Autologous Adipose-Derived Adult Stem Cell Implantation for Corneal Diseases (ADASCs-CT-CD)

NCT05279157 | Completed Phase 2

• 2 other identifiers: EI17-005232018-000523-14
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Cellular therapy of the corneal stroma with implantation of mesenchymal stem cells derived from autologous adipose tissue with or without a carrier (scaffold) composed by decellularized human donor corneal stroma is used in patients with corneal diseases such as corneal dystrophies, and keratoconus. For this purpose, the study planned to assess the enhancement of visual acuity, pachymetric, and aberrometric parameters with implantation of autologous mesenchymal adipose tissue-derived adult stem cells (ADASCs) alone, 120 µm thickness of decellularized or recellularized laminas with ADASCs. Three groups will be included in the study: (1) Implantation of a single dose of ADASCs alone without scaffold. (2) Implantation of decellularized human corneal lamina without ADASCs. (3) Implantation of the recellularized human corneal lamina with ADASCs.

Conditions

Ophthalmological Disorder; Corneal Dystrophy; Treatment; Therapy; Keratoconus

Keywords

Regenerative medicine; Corneal bioengineering; Stem cell therapy; Keratoconus; Adipose-derived adult stem cells (ADASCs); Keratocytes; Corneal confocal microscopy; Advanced corneal therapy

Outcome Measures

Primary Outcomes (1)

• Improvement in best-corrected distance visual acuity (BCDVA).

  Best-corrected visual acuity (BCDVA) will be studied in Snellen charts by Logmar and the corresponding equivalent in decimal scale.

  at 12 months

Secondary Outcomes (3)

• Increase in corneal thickness.

  at 12 months

• Refractive changes

  at 12 months

• Improvement in anterior corneal surface regularity

  at 12 months

Study Arms (3)

ADASCs Group

EXPERIMENTAL

5 patients, who will receive adipose tissue mesenchymal stem cells in a single dose as study treatment

Procedure: Implantation; Procedure: Lipoaspiration

Acellular laminas group

EXPERIMENTAL

5 patients, who will receive decellularized corneal laminas as treatment medication

Procedure: Implantation

ADASCs recellularized laminas group

EXPERIMENTAL

5 patients, who will receive adipose tissue mesenchymal cells combined with decellularized corneal laminas as study treatment in a single intervention

Procedure: Implantation; Procedure: Lipoaspiration

Interventions

Implantation PROCEDURE

Procedure: Implantation The ophthalmologist will carry out the implantation of the ADASCs cells with or without scaffold in the intrastromal cornea of the patient

Also known as: corneal implantation

ADASCs Group; ADASCs recellularized laminas group; Acellular laminas group

Lipoaspiration PROCEDURE

Procedure: Lipoaspiration The patient will have a liposuction surgery from which the autologous ADASCs implant in the cornea will be obtained. Procedure: Implantation The ophthalmologist will carry out the implantation of the ADASCs with or without scaffold in the intrastromal cornea of the patient

Also known as: corneal implantation

ADASCs Group; ADASCs recellularized laminas group

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients affected by corneal stromal dystrophies of any type, but particularly keratoconus, showing clear evidence in the ophthalmic examination of the presence and clear expression of the disease and loss of vision as a result of it
• Patients with best-corrected visual acuity less than 0.6
• Absence of chronic or recurrent inflammation in the anterior segment and on the ocular surface.
• Patient suitable to undergo corneal graft surgery under local anesthesia, from a medical point of view.
• Pre-surgical analysis of serum biochemistry and normal hematology.
• Serology for Human Immunodeficiency Virus (HIV), Hepatitis B (HBV), and Hepatitis C (HCV) negative.
• No history of malignancy.
• Normal chest x-ray (Rx).
• Normal urinalysis.
• Normal thyroid exam

You may not qualify if:

• Dense and extensive corneal stromal scars with severe involvement of the visual axis and located in the pupillary area, causing a decrease in the best corrected vision to levels of 0.1 or less.
• Distance corrected vision with glasses of 0.7 or greater.
• Extreme corneal thinning with risk of perforation.
• Infection.
• Previous corneal surgeries.
• Moderate or severe dry eye.
• Moderate or severe chronic inflammatory pathology of the ocular surface.
• Previous eye surgery other than cataract.
• Presence of cataract or other severe opacity of the transparent media of the eye that could prevent adequate examination of the fundus.
• Other ophthalmic comorbidity such as glaucoma or uveitis or any that requires the chronic use of topical ocular medication.
• Known and severe coagulation abnormalities.
• Any medical condition that may interfere with causing serious adverse effects during the study.
• Presence of active or inactive corneal neovascularization (CNV) in the eye to be treated
• Any immunodeficiency or systemic autoimmune disease
• Any current or intermittent immunosuppressive therapy or low-dose corticosteroids.

Sponsors & Collaborators

• Vissum, Instituto Oftalmológico de Alicante: lead
• Universidad Miguel Hernandez de Elche: collaborator
• Instituto de Salud Carlos III: collaborator

Study Sites (1)

Jorge L. Alio

Alicante, 03016, Spain

Location

Related Publications (9)

• Alio Del Barrio JL, El Zarif M, de Miguel MP, Azaar A, Makdissy N, Harb W, El Achkar I, Arnalich-Montiel F, Alio JL. Cellular Therapy With Human Autologous Adipose-Derived Adult Stem Cells for Advanced Keratoconus. Cornea. 2017 Aug;36(8):952-960. doi: 10.1097/ICO.0000000000001228.

  PMID: 28486314 RESULT

• Alio Del Barrio JL, El Zarif M, Azaar A, Makdissy N, Khalil C, Harb W, El Achkar I, Jawad ZA, de Miguel MP, Alio JL. Corneal Stroma Enhancement With Decellularized Stromal Laminas With or Without Stem Cell Recellularization for Advanced Keratoconus. Am J Ophthalmol. 2018 Feb;186:47-58. doi: 10.1016/j.ajo.2017.10.026. Epub 2017 Dec 13.

  PMID: 29103962 RESULT

• Alio Del Barrio JL, Arnalich-Montiel F, De Miguel MP, El Zarif M, Alio JL. Corneal stroma regeneration: Preclinical studies. Exp Eye Res. 2021 Jan;202:108314. doi: 10.1016/j.exer.2020.108314. Epub 2020 Oct 24.

  PMID: 33164825 RESULT

• Alio JL, Alio Del Barrio JL, El Zarif M, Azaar A, Makdissy N, Khalil C, Harb W, El Achkar I, Jawad ZA, De Miguel MP. Regenerative Surgery of the Corneal Stroma for Advanced Keratoconus: 1-Year Outcomes. Am J Ophthalmol. 2019 Jul;203:53-68. doi: 10.1016/j.ajo.2019.02.009. Epub 2019 Feb 15.

  PMID: 30772348 RESULT

• El Zarif M, Alio JL, Alio Del Barrio JL, Abdul Jawad K, Palazon-Bru A, Abdul Jawad Z, De Miguel MP, Makdissy N. Corneal Stromal Regeneration Therapy for Advanced Keratoconus: Long-term Outcomes at 3 Years. Cornea. 2021 Jun 1;40(6):741-754. doi: 10.1097/ICO.0000000000002646.

  PMID: 33591032 RESULT

• El Zarif M, A Jawad K, Alio Del Barrio JL, A Jawad Z, Palazon-Bru A, de Miguel MP, Saba P, Makdissy N, Alio JL. Corneal Stroma Cell Density Evolution in Keratoconus Corneas Following the Implantation of Adipose Mesenchymal Stem Cells and Corneal Laminas: An In Vivo Confocal Microscopy Study. Invest Ophthalmol Vis Sci. 2020 Apr 9;61(4):22. doi: 10.1167/iovs.61.4.22.

  PMID: 32301973 RESULT

• El Zarif M, Alio Del Barrio JL, Arnalich-Montiel F, De Miguel MP, Makdissy N, Alio JL. Corneal Stroma Regeneration: New Approach for the Treatment of Cornea Disease. Asia Pac J Ophthalmol (Phila). 2020 Dec;9(6):571-579. doi: 10.1097/APO.0000000000000337.

  PMID: 33181549 RESULT

• El Zarif M, Alio JL, Alio Del Barrio JL, De Miguel MP, Abdul Jawad K, Makdissy N. Corneal Stromal Regeneration: A Review of Human Clinical Studies in Keratoconus Treatment. Front Med (Lausanne). 2021 Feb 23;8:650724. doi: 10.3389/fmed.2021.650724. eCollection 2021.

  PMID: 33708786 RESULT

• Alio JL. Corneal regeneration: How can we make further progress in corneal surgery with advanced therapies to avoid corneal substitution: ESCRS Binkhorst Medal Lecture 2023. J Cataract Refract Surg. 2025 Nov 1;51(11):1026-1033. doi: 10.1097/j.jcrs.0000000000001745.

  PMID: 41126474 DERIVED

MeSH Terms

Conditions

Eye Diseases; Corneal Dystrophies, Hereditary; Keratoconus

Interventions

Drug Implants

Condition Hierarchy (Ancestors)

Corneal Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Delayed-Action Preparations; Dosage Forms; Pharmaceutical Preparations

Study Officials

• Jorge L Alio, MD, PhD

  Universidad Miguel Hernandez, Elche, Spain

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Masking Details: Patients who agree to participate in the study and sign the informed consent will be randomized to enter one of the three groups in a 1: 1: 1 ratio. For this, a randomization scheme will be used that will be unknown to the patient, the center staff, and the promoter staff who intervene directly in the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In this study, 15 evaluable patients affected by corneal stromal dystrophies of any type (particularly keratoconus) will be included in 3 different groups. Ten patients will be included in the two experimental groups and five in the control group with cell-free treatment (5 patients per group and a total of 3 groups)

Study Record Dates

• First Submitted: December 17, 2021
• First Posted: March 15, 2022
• Study Start: April 19, 2022
• Primary Completion: February 5, 2023
• Study Completion: February 5, 2023
• Last Updated: May 6, 2023

Record last verified: 2023-05

Locations

ES (1)