This study will evaluate the safety, tolerability, and effect of the drug Rolipram on
multiple sclerosis (MS). It will examine whether Rolipram can dampen the part of the immune
response believed to lead to MS and reduce disease activity.
Patient with multiple sclerosis who are between the ages of 18 and 65 may be eligible for
this study. Candidates will be screened with a complete neurological and medical evaluation.
Participants will complete three study phases-baseline, treatment and follow-up, as follows:
Baseline (3 months) - Approximately four magnetic resonance imaging (MRI) scans will be
obtained to assess MS activity. Participants with MS activity above a certain level will
continue with the treatment phase.
Treatment (8 months) - Patients will take Rolipram tablets in increasing doses every 2 to 3
days for the first month of this phase until their individual maximum tolerated dose is
established. Dosing will continue at that level for the rest of the treatment phase. Dosing
is in the morning, midday and evening. Patients will be seen monthly in the clinic for
examination and MRI scans.
Follow-up - Participants will have monthly exams and MRIs for 3 months following the
treatment phase, after which their participation in the study ends.
Patients' monthly visits during treatment and follow-up include a neurological examination to
assess disease status; MRI to assess brain changes; and blood and urine collection to monitor
liver, kidney and other functions. In addition, a lumbar puncture (spinal tap) is done during
the last month of the baseline phase and one month after treatment ends to study changes in
the spinal fluid surrounding the brain and spinal cord, and leukapheresis is done once during
the last month of the baseline phase and once during the last month of treatment to collect
white blood cells for study. These procedures involve the following:
MRI uses a strong magnetic field and radio waves instead of X-rays to produce images showing
structural and chemical changes in tissues. The patient lies on a table in a narrow cylinder
(the scanner) containing a magnetic field and images are taken. A contrast agent called
gadolinium is injected into a vein during the last set of images to help identify new
lesions. Magnetic resonance spectroscopy, which is similar to MRI, is also done once during
the baseline phase, at 4 months and at 8 months to measure brain chemicals. For the spinal
tap, a local anesthetic is given and a needle is inserted in the space between the bones
(vertebrae) in the lower back. About 2 tablespoons of fluid is collected through the needle.
For leukapheresis, whole blood is collected through a needle placed in an arm vein. The blood
circulates through a machine that separates it into its components. The white cells are
removed and the red cells, platelets and plasma are returned to the body through a second
needle placed in the other arm.
Patients may also have studies to measure levels of Rolipram in the blood. These are done on
study days 1 and 29 and at months 2, 4, and 6. For days 1 and 29, a catheter is placed in an
arm vein and 4 ml. of blood is drawn immediately before the morning dose and at several
intervals from 20 minutes to 6 hours after the dose. For the other tests, a single 4-ml
sample is collected before the noon dose.
Phase:
Phase 2
Details
Lead Sponsor:
National Institute of Neurological Disorders and Stroke (NINDS)