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Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy (CACICOL-PTK)

Primary Purpose

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

Status
Terminated
Phase
Not Applicable
Locations
Sweden
Study Type
Interventional
Intervention
Cacicol20
Placebo
Sponsored by
Neil Lagali
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Corneal Dystrophy, Epithelial Basement Membrane focused on measuring Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Linköping University Hospital
  • Sahlgrenska University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Cacicol20

Placebo

Arm Description

Instillation of Cacicol20 eye drops after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery.

Instillation of placebo eye drops (vehicle missing the active ingredient) after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
Postoperative pain score on the Visual Analog Scale.
Patient self-assessment using the subjective VAS scale (100 point scale).
Corneal haze level.
Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale.
Number of postoperative recurrences of erosions.
As reported by the patient.
Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry.
Tear production level
Tear production level (in mm) measured by the Schirmer test without anesthetic.
Tear quality
Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking.
Improvement in visual acuity
Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level.
Sub basal nerve density measured by clinical in vivo confocal microscopy
Sub basal nerve density level measured by clinical in vivo confocal microscopy.
Epithelial cell density measured by clinical in vivo confocal microscopy
Epithelial wing cell density measured by clinical in vivo confocal microscopy.

Full Information

First Posted
February 16, 2015
Last Updated
March 9, 2020
Sponsor
Neil Lagali
Collaborators
Region Östergötland, Linkoeping University, Sahlgrenska University Hospital, Sweden, Laboratoires Thea
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1. Study Identification

Unique Protocol Identification Number
NCT02373397
Brief Title
Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2020
Overall Recruitment Status
Terminated
Why Stopped
Study terminated due to poor patient recruitment
Study Start Date
March 2015 (Actual)
Primary Completion Date
December 2017 (Actual)
Study Completion Date
December 2017 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Neil Lagali
Collaborators
Region Östergötland, Linkoeping University, Sahlgrenska University Hospital, Sweden, Laboratoires Thea

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Corneal Dystrophy, Epithelial Basement Membrane, Epithelial Recurrent Erosion Dystrophy, Corneal Erosions
Keywords
Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cacicol20
Arm Type
Experimental
Arm Description
Instillation of Cacicol20 eye drops after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Instillation of placebo eye drops (vehicle missing the active ingredient) after laser corneal surgery. 3 eye drops total, to be given once immediately after surgery, once 2 days after surgery, and a final time 4 days after surgery.
Intervention Type
Device
Intervention Name(s)
Cacicol20
Other Intervention Name(s)
RGTA, Cacicol, RGTA OTR 4120
Intervention Description
Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.
Intervention Type
Device
Intervention Name(s)
Placebo
Intervention Description
Vehicle only in identical packaging, with identical dosage and administration route.
Primary Outcome Measure Information:
Title
Percentage recovery in subbasal nerve density.
Description
Degree of corneal subbasal nerve regeneration at one year postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy.
Time Frame
12 months postoperative
Secondary Outcome Measure Information:
Title
Percentage recovery in subbasal nerve density.
Description
Degree of corneal subbasal nerve regeneration at 6 months postoperative, compared to preoperative level, as measured by clinical laser-scanning in vivo confocal microscopy.
Time Frame
6 months postoperative
Title
Percentage of epithelial wound closure.
Description
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.
Time Frame
2 and 7 days postoperative.
Title
Postoperative pain score on the Visual Analog Scale.
Description
Patient self-assessment using the subjective VAS scale (100 point scale).
Time Frame
Postoperative day 2, 7, month 6, 12
Title
Corneal haze level.
Description
Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale.
Time Frame
Postoperative month 6, 12
Title
Number of postoperative recurrences of erosions.
Description
As reported by the patient.
Time Frame
Postoperative month 12.
Title
Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
Description
Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry.
Time Frame
Postoperative month 6, 12
Title
Tear production level
Description
Tear production level (in mm) measured by the Schirmer test without anesthetic.
Time Frame
Postoperative day 7, month 6, 12
Title
Tear quality
Description
Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking.
Time Frame
Postoperative day 7, month 6, 12
Title
Improvement in visual acuity
Description
Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level.
Time Frame
Postoperative day 7, month 6, 12
Title
Sub basal nerve density measured by clinical in vivo confocal microscopy
Description
Sub basal nerve density level measured by clinical in vivo confocal microscopy.
Time Frame
Postoperative 6 and 12 months
Title
Epithelial cell density measured by clinical in vivo confocal microscopy
Description
Epithelial wing cell density measured by clinical in vivo confocal microscopy.
Time Frame
Postoperative 12 months
Other Pre-specified Outcome Measures:
Title
Number of patients with adverse events as a measure of safety and tolerability.
Description
Defined as reactions or complications beyond those normally expected after laser corneal surgery. Assessed by the investigator.
Time Frame
From operation day until 12 months postoperative.
Title
Number of patients using supplementary eye treatments.
Description
Use of any supplementary eye treatments.
Time Frame
Operation day until 12 months postoperative.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sven Jarkman, MD PhD
Organizational Affiliation
Region Östergötland
Official's Role
Study Chair
Facility Information:
Facility Name
Linköping University Hospital
City
Linköping
ZIP/Postal Code
SE-58183
Country
Sweden
Facility Name
Sahlgrenska University Hospital
City
Mölndal
Country
Sweden

12. IPD Sharing Statement

Citations:
PubMed Identifier
11920675
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. doi: 10.1002/jbm.1293.
Results Reference
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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.
Results Reference
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PubMed Identifier
19407024
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.
Results Reference
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PubMed Identifier
24569577
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.
Results Reference
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PubMed Identifier
24105332
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.
Results Reference
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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.
Results Reference
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Results Reference
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Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy

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