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

This study has been withdrawn prior to enrollment.
(The drug needed for the study is not available in Mexico anymore.)
Sponsor:
Information provided by:
Asociación para Evitar la Ceguera en México
ClinicalTrials.gov Identifier:
NCT00499551
First received: July 9, 2007
Last updated: July 8, 2008
Last verified: July 2008
  Purpose

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.


Condition Intervention Phase
Uveitis
Device: Iontophoresis second generation Eyegate II device
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Asociación para Evitar la Ceguera en México:

Primary Outcome Measures:
  • to assess the tolerance, security and effectiveness in the treatment of different intraocular inflammatory disease [ Time Frame: two years ]

Secondary Outcome Measures:
  • To establish the Iontophoresis utility in the drug administration in the treatment of the IID [ Time Frame: two years ]
  • To establish the effectiveness of the CCI with Dexamethasone in the IID control [ Time Frame: two years ]
  • To establish the security of the Dexamethasone administration with CCI in the treatment of the IID [ Time Frame: 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 ]

Estimated Enrollment: 30
Study Start Date: September 2007
Estimated Study Completion Date: September 2009
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.

  Eligibility

Ages Eligible for Study:   15 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00499551

Locations
Mexico
Asociación para Evitar la Ceguera en Mexico
Mexico, DF, Mexico, 04030
Sponsors and Collaborators
Asociación para Evitar la Ceguera en México
Investigators
Principal Investigator: Hugo Quiroz-Mercado, MD Asociación para Evitar la Ceguera en Mexico
Principal Investigator: Lourdes Arellanes, MD Asociación para Evitar la Ceguera en Mexico
Study Director: Raul Velez-Montoya, MD Asociación para Evitar la Ceguera en Mexico
  More Information

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

ClinicalTrials.gov Identifier: NCT00499551     History of Changes
Other Study ID Numbers: Iontophoresis001
Study First Received: July 9, 2007
Last Updated: July 8, 2008
Health Authority: Mexico: National Institute of Public Health, Health Secretariat

Keywords provided by Asociación para Evitar la Ceguera en México:
Anterior Uveitis
Posterior Uveitis
Intermediate Uveitis
Panuveitis
Iontophoresis
Dexamethasone

Additional relevant MeSH terms:
Uveitis
Chorioretinitis
Uveal Diseases
Eye Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis
Dexamethasone
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Central Nervous System Agents
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Antineoplastic Agents, Hormonal
Antineoplastic Agents

ClinicalTrials.gov processed this record on September 30, 2014