Funded by The Cystinosis Research Foundation
Funded by The Cystinosis Research
Foundation
Dr. Dohil is ready to begin the
study and patients interested in participating.
Click Here to Read the
Details
Research design and methods: This study will evaluate the
absorption/effect of cysteamine administered into the stomach, jejunum, and
colon.
Six cystinosis patients over the age of 12 will be recruited
nationwide and six adult control subjects who are local will be admitted to
UCSD Clinical Research Center (CRC) for 5 days.
Cystinosis patients
will stop taking cysteamine 48 hours before the study starts. They will need to
stop taking various medications14 days prior to the study.
Numerous lab
tests will be done before and throughout the study.
A naso-enteric
tube, designed for this study will be used. An inflated balloon will aid the
passage of the catheter through the small intestine into the colon.
Some fasting (not including water) will take place. Blood samples will
be collected, gamma camera digital images will be taken, and fluoroscopy will
be used to determine tube position.
Human Subjects: There are
inclusion and exclusion criteria, many consent and risk issues. The potential
benefits are that the study may cause improved understanding of how cysteamine
is absorbed from the intestine and how it causes symptoms. The data may help in
future development of safe and effective controlled-release preparation of
cysteamine which would improve quality of life for all those affected by
cystinosis.
Background: Cysteamine causes ulcers. It has been
used to cause ulcers in laboratory animals. It is good for reducing the rate of
renal failure in those with cystinosis, but it is hard on their stomachs. It
increases gastric acid production. This causes problems. Patients are sometimes
unable to take cysteamine at all, and others cannot take a full dose. Also a
twice daily dose of cysteamine would be less life disrupting than the six hour
doses. More information about cysteamine absorption is needed in order to
consider better delivery systems. Therefore they need to learn more about where
cysteamine is absorbed and whether a change or delivery or dosage would be
beneficial. They will use patients over 12 initially, but plan on using younger
patients later.
Preliminary studies: In 1976 they gave cysteamine
intravenously. Twenty-four hours after the dose was given, leukocyte cystine
level was almost as low as it was one hour after the drug was first
administered. It was very comparable to the dose patients are now taking every
six hours orally.
They have discovered that even though a patient had
appropriate leukocyte cystine levels, there were large numbers of cystine
crystal deposited within the lysosomes of the stomach lining. This may indicate
that patients are being under-treated. "In other words, the leukocyte cystine
level may not reflect the cystine level of some other tissues."
If
cysteamine is better absorbed in other intestinal sites (perhaps due to pH
levels), more cysteamine may get into the lysosomes. If more cysteamine gets
into the lysosomes, it might remain in the cell for a longer period of time. If
this is true, a it is possible to produce a capsule of cysteamine that is
released at the optimal site within the intestine allowing less frequent
dosing.
Dr. Jerry Schneider (UCSD) has talked with Mylan Pharmaceuticals
and they are very receptive to changing Cystagon if there was evidence that it
would help patients with cystinosis. Dr. Schneider will remain in contact with
John Kirsch, Assistant Director of Product Development and Andrew Shaw a
pharmacokinetic expert, both at Mylan.
Dr. Dohil is ready to begin the
study and patients interested in participating.
Click Here to Read the
Details