eyelid opening slot in the gaze straight ahead; levator muscle strength of the upper eyelid, visual benefit: measurement of visual acuity measurement visual field), and the profit on neck pain. The tours include a side effect detection examination (local inflammatory phenomena, palpable lumps). In the end, this landmark trial for the new F.H.U. SURFACE dealing with regenerative medicine in the head and neck, the investigators expect an improvement in the quality of the levator of the upper eyelid muscles deficient with a correction of ptosis in patients.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Muscular Dystrophy, Oculopharyngeal, Ptosis

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Myoblast autologous graft
Arm Type
Experimental
Arm Description
30 million autologous myoblasts in 6 intramuscular injections
Intervention Type
Biological
Intervention Name(s)
Myoblast autologous graft
Intervention Description
30 million autologous myoblasts in 6 intramuscular injections No treatment in the second eye
Primary Outcome Measure Information:
Title
Improvement of ptosis
Description
The improvement in ptosis is considered by measuring the opening of the lid gap ( OFP) , the gaze straight ahead and no inclination of the head, the eye untreated and treated before and after treatment at 12 month.
Time Frame
baseline and 12 months
Secondary Outcome Measure Information:
Title
acuity
Description
Measure of visual acuity ( without lifting the lid manually and without head tilt ) according Monoyer scale ,
Time Frame
12 months
Title
Goldmann Visual Field
Time Frame
12 months
Title
neck pain with Visual Analaogue Scale
Time Frame
12 months
Title
Tolerance of the sampling procedure and transplantation, swelling (yes / no)
Time Frame
baseline
Title
Tolerance of the sampling procedure and transplantation : visual analogue scale Pain about the procedure
Time Frame
baseline
Title
Tolerance of collection of the seat and transplantation: hematoma (yes / no )
Time Frame
baseline
Title
fever
Time Frame
baseline
Title
strength of the levator muscle of the upper eyelid
Description
This is assessed by measuring the travel of the free edge of the upper eyelid between the eyes down and look up blocking the frontal muscle (photos and films) . Normal Range : 15 to 17 mm. Very impaired in patients with DOP .
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Male or female ( with suitable contraception) over 18 years of age 75 OPMD confirmed by genetic diagnosis ( gene mutation PABPN1 by triplet expansion GCG) OPMD with ptosis Obtaining informed consent signed Exclusion Criteria: Evolutionary contagious infectious pathology Inflammatory diseases Any other neuromuscular disease Malignant tumor pathology of history Renal impairment ( creatinine clearance < 60ml / min) Hepatic insufficiency Pregnant woman confirmed by a dosing B-HCG or lactating Inability to perform a muscle biopsy Preparation of myoblasts uncommitted to step 2nd release Inability to follow up to 36 months Refusal to sign the consent form No Social Security
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Françoise CF Chapon, PhD
Organizational Affiliation
CHU Caen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Olivier BO Boyer, PhD
Organizational Affiliation
CHU Rouen
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Frederic MF Mouriaux, PhD
Organizational Affiliation
CHU Rennes
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Sophie PS Perie, PhD
Organizational Affiliation
APHP
Official's Role
Study Chair
Facility Information:
Facility Name
CHU Caen
City
Caen
ZIP/Postal Code
14000
Country
France

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Treatment of Ptosis to Muscular Dystrophy Oculopharyngeal by Myoblast Autologous Graft

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