Clinical Trial: Cysteamine Eye Drops to Treat Corneal Crystals in Cystinosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Trial of Topical Cysteamine in the Treatment of Corneal Cystine Crystal Accumulation in Cystinosis

Brief Summary:

Cystinosis is an inherited disease that results in poor growth and kidney disease, among other things. The damage to the kidneys and other organs is thought to be due to accumulation of cystine inside the cells of various body tissues. This chemical also accumulates in the cornea-the covering of the eye over the pupil and iris. After 10 to 20 years, the corneas of some patients become so packed with crystals that the surfaces may become irregular, occasionally causing small, painful breaks.

Patients enrolled in a NIH study on cystinosis are receiving the drug cysteamine. Taken by mouth, this drug reduces cystine in some tissues, but not in the cornea. This study began in 1986 to test whether cysteamine eye drops could prevent or reduce corneal cystine crystals in these patients. The drops have been very effective in removing crystals and reducing pain in patients who take the medication as directed. Patients who do not take the medication as prescribed do not benefit.

After the effectiveness of the drops was proven, the main purpose was modified to continue to evaluate the long-term safety and effectiveness of cysteamine eye drops for treating cystine crystals in the corneas of patients with cystinosis until the drops are approved by the Food and Drug Administration (FDA). When the New Drug Application (NDA) for the Sigma-Tau standard formulation is granted, this protocol will be terminated.

Detailed Summary:

Protocol 86-EI-0062 began as a randomized, double-masked, placebo controlled study to evaluate the efficacy and safety of 0.5% topical cysteamine but was subsequently amended as a natural history protocol. Additional protocols conducted at the National Eye Institute (NEI) at the National Institutes of Health (NIH) began after this protocol and tested various formulations of cysteamine topical solution for efficacy and safety in patients with cystinosis. Subjects from these NIH protocols testing various formulations were ultimately transferred to this natural history protocol for open-label treatment once it was established that the formulation within this study was the most effective. All subjects enrolled in this protocol received the most effective cysteamine topical solution formulation in both eyes. The control was defined as the natural course of corneal crystal accumulation in patients with cystinosis. The efficacy data were obtained from all of the studies conducted at NIH evaluating various cysteamine ophthalmic solution formulations from 1986 until 2005. The safety data were collected from 1986 until the termination of this protocol in July 2013.

OBJECTIVE:

The free thiol cysteamine depletes cystinotic leukocytes and other cells of cystine, whose accumulation is considered the cause of organ damage in cystinosis. This organ damage involves most tissues of the body. Cysteamine therapy improved growth and stabilized renal function in pre-renal transplant cystinosis, without substantial toxicity but there was no noticeable effect on cystine crystal accumulation in the cornea, most likely because of inadequate local cysteamine concentration in the cornea. Previous studies have shown the safety of cysteamine 0.5% topical solution in benzalkonium chloride and its efficacy in resolving the cystine corneal crystals. The m
Sponsor: National Eye Institute (NEI)

Current Primary Outcome:

• Number of Participants With Serious and Non-Serious Adverse Events [ Time Frame: Any Time Point up to 27 Years ]
  Since efficacy of ophthalmic cysteamine was established and a New Drug Application (NDA) filed, the post-hoc primary outcome measure is the evaluation of safety information. There was no specified time frame for this outcome measure, as safety data was being collected until the drug became available for commercial purchase in May 2013.
• Number of Eyes With a Corneal Cystine Crystal Score (CCCS) Response [ Time Frame: Any Time Point Up to 19 Years ]

  Response is defined as a decrease from baseline of at least 1 in Corneal Cystine Crystal Score (CCCS) at any time on study when baseline CCCS is greater than or equal to 1, or CCCS does not increase at least 1 at any time on study when baseline CCCS is less than 1.

  The CCCS is based on a library of slit-lamp photographs of corneas with increasing crystal densities (0-3). Slit-lamp photos were to be taken to assess the extent of the corneal crystal accumulation. To minimize bias when assessing the extent of corneal crystal accumulation, photos were centrally graded at the National Eye Institute (NEI) where each photo was graded independently by masked graders. If more than one CCCS was recorded in a given study year, the highest (worst) CCCS value was used for that year.

  The results were obtained from a combined analyses of the NIH cysteamine studies evaluating various cysteamine ophthalmic solution formulations from 1986 through 2005.

Original Primary Outcome:

Current Secondary Outcome:

Original Secondary Outcome:

Information By: National Institutes of Health Clinical Center (CC)

Dates:
Date Received: November 3, 1999
Date Started: April 1986
Date Completion:
Last Updated: June 20, 2014
Last Verified: June 2014