Cyclosporin Implant to Treat Uveitis

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001737
First received: November 3, 1999
Last updated: March 3, 2008
Last verified: March 2004
  Purpose

This study will evaluate the safety and effectiveness of a sustained-release cyclosporin implant to treat uveitis, a sight-threatening eye inflammation caused by an immune system abnormality. Previous studies in humans have shown that, taken by mouth, the drug cyclosporin is effective in treating chronic uveitis.

Uveitis may require long-term treatment with potent immune-suppressing drugs, such as cyclosporin, cyclophosphamide, methotrexate, azathioprine or steroids. Taken systemically (by mouth or injection), however, these drugs can do serious damage to the kidneys, liver or lungs, and can raise blood pressure and lower blood cell counts. Because of this, some patients cannot or will not use these medicines.

This small pilot study will evaluate the safety, and to some extent effectiveness, of cyclosporin delivered directly into the eye, to try to prevent harmful side effects. In animal studies, sustained-release cyclosporin implants did not cause the severe side effects seen with systemic use of the drug. Some animals developed opacity of the lens and slowed retinal responses, both of which reversed when the drug was stopped. Earlier animal studies of cyclosporin injected directly into the eye reduced inflammation that had been produced experimentally.

Patients with uveitis who have active inflammation and poor vision are eligible to participate in this study. Patients will be randomly assigned to one of two treatment groups. One group will receive a 1-mg implant that releases 0.8 micrograms of drug each day; the second group will receive a 2-mg implant that delivers 1.4 micrograms of drug a day.

Before surgery, patients will have a medical history, basic physical examination, and complete eye examination, including special tests called electroretinogram and fluorescein angiography. An electroretinogram measures the electrical responses generated in the retina in the back of the eye. Fluorescein angiography uses a special camera to photograph the retina, showing the condition of the blood vessels in the eye.

The surgical procedure to place the implant takes about 1.5 hours and may be done under either local or general anesthesia. Patients will stay in the hospital overnight. After discharge from the hospital, they will return for follow-up visits 1 and 2 weeks after surgery, then once a month for 6 months, and then every 3 months until the implant is depleted of drug or removed. During these follow-up visits, eye examinations will be repeated to evaluate the effects of the implant on the eye. Repeat blood tests will measure the amount of cyclosporin in the blood and the drug's effect on the kidneys. When the implant runs out of drug (between 2 and 3 years), it may be removed or left in place.


Condition Intervention Phase
Eye Disease
Inflammation
Uveitis
Drug: Cyclosporin A Implant
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Primary Purpose: Treatment
Official Title: A Pilot Study of a Sustained-Release Cyclosporine A Implant for Uveitis

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Estimated Enrollment: 10
Study Start Date: May 1998
Estimated Study Completion Date: March 2004
Detailed Description:

Sight threatening uveitis may require long term use of systemic immunosuppressants. In some patients, aggressive systemic immunosuppressive therapy fails to control inflammation and can lead to serious side effects. Oral Cyclosporin A (CsA) has been shown in several human trials to be effective in treating chronic uveitis. This pilot study will assess the safety, and to some extent efficacy, of a novel intraocular CsA release implant in patients with active inflammation and poor visual acuity in one eye despite immunosuppressant therapy. Patients will be randomly assigned to receive in one eye a 1 or 2 mg CsA implant releasing at either 0.8 microgram per day or 1.4 microgram per day respectively. The main purpose of the study is to assess the safety of the CsA implant. Secondary outcomes will include a change from baseline in the ocular inflammation, visual acuity, and the need for concomitant anti-inflammatory medications.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA:

Age range: 15 or older.

Active non-infectious intermediate, posterior or panuveitis present for at least 6 months despite systemic immunosupressive therapy including at least 20 mg of oral prednisone or use of another immunosuppressive agent.

Visual acuity worse than 20/80 (55 letters) and better than 5/200 (4 letters) in the eye to receive the CsA implant, and better than 20/80 (54 letters) in the non-study eye.

Bilateral or unilateral uveitis with active inflammation in one eye only (eye to be implanted). Patients may continue systemic immunosuppressants with the exception of systemic CsA. Patients may not take greater than 1 drop of topical steroid four times a day in the eye to be implanted for maintenance of anterior segment inflammation after 1 month postoperatively.

Recordable electroretinogram (ERG).

Willingness and the ability, with assistance of a care giver, if necessary, to comply with treatment and follow-up procedures.

The ability to understand and sign an informed consent form which must be obtained prior to treatment.

Negative serum pregnancy test (females of childbearing potential only).

Normal serum creatinine (males 0.9 - 1.4 mg/dL, females 0.7 - 1.3 mg/dL).

No current or past history of retinal detachment.

EXCLUSION CRITERIA:

Current or past history of retinal detachment.

Pregnant or lactating patients or patients with potential for conception unless using effective contraception. Fertile males must use effective contraception. Contraception would no longer be mandatory for participation in this study at three months postoperatively assuming (1) negligible CsA absorption, (2) patient is not taking any other medications that may affect a developing fetus or spermatogenesis.

Patients who received therapy within the previous one week with any nephrotoxic drugs.

Patients having a known allergy to CsA.

Patients receiving current therapy with CsA. Patients need to be off of systemic CsA seven days prior to implant surgery. Patients may continue other immunosuppressive therapies if needed to control inflammation in contralateral (non-study) eye provided the inflammation is currently not active.

  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: NCT00001737

Locations
United States, Maryland
National Eye Institute (NEI)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00001737     History of Changes
Other Study ID Numbers: 980110, 98-EI-0110
Study First Received: November 3, 1999
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Eye
Immunosuppression
Inflammation
Therapy
Vitreous
Uveitis

Additional relevant MeSH terms:
Inflammation
Uveitis
Chorioretinitis
Eye Diseases
Pathologic Processes
Uveal Diseases
Retinitis
Retinal Diseases
Choroiditis
Choroid Diseases
Uveitis, Posterior
Panuveitis
Cyclosporins
Cyclosporine
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on September 18, 2014