Allogeneic Tissue Engineering (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers in Advanced Stages, Refractory to Conventional (Ophthalmic) Treatment
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
Phase I- II clinical trial to evaluate the feasibility of the method and the absence of relevant side effects derived from product implant.
HYPOTHESIS: Once designed the nanostructured artificial human corneas by the Tissue Engineering Group of the University of Granada, and after evaluating their suitable properties ex vivo and their in vivo utility by means of anterior lamellar keratoplasty in laboratory animals, it is necessary to proceed to clinical evaluation in human patients suffering from severe corneal pathology. The results obtained during pre-clinical study, both in laboratory and in experimental animals, suggest that nanostructured artificial human corneas could help to treat various corneal diseases that occur with any substance loss or serious structural alteration, with no relevant side effects.
| Condition | Intervention | Phase |
|---|---|---|
|
Corneal Ulcer |
Other: Anterior lamellar nanostructured artificial human cornea. |
Phase 1 Phase 2 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment |
| Official Title: | Multicenter Clinical Trial to Evaluate the Safety and Feasibility of an Allogeneic Tissue Engineered Drug (Nanostructured Artificial Human Cornea) in Patients With Corneal Trophic Ulcers Refractory to Conventional Treatment |
- Appearance of adverse events and serious adverse events related to treatment. [ Time Frame: 24 months ] [ Designated as safety issue: Yes ]
- Persistence of the ulcer or regeneration / repair of the corneal stroma. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Visual acuity. [ Time Frame: 24 months ] [ Designated as safety issue: No ]
- Corneal transparency [ Time Frame: 24 months ] [ Designated as safety issue: No ]
| Estimated Enrollment: | 20 |
| Study Start Date: | February 2013 |
| Estimated Study Completion Date: | September 2016 |
| Estimated Primary Completion Date: | September 2016 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
Experimental: Anterior lamellar nanostructured artificial human cornea
Anterior lamellar nanostructured artificial human cornea with allogenic from dead donor and cultured in its inside and allogeneic corneal epithelium cultured in its surface
|
Other: Anterior lamellar nanostructured artificial human cornea.
Implantation of an anterior lamellar nanostructured artificial human cornea with allogeneic cells from dead donors and biomaterials
|
|
No Intervention: Amniotic membrane transplantation
Amniotic membrane transplantation as conventional treatment of corneal trophic ulcers.
|
Detailed Description:
Phase I-II, controlled, randomized, multicenter clinical trial. The total number of patients to be included is 20. In an initial phase, will be included 5 patients sequentially (be subjected to the experimental treatment), with a month and a half safety period between patients.
At random, 5 of these patients will be implanted cornea and 10 control patients will receive conventional treatment of corneal trophic ulcers in advanced stages.
The study population consists of patients with corneal trophic ulcers refractory to conventional treatment attending the ophthalmology departments involved in this research project.
It is estimated that the inclusion period is approximately 24 months, and a follow-up period of 24 months for each patient. Thus the total duration of the study will be about 48 months from the inclusion of the first patient until the end of the follow-up period of the last patient included.
To all patients enrolled in the trial, assigned to the experimental group will proceed to be implanted an anterior lamellar nanostructured artificial cornea with allogeneic cells from dead donors and biomaterials.
The implant of this Advanced Therapy drug will cover defects or structural alterations existing in the affected cornea. In this phase of the study, it is aimed to assess the feasibility of the procedure and the biosafety of the implant once grafted in the patient's cornea.
Patients who are randomized to the control group will be subjected to the usual treatment of their condition, consisting of amniotic membrane transplantation
Once the artificial corneal graft or amniotic membrane transplantation in the affected eye is completed, will proceed with the monitoring and continuous assessment of each subject. For this, it will be used the usual revision methods used for the anterior pole of the eyeball in all hospitals involved in the study.
Main objective: To evaluate the safety, feasibility and evidence of clinical efficacy of an anterior lamellar nanostructured artificial human cornea model, in a group of patients with severe corneal disease, for whom there are currently no effective therapeutic alternative.
Secondary objectives:
- To generate lamellar nanostructured artificial human corneas of allogeneic origin of dead donor, from sclerocorneal limbus and agarose-fibrin biomaterials.
- To implant the nanostructured artificial human corneas of allogeneic origin of dead donor in a group of patients randomized to the experimental group, suffering from severe corneal pathology as a graft in the wound bed.
- To assess Biosecurity the nanostructured artificial human corneas of allogeneic origin of dead donor implanted in patients to rule out relevant adverse reactions.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Patients who give informed consent to participate in the study.
- Presence of corneal ulcers Mackie stage 3 not responding to conventional medical treatment, besides being secondary to any of the specified causes : Riley-Day syndrome, Goldenhar-Gorlin syndrome, Mobius Syndrome, Corneal hypoesthesia family, Diabetes, Multiple Sclerosis, Leprosy, Hypovitaminosis A, Acoustic neuroma, Meningioma, Neuralgia, Aneurysm, Ictus, Neoplasia, Simple herpes, Zoster herpes, Caustic burns, Injury, inflammation, or wear contact lenses, Cataract surgery or keratoplasty, Topical anesthetics abuse, Toxicity of timolol, betaxolol, diclofenac sodium or sulfacetamide, Lattice or granular, Orbital neoplasia.
- Stromal involvement should exist, but with a depth not reaching the Descemet's membrane. The location may be central and / or peripheral.
- No active ocular infection.
- Patients of both sexes over 18 years; no upper age limit exist
- Duration of the disease causing the corneal ulcer equal or superior to six weeks.
Patients with normal laboratory parameters, defined by:
- Leukocytes ≥ 3000
- Neutrophils ≥ 1500
- Platelets ≥ 100,000
- Aspartate Aminotransferase (AST) / Alanine Aminotransferase (ALT) ≤ 1.5 standard range institution
- Creatinine ≤ 1.5 mg / dl
Exclusion Criteria:
- Absence of stromal involvement (eg persistent epithelial defects).
- Corneal Pathology responding properly to standard medical treatments in a shorter period of 3-5 weeks.
- Active ocular infection.
- Positive serology for Hepatitis B virus (HBV), Hepatitis B virus (HCV), Immunodeficiency human virus (HIV) or other coexisting pathology that, in the opinion of the investigator, would prevent from monitoring patients in the trial.
- Pregnant or lactating women or women of childbearing potential not using a proven efficacy contraceptive method. It is described as highly effective contraceptive method that oral contraceptive one (combining estrogen with progestin) or any other such as, for example, an injectable hormonal contraceptive, implantable or patch, intrauterine device (IUD) or surgical sterilization (provided that hormonal contraceptives do not interact with the drug in research
- History of neoplasia except for orbital neoplasia.
- Patients who participated in the last 3 months prior to study inclusion in a clinical trial.
Contacts and Locations| Contact: Ana Cardesa | 0034 955019040 | ana.cardesa@juntadeandalucia.es |
| Spain | |
| University Hospital Puerta del Mar | Not yet recruiting |
| Cádiz, Spain, 11009 | |
| Contact: Belén Hoyos, MD, PhD 660409473 belenhoyossanabria@gmail.com | |
| Principal Investigator: Belén Hoyos, MD, PhD | |
| Sub-Investigator: María Jesús Cruz, MD, PhD | |
| Sub-Investigator: Leticia Royo, MD, PhD | |
| Sub-Investigator: Iratze Zabalza, Zabalza | |
| University Hospital San Cecilio | Not yet recruiting |
| Granada, Spain, 18012 | |
| Contact: Miguel González, MD, PhD 636362952 mgandrades@gmail.com | |
| Principal Investigator: Miguel González, MD, PhD | |
| Sub-Investigator: Daniel Serrano, MD, PhD | |
| Sub-Investigator: Inmaculada Domínguez, MD, PhD | |
| Sub-Investigator: Carmen González, MD, PhD | |
| Sub-Investigator: José Ignacio Muñoz, MD, PhD | |
| Sub-Investigator: José Luis García, MD, PhD | |
| Sub-Investigator: Alberto Villarrubia, MD, PhD | |
| University Hospital Virgen de las Nieves | Not yet recruiting |
| Granada, Spain, 18014 | |
| Contact: Santiago Medialdea, MD, PhD 619271254 santiago.medialdea.sspa@juntadeandalucia.es | |
| Principal Investigator: Santiago Medialdea, MD, PhD | |
| Sub-Investigator: Daniel Martínez, MD, PhD | |
| Sub-Investigator: José Lucena, MD, PhD | |
| University Hospital Virgen de Rocío | Not yet recruiting |
| Sevilla, Spain, 41013 | |
| Contact: Juan Ramón del Trigo, MD, PhD 630926841 deltrigo@telefonica.net | |
| Principal Investigator: Juan Ramón del Trigo, MD, PhD | |
| Sub-Investigator: Ana María Muñoz, MD, PhD | |
| Sub-Investigator: Carmen Vázquez, MD, PhD | |
| University Hospital Virgen Macarena | Not yet recruiting |
| Sevilla, Spain, 41009 | |
| Contact: Ignacio Montero, MD, PhD 955008696 l_morillo@hotmail.com | |
| Sub-Investigator: María Dolores Morillo, MD, PhD | |
| Study Chair: | Miguel González, MD, PhD | University Hospital San Cecilio |
| Study Chair: | Miguel Alaminos, MD, PhD | Universidad de Granada |
More Information
Additional Information:
No publications provided
| Responsible Party: | Fundación Pública Andaluza Progreso y Salud |
| ClinicalTrials.gov Identifier: | NCT01765244 History of Changes |
| Other Study ID Numbers: | CAH/Ulc/2010, 2010-024290-40 |
| Study First Received: | January 9, 2013 |
| Last Updated: | January 9, 2013 |
| Health Authority: | Spain: Agencia Española de Medicamentos y Productos Sanitarios |
Keywords provided by Fundación Pública Andaluza Progreso y Salud:
|
Corneal trophic ulcers |
Additional relevant MeSH terms:
|
Corneal Ulcer Ulcer Eye Infections Infection |
Keratitis Corneal Diseases Eye Diseases Pathologic Processes |
ClinicalTrials.gov processed this record on June 18, 2013