Clinical trial NCT04604834: Autologous Platelet-rich Plasma (APRP) in the Treatment of Neurotrophic Keratopathy
Official title: Autologous Platelet-rich Plasma (APRP) in the Treatment of Neurotrophic Keratopathy
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Neurotrophic Keratopathy
Keywords: Autologous PRP
Neurotrophic keratopathy
Autologous platelet-rich plasma
Lead sponsor: Universidad Autonoma de Nuevo Leon
Sponsor class: OTHER
Collaborators: name: Hospital Universitario Dr. Jose E. Gonzalez
First posted: 2020-10-27
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Subjects will be selected based on inclusion and exclusion criteria. A thorough ophthalmologic evaluation will be carried out before starting any treatment (baseline). Subjects will be randomly assigned to one of the treatment groups and receive the corresponding treatment for 4 weeks. At the end of week 4, subjects will switch treatment groups (crossover) and receive the new treatment for 4 more weeks. At the end of week 8, subjects will start the last treatment for 4 more weeks. Ophthalmologic evaluations will be performed every 4 weeks.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in corneal staining
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Change in corneal sensitivity
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Tear break-up time (TBUT)
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Ocular Surface Disease Index (OSDI)
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Tear osmolarity.
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Schirmer test with anesthesia
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Quality of life questionnaire (National Eye Institute Visual Function Questionnaire-25)
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Best corrected visual acuity
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
measure: Frequency of adverse events.
timeFrame: from the beginning of the treatment and every 4 weeks until week 12.
Secondary outcomes:
Other outcomes:
Locations:
city: Monterrey
country: Mexico
facility: Departamento de Oftalmologia, Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
state: Nuevo Leon
Study officials:
affiliation: Departamento de Oftalmologia, Hospital Universitario Dr. Jose Eleuterio Gonzalez
name: Karim Mohamed-Noriega, M.D.
role: PRINCIPAL_INVESTIGATOR
References: