P-glycoprotein Inhibition as Adjunct Treatment for Medically Refractory Epilepsy.
Status:
Terminated
Trial end date:
2010-10-01
Target enrollment:
Participant gender:
Summary
In up to 1 out of 3 patients with epilepsy, seizures continue to occur despite the use of one
or more antiepileptic medications. Patients also have significant problems with side-effects
of these medications as doses are increased.
Our body naturally generates miniature pumps located on the surfaces of many organs to get
rid of toxic substances, and antiepileptic medications can be considered by the cells of the
body to be a toxin. Research with epileptic brain regions have shown an increase in the
amount of drug pumps, therefore getting rid of antiepileptic drugs. One of these pumps is
called p-glycoprotein (P-gp for short). Medications may be unable to penetrate and stay
within the parts of the brain that need them them most. This may mean that the amount of drug
is actually lower in the parts of the brain that cause seizures, and higher in the rest of
the brain, which may be why patients may still feel side-effects when seizures are still
occurring.
Research in animals has shown that blocking the P-gp pumps can improve how bad, and how many
seizures occur as well as the length of seizures. Blockage of the pumps can be done using a
different type of medication. Some medications that are used for common problems have been
discovered to also block P-gp pumps. One of these, carvedilol, is used to treat heart failure
and high blood pressure. It has been found to be very safe in these patients, and does not
have a lot of side-effects. We plan to add this medication in addition to patient's
anti-seizure medications to see if it will improve epileptic seizures.
The reason why some patients have high amounts of P-gp pumps and others do not may be related
to their genetics. A simple blood test can be used to determine a person's potential to
produce high quantities of the pumps. This study will also attempt to show that the genetics
will affect how well the P-gp blocking will work.
Phase:
Phase 2/Phase 3
Details
Lead Sponsor:
Columbia University
Collaborators:
American Epilepsy Society GlaxoSmithKline Milken Family Foundation