Cysteamine Eye Drops to Treat Corneal Crystals in Cystinosis

NCT00001213 | Completed Phase 2 Results

• 2 other identifiers: 86006286-EI-0062
• Study Type: interventional
• Target: 328
• Locations: 1 country
• Sites: 1

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.

Conditions

Cystinosis

Keywords

Cysteamine Eye Drops; Nephropathic Cystinosis; Corneal Crystals; Benzalkonium; Toxicity; Efficacy; Cystinosis

Outcome Measures

Primary Outcomes (2)

• Number of Participants With Serious and Non-Serious Adverse Events

  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.

  Any Time Point up to 27 Years

• Number of Eyes With a Corneal Cystine Crystal Score (CCCS) Response

  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.

  Any Time Point Up to 19 Years

Study Arms (1)

Cysteamine topical solution

EXPERIMENTAL

Cysteamine topical solution administered hourly while awake in both eyes

Drug: Cysteamine

Interventions

Cysteamine DRUG

Cysteamine topical solution

Eligibility Criteria

• Age: 2 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Eye Institute (NEI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (5)

• Kaiser-Kupfer MI, Fujikawa L, Kuwabara T, Jain S, Gahl WA. Removal of corneal crystals by topical cysteamine in nephropathic cystinosis. N Engl J Med. 1987 Mar 26;316(13):775-9. doi: 10.1056/NEJM198703263161304.

  PMID: 3821824 BACKGROUND

• Kaiser-Kupfer MI, Gazzo MA, Datiles MB, Caruso RC, Kuehl EM, Gahl WA. A randomized placebo-controlled trial of cysteamine eye drops in nephropathic cystinosis. Arch Ophthalmol. 1990 May;108(5):689-93. doi: 10.1001/archopht.1990.01070070075038.

  PMID: 2185723 BACKGROUND

• Gahl WA. Cystinosis coming of age. Adv Pediatr. 1986;33:95-126. No abstract available.

  PMID: 3541536 BACKGROUND

• Gahl WA, Kuehl EM, Iwata F, Lindblad A, Kaiser-Kupfer MI. Corneal crystals in nephropathic cystinosis: natural history and treatment with cysteamine eyedrops. Mol Genet Metab. 2000 Sep-Oct;71(1-2):100-20. doi: 10.1006/mgme.2000.3062.

  PMID: 11001803 BACKGROUND

• Iwata F, Kuehl EM, Reed GF, McCain LM, Gahl WA, Kaiser-Kupfer MI. A randomized clinical trial of topical cysteamine disulfide (cystamine) versus free thiol (cysteamine) in the treatment of corneal cystine crystals in cystinosis. Mol Genet Metab. 1998 Aug;64(4):237-42. doi: 10.1006/mgme.1998.2725.

  PMID: 9758713 BACKGROUND

MeSH Terms

Conditions

Cystinosis

Interventions

Cysteamine

Condition Hierarchy (Ancestors)

Lysosomal Storage Diseases; Metabolism, Inborn Errors; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Mercaptoethylamines; Ethylamines; Amines; Organic Chemicals; Sulfhydryl Compounds; Sulfur Compounds

Limitations and Caveats

Due to the progressive nature of the drug's development, this protocol reflects the culmination of cysteamine studies performed at NIH. The combined analyses of the data is presented and not the data or analyses of one individual protocol.

Results Point of Contact

• Title: Rachel J. Bishop, MD, Principal Investigator, National Eye Institute
• Organization: National Institutes of Health

bishopra@nei.nih.gov

301-402-3771

Study Officials

• Rachel J Bishop, M.D.

  National Eye Institute (NEI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: April 1, 1986
• Primary Completion: July 1, 2013
• Study Completion: July 1, 2013
• Last Updated: July 22, 2014
• Results First Posted: July 22, 2014

Record last verified: 2014-06

Locations

US (1)