Prospective Study of Rapamycin for the Treatment of SLE
| Status: | Recruiting |
|---|---|
| Conditions: | Lupus |
| Therapuetic Areas: | Immunology / Infectious Diseases |
| Healthy: | No |
| Age Range: | 18 - Any |
| Updated: | 2/7/2015 |
| Start Date: | October 2008 |
Systemic lupus erythematosus (SLE) is an autoimmune disease of unknown origin. It involves
multiple organs including the joints, skin, kidneys and central nervous system. The disease
process is caused by a dysfunction of the immune system. The drugs currently used for the
treatment of SLE are only partially effective and carry significant risks for side-effects.
Rapamycin, also called sirolimus or Rapamune, has been approved by the FDA to prevent
rejection of organ transplants at daily doses of 2 mg to 8 mg. Patients that were resistant
or intolerant to conventional medication have been effectively treated with Rapamycin and
were able to decrease the amount of prednisone they needed.
The purpose of this study is to prospectively determine the therapeutic efficacy and
mechanism of action of Rapamune in patients with SLE. Healthy subjects not receiving
Rapamune will be asked to donate blood to serve as controls.
As part of the research effort to understand the reason for the variations in the effects of
treatment drugs by different individuals, a sub-study of the DNA makeup of subjects enrolled
in the trial will also be done. The purpose of the sub-study is to possibly determine
whether different responses to the drugs used to treat SLE have a correlation with the
differences in the genetic makeup of the subjects.
multiple organs including the joints, skin, kidneys and central nervous system. The disease
process is caused by a dysfunction of the immune system. The drugs currently used for the
treatment of SLE are only partially effective and carry significant risks for side-effects.
Rapamycin, also called sirolimus or Rapamune, has been approved by the FDA to prevent
rejection of organ transplants at daily doses of 2 mg to 8 mg. Patients that were resistant
or intolerant to conventional medication have been effectively treated with Rapamycin and
were able to decrease the amount of prednisone they needed.
The purpose of this study is to prospectively determine the therapeutic efficacy and
mechanism of action of Rapamune in patients with SLE. Healthy subjects not receiving
Rapamune will be asked to donate blood to serve as controls.
As part of the research effort to understand the reason for the variations in the effects of
treatment drugs by different individuals, a sub-study of the DNA makeup of subjects enrolled
in the trial will also be done. The purpose of the sub-study is to possibly determine
whether different responses to the drugs used to treat SLE have a correlation with the
differences in the genetic makeup of the subjects.
40 SLE subjects and 40 healthy controls are being recruited. The study will lasts 1 year
with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood
once.
The study drug, Rapamune, is manufactured by Pfizer Pharmaceuticals. It is taken by mouth at
a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of
6-15 ng/ml (the levels found to be effective for preventing organ rejections).
Blood samples are obtained before taking Rapamune, every two weeks for the first month, then
every three months until 1 year, and then three months later to check the effect of
discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20
teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and
the remaining 3 visits every 3 months.
Routine laboratory work will be performed. Part of the blood drawn will be used for research
and part will be used for routine lab work as part of standard of care.
The non-routine laboratory studies include:
1. Assessment of mitochondrial function in intact T cells
2. Analysis of mTOR activity, FKBP12 expression, and global gene expression in lupus T
cells.
3. Predictors of therapeutic efficacy of rapamycin in SLE.
The study drug levels will be checked at every visit. The non-routine laboratory studies
will be performed at Visits 0 and 8 for SLE subjects and at Visit 0 for the healthy control
subjects.
Healthy control subjects will be matched by age ( a decade or less), gender, and ethnic
origin. They will be recruited and analyzed on the same day as lupus subjects.
All subjects will sign an informed consent at visit 0. There is a separate informed consent
for the main study, one for the SLE subjects and one for the Healthy Controls. The same
subjects can participate in the genetic sub-study. They must sign another informed consent
for the genetic sub-study, one for the SLE subjects and one for the Healthy Controls. There
is no need for additional blood drawing since part of the blood drawn for the main study can
be used for the genetic sub-study.
with 9 study visits from day 0 to day 360. The healthy controls only need to donate blood
once.
The study drug, Rapamune, is manufactured by Pfizer Pharmaceuticals. It is taken by mouth at
a starting dose of 2mg/day. The dose is adjusted to achieve blood levels in the range of
6-15 ng/ml (the levels found to be effective for preventing organ rejections).
Blood samples are obtained before taking Rapamune, every two weeks for the first month, then
every three months until 1 year, and then three months later to check the effect of
discontinuing rapamycin. Each SLE subject will be asked to provide up to 100 ml (20
teaspoons) of blood at each visit. The first 6 visits will take place within 3 months and
the remaining 3 visits every 3 months.
Routine laboratory work will be performed. Part of the blood drawn will be used for research
and part will be used for routine lab work as part of standard of care.
The non-routine laboratory studies include:
1. Assessment of mitochondrial function in intact T cells
2. Analysis of mTOR activity, FKBP12 expression, and global gene expression in lupus T
cells.
3. Predictors of therapeutic efficacy of rapamycin in SLE.
The study drug levels will be checked at every visit. The non-routine laboratory studies
will be performed at Visits 0 and 8 for SLE subjects and at Visit 0 for the healthy control
subjects.
Healthy control subjects will be matched by age ( a decade or less), gender, and ethnic
origin. They will be recruited and analyzed on the same day as lupus subjects.
All subjects will sign an informed consent at visit 0. There is a separate informed consent
for the main study, one for the SLE subjects and one for the Healthy Controls. The same
subjects can participate in the genetic sub-study. They must sign another informed consent
for the genetic sub-study, one for the SLE subjects and one for the Healthy Controls. There
is no need for additional blood drawing since part of the blood drawn for the main study can
be used for the genetic sub-study.
Inclusion Criteria:
For SLE Subjects:
- SLE patients who exhibit ongoing disease activity by SLEDAI greater or equal to 4.
- SLE patients whose disease activity is controlled by administration of
corticosteroids, most commonly, at least 10 mg/day of prednisone.
- 18 years of age or older.
- Updated vaccinations prior to study entry.
- Use of effective contraception for male patients before, during and up to 12 weeks
after sirolimus therapy.
For Healthy Control Subjects:
- 18 years of age or older
- Must be matched with one of the SLE patients enrolled in the study by age, gender and
ethnic origin
- Must not have any acute or chronic illness.
Exclusion Criteria:
For SLE Subjects:
- Patients who are pregnant.
- Patients with allergy or intolerance to sirolimus.
- Patients with life-threatening manifestations of SLE.
- Patients with proteinuria exceeding 500 mg/24 h or urine protein/creatine ratio >0.5.
- Patients with total cholesterol > 300 mg/dl or triglyceride > 400 mg.dl will be
excluded.
- Patients with acute infection requiring antibiotics.
- Patients on sirolimus who develop infections and require intravenous antibiotics and
fail to show clinical improvement in 5 days.
- Patients concurrently undergoing B cell-depleting therapy, cyclophosphamide,
cyclosporine, and tacrolimus.
- Patients who have received investigational biologic B-cell depleting products within
one year of study initiation.
- Patients with a history of chronic viral infections (e.g., HIV, hepatitis B,
hepatitis C) or with a history of a malignancy (except non-melanoma skin cancer).
- Due to interference with sirolimus metabolism, subjects will not be allowed to
receive concomitant rifampin, ketoconazole,voriconazole, itraconazole, erythromycin,
or clarithromycin during the study.
- Patients with any type of interstitial lung disease.
For Healthy control Subjects:
- Subjects who are pregnant.
- Subjects with any acute or chronic illness.
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