Clinical trial NCT00304954
Conditions: Age-Related Macular Degeneration Choroidal Neovascularization
Keywords: Age-Related Macular Degeneration Rapamycin Remicade Daclizumab Immunosuppression Infliximab Choroidal Neovascularization Sirolimus AMD Ocular Inflammation
Sponsor: National Eye Institute (NEI)
Start date: 2006-02-01; Completion date: 2010-01-01
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study examined whether the anti-inflammatory medicines infliximab, sirolimus or daclizumab, when given with a participant's current therapies, would prevent the growth of new blood vessels in the eye in participants with age-related macular degeneration (AMD).

Participants 55 years of age and older with AMD and drusen larger than 63um may be eligible for this study. Vision in the study eye was between 20/20 and 20/400.

Participants were randomly assigned to one of three treatments - infliximab, sirolimus, or daclizumab - or to observation only. In addition, participants may have been treated by their ophthalmologist as needed for their AMD.

Infliximab and daclizumab were given intravenously (through a vein); infusions were given at enrollment in the study, then at 2 weeks, and then monthly.

Sirolimus was a pill that was taken every other day for the duration of the study. At 6 months, participants were evaluated to see whether continuing treatment would be beneficial.

In addition to treatment or observation, participants underwent the following procedures:

Physical examination at enrollment and 6 months.

Photographs of the back of the eye, fluorescein angiography, indocyanine green angiography and measurement of retinal thickness at enrollment and months 1, 3 and 6.

* Fluorescein angiography evaluated the eye's blood vessels. A yellow dye was injected into an arm vein and traveled to the blood vessels in the eyes. Pictures of the retina were taken using a camera that flashed a blue light into the eye. The pictures show if any dye has leaked from the vessels into the retina, indicating possible blood vessel abnormality.
* Indocyanine green angiography identified feeder vessels that may have supplied abnormal blood vessels. This procedure is similar to fluorescein angiography, but uses a green dye and flashes an invisible light.
* Optical coherence tomography measures retinal thickness. This test shines a light into the eye and produces cross-sectional pictures of the retina. These measurements are repeated during the study to determine whether retinal thickening is getting better or worse, or staying the same.

Tuberculin skin test and chest x-ray at enrollment and 6 months.

Blood tests at enrollment and months 1, 3 and 6.

Detailed description:
There has been much interest in the possible role of the immune system in AMD. Experimental models and patient material have, to date, suggested a role for macrophages and complement. This study hypothesized that the underlying mechanism that leads to choroidal neovascularization (CNV) is similar to those at play in atherosclerosis. If this is the case, the investigators believed that CNV treatment should be amenable to new immunomodulatory agents directed against specific parts of the immune system.

After therapy with anti-angiogenic agents not leading to a persistent remission of CNV due to AMD, participants were treated with one of three immunomodulatory agents or were observed in conjunction with their continued anti-angiogenic therapy. Thus the participant continued with the anti-angiogenic therapy they received after randomization. The investigators hypothesized that this combination therapy would inhibit progression of CNV associated with AMD.

This was an open-label, phase II, randomized, single center clinical trial of 18 study participants randomized to receive one of three immunomodulatory agents or was observed in conjunction with their anti-angiogenic therapy.

Arms: arm 1: Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. arm 2: Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. arm 3: Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months. arm 4: Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography.
Interventions: intervention 1: Intravenous Daclizumab intervention 2: Intravenous Infliximab intervention 3: Observation intervention 4: Oral Rapamycin
Intervention descriptions: intervention 1: Participants randomly assigned to intravenous (IV) daclizumab received 8 mg/kg of IV daclizumab at baseline, then 4 mg/kg of IV daclizumab at Week 2 and then 2 mg/kg of IV daclizumab monthly for the rest of the 6-month study. intervention 2: Participants randomized to IV infliximab received 3 mg/kg of IV infliximab monthly for 6 months. intervention 3: Participants randomly assigned to the observation group were given injections of either bevacizumab (1.25 mg/0.05 mL or 2.5 mg/0.1 mL) or ranibizumab (0.5 mg) if they presented with recurrence of intraretinal or subretinal fluid as seen on Stratus Optical Coherence Tomography. intervention 4: Participants randomly assigned to rapamycin received 2 mg in capsule form every other day for 6 months.

Protocol documents: