The Treatment of Uveitic Cystoid Macular Edema With Topical Interferon Gamma

Condition(s) targeted: Uveitis

Intervention: Interferon Gamma 1-b (Drug)

Phase: Phase 1

Status: Recruiting

Sponsored by: National Eye Institute (NEI)

Overall contact:
Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

Background:

- Uveitis is a serious inflammatory condition that affects the eye and can cause vision

loss. A common secondary problem associated with uveitis is macular edema (swelling). The macula is the part of the eye that is important for central vision, and swelling of the macula can lead to further vision loss. This condition is usually treated by medicines that target the immune system, but these medicines sometimes do not work or may cause side effects.

- Interferon gamma-1b (Actimmune(Registered Trademark)) is a bioengineered protein that

can alter the way inflammatory cells work in the immune system. Interferon gamma-1b is given as an intramuscular injection; however, this study will use the drug as an eye drop. This study represents the first time that interferon gamma-1b is given as an eye drop. Researchers hope that interferon gamma-1b will treat macular edema by decreasing the swelling in the back of the eye.

Objectives:

- To investigate the safety and effectiveness of treating uveitis-associated macular edema

with interferon gamma-1b.

Eligibility:

- Individuals 18 years of age and older who have been diagnosed with macular edema

associated with uveitis (in one or both eyes) for at least 3 months.

Design:

- Participants will have three planned clinic visits during this study over the course of

2 weeks.

- All participants will have a medical history and eye examination.

- When receiving the drops, participants will have optical coherence tomography (a

detailed scan of the retina) 60 minutes and 30 minutes before the drops; upon receiving the drops; and 30, 60, and 120 minutes after receiving the drops.

- After receiving the drops, participants will have another eye examination, blood drawn

for samples, and further scans.

- Participants will be asked to return to the NIH Clinical Center 1 week after receiving

the drops for an evaluation....

Official title: The Treatment of Uveitic Cystoid Macular Edema With Topical Interferon Gamma

Study design: Treatment, Non-Randomized, Open Label, Uncontrolled, Single Group Assignment, Safety/Efficacy Study

Primary outcome: The primary outcome is the change in central macular thickness as measured by OCT as compared with baseline.

Secondary outcome: Secondary outcomes include: changes in macular volume as measured by OCT, changes in visual acuity, changes in intraocular pressure and changes in intraocular inflammation.

Detailed description: Objective: Information gathered from our laboratories suggests that cystoid macular edema (CME) is caused by the disequilibrium of the Jak/Stat and mTor signal transduction pathways in the retinal pigment epithelium (RPE). We wish to test this hypothesis by stimulating the Jak/Stat pathway with topically applied interferon gamma-1b.

Study Population: Five participants with CME secondary to uveitis will receive a topical ocular instillation of interferon gamma-1b.

Design: This Phase I, non-randomized, prospective, uncontrolled, dose-escalation, single-center study will involve a one-time instillation or series of instillations of interferon gamma-1b on the cornea and measure the potential response with optical coherence tomography (OCT) over a three-hour period. Treatment success is defined as a 25% decrease in macular thickness at any timepoint post-instillation as compared to baseline. The first two participants will receive one instillation (each instillation contains 10 microg in 0. 05 mL solution), the next two participants will receive two instillations and the final

participant will receive three instillations. OCT will be obtained at - 60 minutes, -30

minutes and just before the instillation(s). Repeat OCTs will be taken at +30 minutes, +60 minutes and +120 minutes. All participants will return for a one-week safety visit.

Outcome Measures: The primary outcome is the change in central macular thickness as measured by OCT in response to interferon gamma-1b as compared with baseline. Secondary outcomes include changes in macular volume as measured by OCT, visual acuity, intraocular pressure, intraocular inflammation and ocular surface irritation assessed by fluorescein staining of the cornea and conjunctiva to assess toxicity.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

- INCLUSION CRITERIA:

1. Participant must be 18 years of age or older.

2. Participant must understand and sign the protocol's informed consent document.

3. Participant has a diagnosis of intermediate, panuveitis or posterior uveitis of at least three months prior to study enrollment and has associated CME secondary to uveitis in at least one eye (the study eye).

4. Participant has a central macular thickness greater than or equal to 250 microns in the study eye.

5. Participant is willing to comply with the study procedures and is expected to be able to return for all study visits.

6. Participant has visual acuity of 20/200 or better in the study eye.

7. Female participants of childbearing potential must not be pregnant or breast-feeding and must have a negative urine pregnancy test within 24 hours before study medication administration.

8. Both female participants of childbearing potential and male participants able to father a child must agree to practice an adequate birth control during the study and for six weeks following the administration of study medication. Acceptable methods of birth control include hormonal contraception (birth control pills, injected hormones or vaginal ring), intrauterine device, barrier methods with spermicide (diaphragm with spermicide, condom and spermicide) or surgical sterilization (hysterectomy, tubal ligation or vasectomy).

EXCLUSION CRITERIA:

1. Participant is expected to be unable to tolerate the ocular instillation.

2. Participant is unable to undergo OCT testing.

3. Participant had herpes keratitis in the past.

4. Participant is diagnosed with multiple sclerosis.

5. Participant has a significant active infection (an infection requiring treatment as determined by the medical team) or a history of chronic or recurrent infections that in the PI's best medical judgment would preclude participation.

Patient Recruitment and Public Liaison Office, Phone: (800) 411-1222, Email: prpl@mail.cc.nih.gov

National Institutes of Health Clinical Center, 9000 Rockville Pike, Bethesda, Maryland 20892, United States; Recruiting

NIH Clinical Center Detailed Web Page

Related publications:

Andrews HE, Nichols PP, Bates D, Turnbull DM. Mitochondrial dysfunction plays a key role in progressive axonal loss in Multiple Sclerosis. Med Hypotheses. 2005;64(4):669-77.

Artuch R, Aracil A, Mas A, Colome C, Rissech M, Monros E, Pineda M. Friedreich's ataxia: idebenone treatment in early stage patients. Neuropediatrics. 2002 Aug;33(4):190-3.

Artuch R, Aracil A, Mas A, Monrós E, Vilaseca MA, Pineda M. Cerebrospinal fluid concentrations of idebenone in Friedreich ataxia patients. Neuropediatrics. 2004 Apr;35(2):95-8.

Starting date: July 2009
Ending date: December 2009
Last updated: September 19, 2009