Clinical trial NCT02373397: Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy
Official title: Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy of the Anterior Cornea: A Randomized Double-Blinded Placebo-Controlled Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Corneal Dystrophy, Epithelial Basement Membrane
Epithelial Recurrent Erosion Dystrophy
Corneal Erosions
Keywords: Wound healing
nerve regeneration
re-epithelialization
corneal epithelium
laser corneal surgery
Lead sponsor: Region Östergötland
Sponsor class: OTHER
Collaborators: name: Region Östergötland
name: Linkoeping University
name: Sahlgrenska University Hospital
name: Laboratoires Thea
First posted: 2015-02-27
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The objective of this clinical study is to test the efficacy of CACICOL20® (RGTA OTR 4120) in improving wound healing and nerve regeneration in the anterior cornea, in a patient population undergoing therapeutic laser treatment for corneal dystrophy or recurrent corneal erosions.

Detailed description: Patients undergoing various surgical treatments of the cornea often suffer from a neural deficit, due to nerves being severed or removed completely during surgery. This can result in pain, impaired epithelial wound healing, reduced tear production, symptoms of dry eye, and loss of ocular surface sensitivity/blink reflex. In addition, surgical wound healing can be accompanied by undesirable formation of scar tissue, which can limit postoperative visual acuity. The investigators' prior clinical experience with patients having undergone surgery of the anterior cornea is that neural recovery is slow and incomplete, while in certain situations scar tissue can form and limit the visual recovery.

In this context, CACICOL20®, a regenerative agent approved for use in healing corneal wounds, presents an interesting opportunity for improving postoperative corneal nerve regeneration and a potentially more rapid restoration of the extracellular matrix environment postoperatively, which can lead to improved neural and visual outcomes.

The investigators will therefore evaluate the efficacy of CACICOL20® in a randomized, double-blinded clinical study, to evaluate its ability to promote corneal nerve regeneration, epithelial wound healing, and ocular surface recovery postoperatively.

Upon inclusion and signing of informed consent, patients undergo preoperative examination. Upon satisfying study criteria, patients are randomized to either treatment or placebo group. Group identity is masked to subjects and to investigators (double-blind). Subjects then undergo therapeutic laser treatment of the cornea in a single clinic, followed by instillation of treatment or placebo in the form of 3 eye drops total (to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery).

Postoperative eye examinations are conducted on days 2 and 7 and at month 6 and 12. Examinations include clinical measurement of various eye and corneal wound healing parameters.

Eligibility criteria: Inclusion Criteria:

* Signed and dated informed consent,
* Male or female aged ≥ 18 years,
* Patient with recurrent erosions or epithelial dystrophies indicated for treatment by phototherapeutic keratectomy of the anterior cornea

Exclusion Criteria:

* In the affected eye: prior corneal surgery
* In either eye: active ocular infection, glaucoma, or ocular hypertension
* General history judged by the investigator to be incompatible with the study (life-threatening patient condition).
* Known allergic hypersensitivity history to Poly(carboxyMethylGlucoseSulfate) or dextran.
* Inability of patient to understand the study procedures and thus inability to give informed consent.
* Participation in another clinical study within the last 3 months.
* Already included once in this study (can only be included for one treated eye)

Specific exclusion criteria for women

* Known pregnancy (if uncertain pregnancy test will be performed)
* Lactation
* Women of childbearing potential without an effective method of contraception (oral contraceptive, intra-uterine device, subcutaneous contraceptive implant, vaginal ring) or women not hysterectomised, post-menopausal or surgically sterilized

Primary outcomes:
measure: Percentage recovery in subbasal nerve density.
timeFrame: 12 months postoperative
Secondary outcomes:
measure: Percentage recovery in subbasal nerve density.
timeFrame: 6 months postoperative
measure: Percentage of epithelial wound closure.
timeFrame: 2 and 7 days postoperative.
measure: Postoperative pain score on the Visual Analog Scale.
timeFrame: Postoperative day 2, 7, month 6, 12
measure: Corneal haze level.
timeFrame: Postoperative month 6, 12
measure: Number of postoperative recurrences of erosions.
timeFrame: Postoperative month 12.
measure: Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
timeFrame: Postoperative month 6, 12
measure: Tear production level
timeFrame: Postoperative day 7, month 6, 12
measure: Tear quality
timeFrame: Postoperative day 7, month 6, 12
measure: Improvement in visual acuity
timeFrame: Postoperative day 7, month 6, 12
measure: Sub basal nerve density measured by clinical in vivo confocal microscopy
timeFrame: Postoperative 6 and 12 months
measure: Epithelial cell density measured by clinical in vivo confocal microscopy
timeFrame: Postoperative 12 months
Other outcomes:
measure: Number of patients with adverse events as a measure of safety and tolerability.
timeFrame: From operation day until 12 months postoperative.
measure: Number of patients using supplementary eye treatments.
timeFrame: Operation day until 12 months postoperative.
Locations:
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Mölndal
country: Sweden
facility: Sahlgrenska University Hospital
Study officials:
affiliation: Region Östergötland
name: Sven Jarkman, MD PhD
role: STUDY_CHAIR
References:
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citation: Chebbi CK, Kichenin K, Amar N, Nourry H, Warnet JM, Barritault D, Baudouin C. [Pilot study of a new matrix therapy agent (RGTA OTR4120) in treatment-resistant corneal ulcers and corneal dystrophy]. J Fr Ophtalmol. 2008 May;31(5):465-71. doi: 10.1016/s0181-5512(08)72462-8. French.
citation: Lagali N, Germundsson J, Fagerholm P. The role of Bowman's layer in corneal regeneration after phototherapeutic keratectomy: a prospective study using in vivo confocal microscopy. Invest Ophthalmol Vis Sci. 2009 Sep;50(9):4192-8. doi: 10.1167/iovs.09-3781. Epub 2009 Apr 30.
citation: Germundsson J, Lagali N. Pathologically reduced subbasal nerve density in epithelial basement membrane dystrophy is unaltered by phototherapeutic keratectomy treatment. Invest Ophthalmol Vis Sci. 2014 Mar 25;55(3):1835-41. doi: 10.1167/iovs.13-12533.
citation: Cejkova J, Olmiere C, Cejka C, Trosan P, Holan V. The healing of alkali-injured cornea is stimulated by a novel matrix regenerating agent (RGTA, CACICOL20): a biopolymer mimicking heparan sulfates reducing proteolytic, oxidative and nitrosative damage. Histol Histopathol. 2014 Apr;29(4):457-78. doi: 10.14670/HH-29.10.457. Epub 2013 Oct 9.
citation: De Monchy I, Labbe A, Pogorzalek N, Gendron G, M'Garrech M, Kaswin G, Labetoulle M. [Management of herpes zoster neurotrophic ulcer using a new matrix therapy agent (RGTA): A case report]. J Fr Ophtalmol. 2012 Mar;35(3):187.e1-6. doi: 10.1016/j.jfo.2011.09.002. Epub 2011 Oct 19. French.
citation: Kymionis GD, Liakopoulos DA, Grentzelos MA, Diakonis VF, Klados NE, Tsoulnaras KI, Tsilimbaris MK, Pallikaris IG. Combined topical application of a regenerative agent with a bandage contact lens for the treatment of persistent epithelial defects. Cornea. 2014 Aug;33(8):868-72. doi: 10.1097/ICO.0000000000000169.