A Phase I/IIa Study for the Treatment of Uveitis With Iontophoresis

Uveitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT00499551
• Other study ID #: Iontophoresis001
• Status: Withdrawn
• Phase: Phase 1/Phase 2
• First received: July 9, 2007
• Last updated: July 8, 2008
• Start date: September 2007
• Est. completion date: September 2009

Study information

• Verified date: July 2008
• Source: Asociación para Evitar la Ceguera en México
• Contact: n/a
• Is FDA regulated: No
• Health authority: Mexico: National Institute of Public Health, Health Secretariat
• Study type: Interventional

Clinical Trial Summary

The multiple properties of the corticosteroids over the inflammatory response, make them first line drugs for the treatment of several ocular inflammatory disorders of different etiologies. In order to diminish the corticosteroids severe systemic adverse effects, the local administration is preferred. Iontophoresis already has been used in a successful way for the administration of corticosteroids. Clinical or histopathological injuries due to the use of transcleral CCI have not been observed. being successful the administration of methylprednisolone by means of this system in previous studies. The objective is to evaluate the tolerance, security and effectiveness of this treatment, using a new generation device.

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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 30
• Est. completion date: September 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 15 Years to 90 Years

Eligibility

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 Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Uveitis

Intervention

Device:
• Iontophoresis second generation Eyegate II device

Locations

Country	Name	City	State
Mexico	Asociación para Evitar la Ceguera en Mexico	Mexico	DF

Sponsors (1)

Lead Sponsor	Collaborator
Asociación para Evitar la Ceguera en México

Country where clinical trial is conducted

Mexico, 

References & Publications (15)

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. — View Citation

Barza M, Peckman C, Baum J. Transscleral iontophoresis of cefazolin, ticarcillin, and gentamicin in the rabbit. Ophthalmology. 1986 Jan;93(1):133-9. — View Citation

Barza M, Peckman C, Baum J. Transscleral iontophoresis of gentamicin in monkeys. Invest Ophthalmol Vis Sci. 1987 Jun;28(6):1033-6. — View Citation

Benson H. Permeability of the cornea to topically applied drugs. Arch Ophthalmol. 1974 Apr;91(4):313-27. Review. — View Citation

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. — View Citation

Cole HP, Stallman J. Diamon DJ. High Dose Intravitreal Dexamethasone for Infections Endophthalmitis. Invest Ophthalmol Visc Sci. 1989;30:509-512.

Lachaud JP. [Considerations on the use of corticoids by ionization in certain ocular diseases]. Bull Soc Ophtalmol Fr. 1965 Jan;65(1):84-9. French. — View Citation

Lam TT, Edward DP, Zhu XA, Tso MO. Transscleral iontophoresis of dexamethasone. Arch Ophthalmol. 1989 Sep;107(9):1368-71. — View Citation

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. Erratum in: Graefes Arch Clin Exp Ophthalmol 1992;230(2):199. — View Citation

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. — View Citation

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. — View Citation

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. Review. — View Citation

Stanbury RM, Graham EM. Systemic corticosteroid therapy--side effects and their management. Br J Ophthalmol. 1998 Jun;82(6):704-8. Review. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	to assess the tolerance, security and effectiveness in the treatment of different intraocular inflammatory disease		two years
Secondary	To establish the Iontophoresis utility in the drug administration in the treatment of the IID		two years
Secondary	To establish the effectiveness of the CCI with Dexamethasone in the IID control		two years
Secondary	To establish the security of the Dexamethasone administration with CCI in the treatment of the IID		two years
Secondary	To establish the time in which the control of the ocular inflammation is succeed when using the CCI with Dexamethasone.		two years