Autologous Platelet-rich Plasma (APRP) in the Treatment of Neurotrophic Keratopathy

May 11, 2023 updated by: Karim Mohamed-Noriega, Universidad Autonoma de Nuevo Leon
Neurotrophic keratopathy (NK) is a condition where the cornea loses its capacity to feel pain and touch. This causes a decrease in the production of certain substances that maintain the integrity of the corneal epithelium (the most superficial layer that covers the cornea). As a result, the cornea cannot heal wounds as fast as it should and this could lead to corneal breakdown. This disease is chronic, meaning that it does not resolve quickly, and the treatments commonly used to manage it (such as artificial tears) take a long time to work, which makes it hard to follow doctor's orders. Autologous platelet-rich plasma is a substance that is obtained from the patient's own blood and it may contain those components that are missing in the tears of people with NK. The purpose of this experiment is to find out whether APRP+PFAT is better than APRP alone or PFAT alone in the treatment of NK. Participants will be randomly assigned to one of three groups: one group will start with APRP, other will start with PFAT and another with PFAT+APRP. The participants will receive each treatment for four weeks, and then the subjects will switch groups and use them for four weeks each (12 weeks total). Investigators will evaluate different parameters that will let us know if your condition is improving. These evaluations will be carried out every four weeks from the start to the end of the protocol. In case of intolerance or adverse effects, treatment will be discontinued.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Neurotrophic keratopathy is characterized by impaired corneal sensitivity that results in a decrease in neurotrophic and epitheliotropic factors that are essential for proper corneal epithelial and ocular surface function. This neurotrophic state halts mitosis and epithelial turnover, which in turn slow down wound healing and lead to epithelial breakdown. Due to the chronicity of this disease, treatment adherence becomes a problem for patients; furthermore, results with conventional treatments such as preservative-free artificial tears are discouraging. Hematopoietic derivatives such as APRP may replace those missing neurotrophic factors and lead to epithelial healing in a faster and more comfortable manner. The objective of this study is to determine if APRP+PFAT is better than autologous platelet-rich plasma (APRP) or preservative-free artificial tears (PFAT) in the treatment of neurotrophic keratopathy. Subjects will be randomly assigned to one of three groups and treatment will be administered for four weeks. After this period, subjects will switch groups and receive the new treatment for four more weeks (cross-over). After this second period is completed, subjects will receive the last treatment for four more weeks. A thorough ophthalmologic evaluation will be performed before starting treatment and every four weeks until completion. Treatment will be discontinued if there are adverse effects or treatment intolerance.

Study Type

Interventional

Enrollment (Anticipated)

39

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Mexico
    • Nuevo Leon
      • Monterrey, Nuevo Leon, Mexico, 64460
        • Recruiting
        • Departamento de Oftalmologia, Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
        • Contact:
        • Principal Investigator:
          • Karim Mohamed-Noriega, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with:

    • Neurotrophic keratopathy diagnosed by esthesiometry (defined as central corneal sensitivity ≤ 3cm using Cochet-Bonnet aesthesiometer).
    • Corneal erosions.
    • Neurotrophic keratopathy secondary to: diabetes mellitus, herpetic keratitis, microbial keratitis sequelae (bacteria, Acanthamoeba, fungi, herpes), limbal stem cell deficiency, chemical or thermic burn sequelae at least 3 months after the accident, ocular trauma with penetrating wound fixed at least 3 months before the trial, surgery carried out at least 3 month before the trial (including keratoplasty, laser in situ keratomileusis, phacoemulsification cataract surgery, extracapsular cataract extraction), adenoviral keratoconjunctivitis resolved at least 3 months the trial.

Exclusion Criteria:

  • Patients diagnosed with:

    • Other ocular surface pathology presenting with corneal erosions but without corneal hyposensitivity.
    • Corneal epithelial defect with or without corneal hyposensitivity.
  • Pregnant women, homeless, migrants.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: PFAT first
1 eyedrop of PFAT every 2 hours in study eye.
Other: PFAT first
Week 1 to week 4: one eyedrop of PFAT (preservative-free artificial tears) every 2 hours. Week 5 to week 8: one eyedrop of APRP (autologous plasma rich platelet) every 2 hours. Week 9 to week 12: one eyedrop of PFAT and APRP every 2 hours.
Experimental: APRP first
1 eyedrop of APRP every 2 hours in study eye.
Other: APRP first
Week 1 to week 4: one eyedrop of APRP every 2 hours. Week 5 to week 8: one eyedrop of PFAT every 2 hours. Week 9 to week 12: one eyedrop of PFAT and APRP every 2 hours.
Experimental: APRP+PFAT first
1 eyedrop of PFAT and APRP every 2 hours in study eye.
Other: PFAT first
Week 1 to week 4: one eyedrop of PFAT (preservative-free artificial tears) every 2 hours. Week 5 to week 8: one eyedrop of APRP (autologous plasma rich platelet) every 2 hours. Week 9 to week 12: one eyedrop of PFAT and APRP every 2 hours.
Other: APRP first
Week 1 to week 4: one eyedrop of APRP every 2 hours. Week 5 to week 8: one eyedrop of PFAT every 2 hours. Week 9 to week 12: one eyedrop of PFAT and APRP every 2 hours.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in corneal staining
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Change in corneal epithelial damage will be measured using corneal staining with fluorescein dye and the NEI grading scale.
from the beginning of the treatment and every 4 weeks until week 12.
Change in corneal sensitivity
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Change in corneal sensitivity will be measured using Cochet-Bonnet aesthesiometer.
from the beginning of the treatment and every 4 weeks until week 12.
Tear break-up time (TBUT)
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Tear break up time will be assessed using fluorescein dye, measuring break up time in seconds. A result >10 seconds will be considered normal, a result <10 seconds will be considered pathological.
from the beginning of the treatment and every 4 weeks until week 12.
Ocular Surface Disease Index (OSDI)
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Ocular surface symptoms will be assessed by the Ocular Surface Disease Index (OSDI). The OSDI questionnaire consists of 12 questions that assess dry eye symptoms and their effects on vision related function. The questionnaire is divided in 3 subscales: ocular symptoms, vision-related function, and environmental triggers. Patients are asked to rate their responses on a 0 to 4 scale where 0 represents "none of the time", 1 "some of the time", 2 "half of the time", 3 "most of the time", and 4 "all of the time". The total score is calculated using the following formula: ([sum of scores for all questions answered x 100] / [total number of questions answered x 4]). Lower scores represent a better outcome.
from the beginning of the treatment and every 4 weeks until week 12.
Tear osmolarity.
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Tear osmolarity is one of tear inflammation biomarkers. Tear osmolarity will be performed with Tear Lab Osmolarity System, a result of 308 milliosmol (mOsm)/L or higher indicates pathological result.
from the beginning of the treatment and every 4 weeks until week 12.
Schirmer test with anesthesia
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Tear production will be measured by Schirmer test with anesthesia. The Schirmer test with anesthesia >15 mm is consider normal.
from the beginning of the treatment and every 4 weeks until week 12.
Quality of life questionnaire (National Eye Institute Visual Function Questionnaire-25)
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Quality of life as assessed by the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). The NEI VFQ-25 questionnaire consists of 25 questions that assess the effect of visual impairment on the patient's quality of life. The 25-item questionnaire gives a score on a scale of 0 to 100, where 0 is the worst score and 100 is the best score. Higher scores represent a better outcome.
from the beginning of the treatment and every 4 weeks until week 12.
Best corrected visual acuity
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Best corrected visual acuity will be assessed using Snellen cards. Measurements will be converted to LogMar values for statistical analysis.
from the beginning of the treatment and every 4 weeks until week 12.
Frequency of adverse events.
Time Frame: from the beginning of the treatment and every 4 weeks until week 12.
Frequency of adverse events will assessed for security and effectiveness of the treatment during the ophthalmic evaluation.
from the beginning of the treatment and every 4 weeks until week 12.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Universidad Autonoma de Nuevo Leon

Collaborators

Hospital Universitario Dr. Jose E. Gonzalez

Investigators

  • Principal Investigator: Karim Mohamed-Noriega, M.D., Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 1, 2020

Primary Completion (Anticipated)

November 1, 2024

Study Completion (Anticipated)

December 1, 2024

Study Registration Dates

First Submitted

October 15, 2020

First Submitted That Met QC Criteria

October 26, 2020

First Posted (Actual)

October 27, 2020

Study Record Updates

Last Update Posted (Actual)

May 15, 2023

Last Update Submitted That Met QC Criteria

May 11, 2023

Last Verified

May 1, 2022

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • OF14-004

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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