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Trial record 17 of 32 for:    CYSTEAMINE

Cysteamine Eye Drops to Treat Corneal Crystals in Cystinosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00001213
Recruitment Status : Completed
First Posted : November 4, 1999
Results First Posted : July 22, 2014
Last Update Posted : July 22, 2014
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) )

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.

Condition or disease Intervention/treatment Phase
Cystinosis Drug: Cysteamine Phase 2

Detailed Description:

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.


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 main purpose of this protocol is to maintain topical cysteamine treatment in patients with nephropathic cystinosis until the drops are approved by the FDA. When the NDA for the Sigma-Tau standard formulation is granted, the present protocol (86-EI-0062) will be terminated.


Up to 350 adults and children over two years old, who have a confirmed diagnosis of cystinosis will be enrolled.


This is an open label treatment protocol. Eligible subjects will receive drops of cysteamine 0.5% topical solution in benzalkonium chloride hourly while awake in both eyes. They will undergo an eye examination at their baseline visit. They will take cysteamine eye drops in both eyes every hour during waking hours. They will return to the NIH Clinical Center for a follow-up safety eye examination one year after the baseline visit, and then every two years thereafter until the drug is available commercially.


The initial pre-specified primary outcome measure was the reduction of cystine corneal crystals. The post-hoc primary outcome measure (after the protocol was modified) was the collection of safety data.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 328 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Topical Cysteamine in the Treatment of Corneal Cystine Crystal Accumulation in Cystinosis
Study Start Date : April 1986
Actual Primary Completion Date : July 2013
Actual Study Completion Date : July 2013

Arm Intervention/treatment
Experimental: Cysteamine topical solution
Cysteamine topical solution administered hourly while awake in both eyes
Drug: Cysteamine

Primary Outcome Measures :
  1. 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.

  2. 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.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No


  • Patients must have a documented clinical diagnosis of cystinosis.
  • Patients should be 2 years old or older.


  • Inability to travel to NIH for a baseline examination, after 1 year, and every two years thereafter for follow-up
  • Inability to cooperate for slit-lamp examination

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00001213

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Eye Institute (NEI)
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Principal Investigator: Rachel J Bishop, M.D. National Eye Institute (NEI)

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Responsible Party: National Eye Institute (NEI) Identifier: NCT00001213     History of Changes
Other Study ID Numbers: 860062
First Posted: November 4, 1999    Key Record Dates
Results First Posted: July 22, 2014
Last Update Posted: July 22, 2014
Last Verified: June 2014
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Eye Institute (NEI) ):
Cysteamine Eye Drops
Nephropathic Cystinosis
Corneal Crystals
Additional relevant MeSH terms:
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Lysosomal Storage Diseases
Metabolism, Inborn Errors
Genetic Diseases, Inborn
Metabolic Diseases
Ophthalmic Solutions
Pharmaceutical Solutions
Central Nervous System Stimulants
Physiological Effects of Drugs
Autonomic Agents
Peripheral Nervous System Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Adrenergic Agents
Adrenergic Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Dopamine Uptake Inhibitors
Cystine Depleting Agents