Corneal Dystrophy, Epithelial Basement MembraneCACICOL-PTKNCT02373397
Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy
A study testing Cacicol20 in people with Corneal Dystrophy, Epithelial Basement Membrane and Epithelial Recurrent Erosion Dystrophy, run by Neil Lagali at 2 sites in Sweden.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Corneal Dystrophy, Epithelial Basement Membrane, Epithelial Recurrent Erosion Dystrophy, Corneal Erosions
- What is being tested?
- Cacicol20
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesSweden
- Study dates
- Mar 2015to Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country.
Sweden2 sites
Linköping University Hospital
Linköping, SE-58183
Sahlgrenska University Hospital
Mölndal
About this study
Official title: 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.
Read the 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.
- Conditions
- Corneal Dystrophy, Epithelial Basement Membrane, Epithelial Recurrent Erosion Dystrophy, Corneal Erosions
- Being tested
- Cacicol20, Placebo
- Keywords
- Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery
- Medical subject headings
- Corneal dystrophy, epithelial basement membrane, Epithelial Recurrent Erosion Dystrophy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cacicol20Device
Also called RGTA, Cacicol, RGTA OTR 4120
Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing.
PlaceboDevice
Vehicle only in identical packaging, with identical dosage and administration route.
| Study group | Role | What they receive |
|---|---|---|
| Cacicol20 | Experimental | 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. Receives: Device: Cacicol20 |
| Placebo | Placebo comparator | 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. Receives: Device: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 12 months postoperative
Secondary outcomes (11)
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.
Measured: 6 months postoperative
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.
Measured: 2 and 7 days postoperative.
Postoperative pain score on the Visual Analog Scale.
Patient self-assessment using the subjective VAS scale (100 point scale).
Measured: Postoperative day 2, 7, month 6, 12
Corneal haze level.
Corneal haze measured microscopically by clinical in vivo confocal microscopy using a semi-quantitative grading scale.
Measured: Postoperative month 6, 12
Number of postoperative recurrences of erosions.
As reported by the patient.
Measured: Postoperative month 12.
Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
Central corneal mechanical touch sensitivity in mm measured by Cochet-Bonnet esthesiometry.
Measured: Postoperative month 6, 12
Tear production level
Tear production level (in mm) measured by the Schirmer test without anesthetic.
Measured: Postoperative day 7, month 6, 12
Tear quality
Tear break up time (in seconds) timed by slit lamp biomicroscopic observation after instillation of sodium fluorescein and induction of blinking.
Measured: Postoperative day 7, month 6, 12
Improvement in visual acuity
Distance corrected visual acuity improvement measured in Snellen lines gained/lost relative to preoperative level.
Measured: Postoperative day 7, month 6, 12
Sub basal nerve density measured by clinical in vivo confocal microscopy
Sub basal nerve density level measured by clinical in vivo confocal microscopy.
Measured: Postoperative 6 and 12 months
Epithelial cell density measured by clinical in vivo confocal microscopy
Epithelial wing cell density measured by clinical in vivo confocal microscopy.
Measured: Postoperative 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2015 (estimated)
- Study startMar 2015
- Primary completionDec 2017
- Study completionDec 2017
Why it stopped: Study terminated due to poor patient recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Corneal Dystrophy, Epithelial Basement MembraneStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Neil Lagali
- Sponsor type
- University, hospital or other
- Collaborators
- Region Östergötland, Linkoeping University, Sahlgrenska University Hospital, Laboratoires Thea
- Responsible party
- Sponsor-investigator, Neil Lagali, Region Östergötland
- Investigators
- Sven Jarkman, MD PhD, Study chair, Region Östergötland
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02373397
- Sponsor's protocol ID
- 2014/465-31
- Acronym
- CACICOL-PTK
- Status last verified
- Mar 2020
- First submitted
- 16 Feb 2015
- Last updated
- 11 Mar 2020
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 11920675Chebbi 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.
PubMed 18641578Lagali 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.
PubMed 19407024Germundsson 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.
PubMed 24569577Cejkova 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.
PubMed 24105332De 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.
PubMed 22015067Kymionis 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.
PubMed 24937169
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Cacicol20® in Corneal Wound Healing and Nerve Regeneration After Phototherapeutic Keratectomy of the Anterior Cornea: A Randomized Double-Blinded Placebo-Controlled Study
- ClinicalTrials.gov ID
- NCT02373397
- Acronym / sponsor ID
- CACICOL-PTK / 2014/465-31
- Conditions
- Corneal Dystrophy, Epithelial Basement Membrane, Epithelial Recurrent Erosion Dystrophy, Corneal Erosions
- Keywords
- Wound healing, nerve regeneration, re-epithelialization, corneal epithelium, laser corneal surgery
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated due to poor patient recruitment
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Neil LagaliUniversity, hospital or other
- Collaborators
- Region Östergötland, Linkoeping University, Sahlgrenska University Hospital, Laboratoires Thea
- Study start
- Mar 2015 (actual)
- Primary completion
- Dec 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 27 Feb 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cacicol20 | Experimental | Device: Cacicol20Instillation 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. |
| Placebo | Placebo comparator | Device: PlaceboInstillation 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (11 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cacicol20Also: RGTA, Cacicol, RGTA OTR 4120Investigational device, regenerating agent, single-use doses, topical eye drops. Indicated for corneal wound healing. | Device | Cacicol20 |
| PlaceboVehicle only in identical packaging, with identical dosage and administration route. | Device | Placebo |
Primary outcome
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.
11 secondary outcomes
Percentage recovery in subbasal nerve density.
Time frame: 6 months postoperative
Percentage of epithelial wound closure.
Time frame: 2 and 7 days postoperative.
Postoperative pain score on the Visual Analog Scale.
Time frame: Postoperative day 2, 7, month 6, 12
Corneal haze level.
Time frame: Postoperative month 6, 12
Number of postoperative recurrences of erosions.
Time frame: Postoperative month 12.
Ocular surface sensitivity measured by Cochet-Bonnet esthesiometry.
Time frame: Postoperative month 6, 12
Tear production level
Time frame: Postoperative day 7, month 6, 12
Tear quality
Time frame: Postoperative day 7, month 6, 12
Improvement in visual acuity
Time frame: Postoperative day 7, month 6, 12
Sub basal nerve density measured by clinical in vivo confocal microscopy
Time frame: Postoperative 6 and 12 months
Epithelial cell density measured by clinical in vivo confocal microscopy
Time frame: Postoperative 12 months
Results and safety
The study was stopped early (reason given: Study terminated due to poor patient recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
- Background: PubMed 11920675Meddahi 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.
- Background: PubMed 18641578Chebbi 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.
- Background: PubMed 19407024Lagali 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.
- Background: PubMed 24569577Germundsson 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.
- Background: PubMed 24105332Cejkova 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.
- Background: PubMed 22015067De 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.
- Background: PubMed 24937169Kymionis 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Sven Jarkman, MD PhD study chair
Region Östergötland
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Cacicol20 in people with Corneal Dystrophy, Epithelial Basement Membrane and Epithelial Recurrent Erosion Dystrophy, run by Neil Lagali at 2 sites in Sweden.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Study terminated due to poor patient recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage recovery in subbasal nerve density. (time frame: 12 months postoperative). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02373397, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2020.