- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00499551
A Phase I/IIa Study for the Treatment of Uveitis With Iontophoresis
A Phase I/IIa Study of the Treatment of None-Infectious Anterior, Intermediate, Posterior and Panuveitis, With the Use of Dexamethasone Delivered by a Iontophoresis Device
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The multiple properties of the corticosteroids on the inflammatory response, make them a first line election in the treatment of several ocular inflammatory disorders of different etiologies. Within its properties we can mention: the reestablishment of the vascular permeability, decrease of the cellular infiltrated and the exudation of fibrin, alteration of the activity of monocytes and neutrophils, decrease the proliferation of fibroblasts and endothelial cells and diminish the neovascularization post inflammation (1). For that reason, not only they diminish the inflammatory reaction, but they also diminish the formation of permanent scar, that often is responsible for the visual loss (2,3).
The most severe systemic adverse effects of the corticosteroids are: systemic hyperglicemy, the formation of gastric ulcers, avascular necrosis to of the head of the femur, suppression of the hypothalamus-pituitary adrenal axis, arterial hypertension among others (21,22). In order to diminish the severe systemic adverse effects of the corticosteroids, the local administration is preferred (4). The subconjunctival injection or topical instillation, reaches effective concentrations in the anterior chamber (5-7) whereas to reach these concentrations in the posterior segment it requires a systemic, intravitreous or periocular administration (8-11). Generally it require multiple injections, which produces patient discomfort. In addition, after periocular administration, just a small fraction of the drug penetrates the eye, whereas the rest is systemically absorbed, reason why the systemic adverse effects are not avoided.
Iontophoresis already has been successful used for the administration of corticosteroids, reaching high and lasting concentrations in both segments of the eye. (12-13). Remaining with effective concentrations up to 40 to 60 hours after the administration (23). But, Because focal chorioretinal injuries have been described, with the use of transcleral Iontophoresis, using current of high densities (14-18), this method has not gain a space in the current clinical practice. It has been previously demonstrated that the Controlled Column Iontophoresis (CCI Eyegate, Optis France SA) was as effective as the intraperitoneal administration of Dexamethasone for the treatment of the anterior and posterior uveitis induced by endotoxins (19). Through control of the electrical parameters and using safer settings, clinical or histopathological injuries due to the use of transcleral CCI have not been observed (20). The results of a pre-clinical study, in which methylprednisolone succinate by means of CCI was administered, demonstrated to be a safe method, reporting high and lasting intraocular concentrations.
In addition, a study in France was elaborated, that included 89 patients with different intraocular inflammatory diseases. Such as corneal graft rejections, previous uveitis, postoperative endophthalmitis, macular edema and inflammations of the posterior segment. For the evaluation of the security and effectiveness of the administration of methylprednisolone by means of CCI. The patients were enlisted if they required periocular or systemic treatment due to the failure of maximal topical therapy. The average of treatment with Iontophoresis was of 2,7 +/- 0,9 (1-5), with an current intensity of 1,2 to 2mA and duration of 2 to 5 minutes of each treatment.
A significant increase of conjunctival hyperemia was observed, subsequent to each CCI, which spontaneous resolved. There were no related adverse Effects. Still more, it was observed an increase of the visual acuity and decrease of the clinical inflammation in this group of patients. No of the patients loss vision and the inflammation biomarkers, taken like a whole, continued improving up to 30 days after the treatment.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
DF
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Mexico, DF, Mexico, 04030
- Asociación Para Evitar la Ceguera en México
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Clinical history of, none-infectious anterior, intermediate, posterior or panuveitis, with or without associate systemic disease, like: Vogt Koyanagi Harada, Wegener Granulomatosis, Systemic erythematous Lupus, Behçet disease, etc.
- Requirement or with current topical treatment with steroids (more than every 6 hours), needs acute or chronic treatment with oral, intravenous, periocular or intravitreous corticosteroids or immunosuppressive agents for the control of the disease.
- Best Corrected Visual Acuity in the worse eye of 20/40 to 20/800 in ETDRS record.
- Patients with good mydriasis and no significant ocular opacities.
- Patients who do not plan elective surgery.
Exclusion Criteria:
- Infectious, pos-traumatic, Fuchs or self-limited uveitis. Patients with Diagnosis of glaucoma or ocular hypertension (greater than 25mmHg).
- Diagnosis or suspects ocular or central nervous system lymphoma. Patients with only one eye.
- Associated optical Neuritis of any etiology.
- Severe injuries in the eyelids or in the ocular surface that prevent the application of the electrode.
- Well-known allergy to the Dexamethasone.
- Toxoplasma scar or vitreous hemorrhage.
- Corneal injuries of herpetic origin or with suspicion of being herpetic.
- Patients with poor mydriasis, significant ocular opacities that prevents the evaluation of the posterior pole or the follow-up studies.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Non-Randomized
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
to assess the tolerance, security and effectiveness in the treatment of different intraocular inflammatory disease
Time Frame: two years
|
two years
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To establish the Iontophoresis utility in the drug administration in the treatment of the IID
Time Frame: two years
|
two years
|
To establish the effectiveness of the CCI with Dexamethasone in the IID control
Time Frame: two years
|
two years
|
To establish the security of the Dexamethasone administration with CCI in the treatment of the IID
Time Frame: two years
|
two years
|
To establish the time in which the control of the ocular inflammation is succeed when using the CCI with Dexamethasone.
Time Frame: two years
|
two years
|
Collaborators and Investigators
Investigators
- Principal Investigator: Hugo Quiroz-Mercado, MD, Asociación Para Evitar la Ceguera en México
- Principal Investigator: Lourdes Arellanes, MD, Asociación Para Evitar la Ceguera en México
- Study Director: Raul Velez-Montoya, MD, Asociación Para Evitar la Ceguera en México
Publications and helpful links
General Publications
- Lam TT, Edward DP, Zhu XA, Tso MO. Transscleral iontophoresis of dexamethasone. Arch Ophthalmol. 1989 Sep;107(9):1368-71. doi: 10.1001/archopht.1989.01070020438050.
- Weijtens O, Schoemaker RC, Cohen AF, Romijn FP, Lentjes EG, van Rooij J, van Meurs JC. Dexamethasone concentration in vitreous and serum after oral administration. Am J Ophthalmol. 1998 May;125(5):673-9. doi: 10.1016/s0002-9394(98)00003-8.
- Weijtens O, van der Sluijs FA, Schoemaker RC, Lentjes EG, Cohen AF, Romijn FP, van Meurs JC. Peribulbar corticosteroid injection: vitreal and serum concentrations after dexamethasone disodium phosphate injection. Am J Ophthalmol. 1997 Mar;123(3):358-63. doi: 10.1016/s0002-9394(14)70131-x.
- Bodker FS, Ticho BH, Feist RM, Lam TT. Intraocular dexamethasone penetration via subconjunctival or retrobulbar injections in rabbits. Ophthalmic Surg. 1993 Jul;24(7):453-7.
- Cole HP, Stallman J. Diamon DJ. High Dose Intravitreal Dexamethasone for Infections Endophthalmitis. Invest Ophthalmol Visc Sci. 1989;30:509-512.
- Schulman JA, Peyman GA. Intravitreal corticosteroids as an adjunct in the treatment of bacterial and fungal endophthalmitis. A review. Retina. 1992;12(4):336-40. doi: 10.1097/00006982-199212040-00007.
- Stanbury RM, Graham EM. Systemic corticosteroid therapy--side effects and their management. Br J Ophthalmol. 1998 Jun;82(6):704-8. doi: 10.1136/bjo.82.6.704.
- Leibowitz HM, Kupferman A. Periocular injection of corticosteroids: an experimental evaluation of its role in the treatment of corneal inflammation. Arch Ophthalmol. 1977 Feb;95(2):311-4. doi: 10.1001/archopht.1977.04450020112019.
- MCCARTNEY HJ, DRYSDALE IO, GORNALL AG, BASU PK. AN AUTORADIOGRAPHIC STUDY OF THE PENETRATION OF SUBCONJUNCTIVALLY INJECTED HYDROCORTISONE INTO THE NORMAL AND INFLAMED RABBIT EYE. Invest Ophthalmol. 1965 Jun;4:297-302. No abstract available.
- Benson H. Permeability of the cornea to topically applied drugs. Arch Ophthalmol. 1974 Apr;91(4):313-27. doi: 10.1001/archopht.1974.03900060323017. No abstract available.
- Barry A, Rousseau A, Babineau LM. The penetration of steroids into the rabbit's vitreous, choroid and retina following retrobulbar injection. I. Can J Ophthalmol. 1969 Oct;4(4):365-9. No abstract available.
- Lachaud JP. [Considerations on the use of corticoids by ionization in certain ocular diseases]. Bull Soc Ophtalmol Fr. 1965 Jan;65(1):84-9. No abstract available. French.
- Lam TT, Fu J, Tso MO. A histopathologic study of retinal lesions inflicted by transscleral iontophoresis. Graefes Arch Clin Exp Ophthalmol. 1991;229(4):389-94. doi: 10.1007/BF00170699. Erratum In: Graefes Arch Clin Exp Ophthalmol 1992;230(2):199.
- Barza M, Peckman C, Baum J. Transscleral iontophoresis of cefazolin, ticarcillin, and gentamicin in the rabbit. Ophthalmology. 1986 Jan;93(1):133-9. doi: 10.1016/s0161-6420(86)33780-1.
- Barza M, Peckman C, Baum J. Transscleral iontophoresis of gentamicin in monkeys. Invest Ophthalmol Vis Sci. 1987 Jun;28(6):1033-6.
Study record dates
Study Major Dates
Study Start
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- Iontophoresis001
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