Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy

Corneal Dystrophy, Epithelial Basement Membrane Clinical Trial

— CACICOL-PTK  

Official title:

Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy of the Anterior Cornea: A Randomized Double-Blinded Placebo-Controlled Study

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02373397
• Other study ID #: 2014/465-31
• Status: Terminated
• Phase: N/A
• Start date: March 2015
• Est. completion date: December 2017

Study information

• Verified date: March 2020
• Source: Region Östergötland
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 40
• Est. completion date: December 2017
• Est. primary completion date: December 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Corneal Dystrophy, Epithelial Basement Membrane
• Corneal Erosions
• Epithelial Recurrent Erosion Dystrophy

Intervention

Device:
• Cacicol20
Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.
• Placebo
Vehicle only in identical packaging, with identical dosage and administration route.

Locations

Country	Name	City	State
Sweden	Linköping University Hospital	Linköping
Sweden	Sahlgrenska University Hospital	Mölndal

Sponsors (5)

Lead Sponsor	Collaborator
Neil Lagali	Laboratoires Thea, Linkoeping University, Region Östergötland, Sahlgrenska University Hospital, Sweden

Country where clinical trial is conducted

Sweden, 

References & Publications (7)

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. — View 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. French. — View Citation

De Monchy I, Labbé 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. — View 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. — View 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. — View 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. — View Citation

Meddahi A, Alexakis C, Papy D, Caruelle JP, Barritault D. Heparin-like polymer improved healing of gastric and colic ulceration. J Biomed Mater Res. 2002 Jun 5;60(3):497-501. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of patients with adverse events as a measure of safety and tolerability.	Defined as reactions or complications beyond those normally expected after laser corneal surgery. Assessed by the investigator.	From operation day until 12 months postoperative.
Other	Number of patients using supplementary eye treatments.	Use of any supplementary eye treatments.	Operation day until 12 months postoperative.
Primary	Percentage recovery in subbasal nerve density.	Degree of corneal subbasal nerve regeneration at one year postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy.	12 months postoperative
Secondary	Percentage recovery in subbasal nerve density.	Degree of corneal subbasal nerve regeneration at 6 months postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy.	6 months postoperative
Secondary	Percentage of epithelial wound closure.	A drop of sodium fluorescein liquid is applied to the cornea, and a digital photograph is taken at high magnification with a clinical slit lamp biomicroscope, using a blue illumination lamp. Area of open wound is measured from photographs and expressed as a percentage of the total treated area.	2 and 7 days postoperative.
Secondary	Postoperative pain score on the Visual Analog Scale.	Patient self-assessment using the subjective VAS scale (100 point scale).	Postoperative day 2, 7, month 6, 12
Secondary	Corneal haze level.	Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale.	Postoperative month 6, 12
Secondary	Number of postoperative recurrences of erosions.	As reported by the patient.	Postoperative month 12.
Secondary	Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.	Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry.	Postoperative month 6, 12
Secondary	Tear production level	Tear production level (in mm) measured by the Schirmer test without anesthetic.	Postoperative day 7, month 6, 12
Secondary	Tear quality	Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking.	Postoperative day 7, month 6, 12
Secondary	Improvement in visual acuity	Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level.	Postoperative day 7, month 6, 12
Secondary	Sub basal nerve density measured by clinical in vivo confocal microscopy	Sub basal nerve density level measured by clinical in vivo confocal microscopy.	Postoperative 6 and 12 months
Secondary	Epithelial cell density measured by clinical in vivo confocal microscopy	Epithelial wing cell density measured by clinical in vivo confocal microscopy.	Postoperative 12 months