This study will continue to evaluate the long term safety and effectiveness of cysteamine eye drops for treating cystine crystals in the corneas of patients with cystinosis. These drops are not sold commercially and are available only through this study. New patients may enroll in the study to obtain them.

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, perhaps because it does not reach the corneal cells. The current study was begun 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.

New patients in this study will undergo an eye examination that includes tests of retinal function and evaluation of visual acuity, night vision and color vision, age permitting. They will take cysteamine eye drops in both eyes every hour during waking hours. For the first week of treatment, patients will be followed daily for possible side effects. Thereafter, eye examinations will be done every 12 months, and photographs will be taken of the eyes to assess the effects of treatment.

Condition	Treatment or Intervention	Phase
Cystinosis	Drug: Cysteamine	Phase II

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. For example, kidney failure generally occurs by 10 years of age and there is abundant crystal accumulation in the cornea by two years of age. Over the past 15 years, cystinotic children have been treated with oral cysteamine under NICHD protocol #78-CH-0093 and FDA IND #11065. Cysteamine therapy improved growth and stabilized renal function in pre-renal transplant cystinotics, without substantial toxicity. There was no noticeable effect on cystine crystal accumulation in the cornea, most likely because of inadequate local cysteamine concentration in the cornea.

Therefore, after animal studies demonstrating safety, a double masked clinical trial was begun in 1986 to test the efficacy of 0.1% topical cysteamine which proved safe and effective in removing corneal crystals in four young patients. The clinical trial was amended in 1988 to allow for an increase of the concentration to 0.5%. Because of the desirability to demonstrate a reduction of the crystals in older patients, and to determine if the frequency of administration could be reduced, the clinical trial was amended in 1988 to allow for an increase of the concentration to 0.5%. This resulted in a successful clinical trial. In age group I (less than three years of age), there have been 30 randomized patients, 15 with successful code breaking and in age group II, (greater than 3 years of age), there have been 69 randomized patients with successful code breaking in 20.

In dealing with the FDA in negotiations to have this preparation become marketable for new drug approval (NDA), it became apparent that the cysteamine eyedrops would need to be prepared with a preservative. Consequently, protocol 92-EI-0203 was begun to compare the safety and equivalency of cysteamine + benzalkonium (preservative) with that of cysteamine alone. There was no evidence of toxicity attributable to the benzalkonium. However, in 1993, a directive from the FDA required that we cease protocol 92-EI-0203 and that all patients in 86-EI-0062 be converted to cysteamine + benzalkonium in both eyes. All new patients were admitted to this study and the patient's clinical course compared to the natural history of the disease as a control.

In August of 1994 , we initiated a protocol for new patients testing the safety and efficacy of cystamine (the disulfide of cysteamine) with that of cysteamine itself. While side effects were negligible to both preparations, cysteamine was more beneficial in removing corneal crystals than was cystamine. Therefore, that protocol is being discontinued, and both current and past patients need to be placed back on protocol 86-EI-0062.

We propose to continue 86-EI-0062 to provide eyedrops to needy patients and to determine if long term 0.5% topical cysteamine is effective in maintaining a crystal free or near crystal free cornea. The patients will be examined every 12 months for considerations of safety and efficacy which will be gauged by regression or lack of preogression of corneal crystal formation

Genders Eligible for Study:  Both

Criteria

INCLUSION CRITERIA:
Cystinosis patients diagnosed by elevated leukocyte cystine values on the presence of corneal crystals will be invited to participate in this protocol. Cystinosis will be diagnosed by elevated leukocyte or fibroblast cystine content. In particular, young patients whose corneas have not yet been fully packed with crystals, and older patients having frequent corneal erosions will be invited to participate.

Maryland
      National Eye Institute (NEI), 9000 Rockville Pike,  Bethesda,  Maryland,  20892,  United States; Recruiting

Study ID Numbers:  860062; 86-EI-0062
Record last reviewed:  May 5, 2004
Last Updated:  May 5, 2004
Record first received:  November 3, 1999
ClinicalTrials.gov Identifier:  NCT00001213
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2004-11-18