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

March 9, 2020 updated by: Neil Lagali

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Sweden
      • Linköping, Sweden, SE-58183
        • Linkoping University Hospital
      • Mölndal, Sweden
        • Sahlgrenska University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Supportive Care
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cacicol20
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.
Device: Cacicol20
Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.
Other Names:
  • RGTA
  • Cacicol
  • RGTA OTR 4120
Placebo Comparator: Placebo
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.
Device: Placebo
Vehicle only in identical packaging, with identical dosage and administration route.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage recovery in subbasal nerve density.
Time Frame: 12 months postoperative
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage recovery in subbasal nerve density.
Time Frame: 6 months postoperative
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
Percentage of epithelial wound closure.
Time Frame: 2 and 7 days postoperative.
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.
Postoperative pain score on the Visual Analog Scale.
Time Frame: Postoperative day 2, 7, month 6, 12
Patient self-assessment using the subjective VAS scale (100 point scale).
Postoperative day 2, 7, month 6, 12
Corneal haze level.
Time Frame: Postoperative month 6, 12
Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale.
Postoperative month 6, 12
Number of postoperative recurrences of erosions.
Time Frame: Postoperative month 12.
As reported by the patient.
Postoperative month 12.
Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
Time Frame: Postoperative month 6, 12
Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry.
Postoperative month 6, 12
Tear production level
Time Frame: Postoperative day 7, month 6, 12
Tear production level (in mm) measured by the Schirmer test without anesthetic.
Postoperative day 7, month 6, 12
Tear quality
Time Frame: Postoperative day 7, month 6, 12
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
Improvement in visual acuity
Time Frame: Postoperative day 7, month 6, 12
Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level.
Postoperative day 7, month 6, 12
Sub basal nerve density measured by clinical in vivo confocal microscopy
Time Frame: Postoperative 6 and 12 months
Sub basal nerve density level measured by clinical in vivo confocal microscopy.
Postoperative 6 and 12 months
Epithelial cell density measured by clinical in vivo confocal microscopy
Time Frame: Postoperative 12 months
Epithelial wing cell density measured by clinical in vivo confocal microscopy.
Postoperative 12 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with adverse events as a measure of safety and tolerability.
Time Frame: From operation day until 12 months postoperative.
Defined as reactions or complications beyond those normally expected after laser corneal surgery. Assessed by the investigator.
From operation day until 12 months postoperative.
Number of patients using supplementary eye treatments.
Time Frame: Operation day until 12 months postoperative.
Use of any supplementary eye treatments.
Operation day until 12 months postoperative.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Neil Lagali

Collaborators

Linkoeping University
Sahlgrenska University Hospital, Sweden
Region Östergötland
Laboratoires Thea

Investigators

  • Study Chair: Sven Jarkman, MD PhD, Region Östergötland

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 1, 2015

Primary Completion (Actual)

December 1, 2017

Study Completion (Actual)

December 1, 2017

Study Registration Dates

First Submitted

February 16, 2015

First Submitted That Met QC Criteria

February 26, 2015

First Posted (Estimate)

February 27, 2015

Study Record Updates

Last Update Posted (Actual)

March 11, 2020

Last Update Submitted That Met QC Criteria

March 9, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2014/465-31

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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