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出境医 / 临床实验 / Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)

Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)

Study Description
Brief Summary:

Keratoconus is characterized by a thinning of the cornea, which causes a decrease in visual acuity due to astigmatism.

Publications suggest that keratoconus is linked to chronic inflammation (increase in pro-inflammatory cytokines and metalloproteinases (MMP). Direct epithelial-stromal interactions (D-ESI) have a role in the induction of metalloproteinases (MMP) and the differentiation of fibroblasts into myofibroblasts via an EMMPRIN membrane glycoprotein (extracellular matrix membran MMP inducer - CD 147). On a healthy cornea, EMMPRIN's effects are prevented by a lack of contact between epithelial and stromal cells through a basement membrane, which is altered in the keratoconus The hypothesis is that stromal thinning of the keratoconus could be related to increased expression of EMMPRIN by epithelial and stromal cells (resulting in increased MMP synthesis), with a preponderance at the most deformed areas.

The main objective is to demonstrate a transformation of fibroblasts to myofibroblasts in the corneal stroma of keratoconus patients.


Condition or disease Intervention/treatment
Keratoconus Procedure: Corneal sampling

Study Design
Layout table for study information
Study Type : Observational
Actual Enrollment : 0 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)
Actual Study Start Date : November 1, 2019
Actual Primary Completion Date : May 12, 2020
Actual Study Completion Date : May 12, 2020
Arms and Interventions
Group/Cohort Intervention/treatment
Cases
Patients suffering from keratoconus and requiring a first optical corneal transplant
Procedure: Corneal sampling
Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.

Controls
Patients with an indication of orbital exenteration operation due to an orbital tumor
Procedure: Corneal sampling
Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.

Outcome Measures
Primary Outcome Measures :
  1. Comparison of alpha-SMA's (Smooth Muscle Actin) messenger RNA expression evaluated by quantitative PCR (RT-qPCR) in corneal stroma in keratoconus patients compared to non-keratoconus controls [ Time Frame: 12 hours ]

Eligibility Criteria
Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Keratoconus patients requiring first optical corneal transplantation and controls with indication of orbital exenteration due to an orbital tumor.
Criteria

Inclusion Criteria:

  • For the cases :

    - Suffering from keratoconus and requiring a first optical corneal transplant

  • For the controls:

    • Orbital exenteration operation due to an orbital tumor
    • Absence of any anomaly of the ocular surface observed during the slit lamp examination at the last preoperative consultation

Exclusion Criteria:

  • For the cases:

    • Keratoconus patient requiring a tectonic corneal transplant
    • Known pregnancy, or breastfeeding
  • For the controls:

    • History of orbital radiotherapy
    • History of corneal surgery
    • History of corneal surface tumour
    • Eye surface abnormality noted in the preoperative period
    • Known keratoconus
    • Known pregnancy, or breastfeeding
    • Secondary exclusion if a keratoconus is diagnosed during the immunohistochemical analysis by visualization of Bowman membrane interruption
Contacts and Locations

No Contacts or Locations Provided

Tracking Information
First Submitted Date June 11, 2019
First Posted Date June 19, 2019
Last Update Posted Date May 14, 2020
Actual Study Start Date November 1, 2019
Actual Primary Completion Date May 12, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 18, 2019)
Comparison of alpha-SMA's (Smooth Muscle Actin) messenger RNA expression evaluated by quantitative PCR (RT-qPCR) in corneal stroma in keratoconus patients compared to non-keratoconus controls [ Time Frame: 12 hours ]
Original Primary Outcome Measures Same as current
Change History
Current Secondary Outcome Measures Not Provided
Original Secondary Outcome Measures Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus
Official Title Myofibroblastic Transformation Secondary to Epithelial-stromal Interactions in the Keratoconus (MYKE)
Brief Summary

Keratoconus is characterized by a thinning of the cornea, which causes a decrease in visual acuity due to astigmatism.

Publications suggest that keratoconus is linked to chronic inflammation (increase in pro-inflammatory cytokines and metalloproteinases (MMP). Direct epithelial-stromal interactions (D-ESI) have a role in the induction of metalloproteinases (MMP) and the differentiation of fibroblasts into myofibroblasts via an EMMPRIN membrane glycoprotein (extracellular matrix membran MMP inducer - CD 147). On a healthy cornea, EMMPRIN's effects are prevented by a lack of contact between epithelial and stromal cells through a basement membrane, which is altered in the keratoconus The hypothesis is that stromal thinning of the keratoconus could be related to increased expression of EMMPRIN by epithelial and stromal cells (resulting in increased MMP synthesis), with a preponderance at the most deformed areas.

The main objective is to demonstrate a transformation of fibroblasts to myofibroblasts in the corneal stroma of keratoconus patients.

Detailed Description Not Provided
Study Type Observational
Study Design Observational Model: Case-Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Not Provided
Sampling Method Non-Probability Sample
Study Population Keratoconus patients requiring first optical corneal transplantation and controls with indication of orbital exenteration due to an orbital tumor.
Condition Keratoconus
Intervention Procedure: Corneal sampling
Corneal samples will be taken during corneal transplants for cases and orbital exenterations for controls. The mRNA (messenger ribonucleic acid) will be extracted and a retrotranscription will be made to obtain cDNA (complementary DNA). A qPCR (quantitative polymerase chain reaction) will be able to quantify the expression of alpha-SMA, MMP 1-2-3 and 9, and EMMPRIN.
Study Groups/Cohorts
  • Cases
    Patients suffering from keratoconus and requiring a first optical corneal transplant
    Intervention: Procedure: Corneal sampling
  • Controls
    Patients with an indication of orbital exenteration operation due to an orbital tumor
    Intervention: Procedure: Corneal sampling
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Withdrawn
Actual Enrollment
 (submitted: May 12, 2020)
0
Original Estimated Enrollment
 (submitted: June 18, 2019)
60
Actual Study Completion Date May 12, 2020
Actual Primary Completion Date May 12, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • For the cases :

    - Suffering from keratoconus and requiring a first optical corneal transplant

  • For the controls:

    • Orbital exenteration operation due to an orbital tumor
    • Absence of any anomaly of the ocular surface observed during the slit lamp examination at the last preoperative consultation

Exclusion Criteria:

  • For the cases:

    • Keratoconus patient requiring a tectonic corneal transplant
    • Known pregnancy, or breastfeeding
  • For the controls:

    • History of orbital radiotherapy
    • History of corneal surgery
    • History of corneal surface tumour
    • Eye surface abnormality noted in the preoperative period
    • Known keratoconus
    • Known pregnancy, or breastfeeding
    • Secondary exclusion if a keratoconus is diagnosed during the immunohistochemical analysis by visualization of Bowman membrane interruption
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Not Provided
Removed Location Countries  
 
Administrative Information
NCT Number NCT03990740
Other Study ID Numbers EGN_2017_22
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Fondation Ophtalmologique Adolphe de Rothschild
Study Sponsor Fondation Ophtalmologique Adolphe de Rothschild
Collaborators Not Provided
Investigators Not Provided
PRS Account Fondation Ophtalmologique Adolphe de Rothschild
Verification Date May 2020

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