Prospective Study of Rapamycin for the Treatment of SLE

NCT00779194

Last updated date
Study Location
SUNY Upstate Medical University
Syracuse, New York, 13210, United States
Contact
1-800-718-1021

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Eligibility Criteria
condition
The disease, disorder, syndrome, illness, or injury that is being studied.
Systemic Lupus Erythematosus (SLE)
Sex
Females and Males
Age
Pediatric Trials: 0-17 Years
Adult Trials: 18+ Years
18 + years
Inclusion Criteria
The factors, or reasons, that allow a person to participate in a clinical study.
Show details

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
The factors, or reasons, that prevent a person from participating in a clinical study.
Show details


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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Systemic Lupus Erythematosus (SLE)Prospective Study of Rapamycin for the Treatment of SLE
NCT00779194
  1. Syracuse, New York
ALL GENDERS
18 Years+
years
MULTIPLE SITES
Advanced Information
Descriptive Information
Brief Title  ICMJE Prospective Study of Rapamycin for the Treatment of SLE
Official Title  ICMJE Prospective Study of Rapamycin for the Treatment of SLE
Brief Summary

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.

Detailed Description

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus (SLE)
Intervention  ICMJE Drug: Rapamycin
Rapamycin, is given to this group at a starting dose of 2 mg/day.
Other Name: Rapamune, Sirolimus.
Study Arms  ICMJE
  • Experimental: 1
    SLE subjects receiving the study drug, Rapamune.
    Intervention: Drug: Rapamycin
  • No Intervention: 2
    Healthy control group donating blood for the main study.
  • No Intervention: 3
    SLE subjects donating blood for Genetic sub-study
  • No Intervention: 4
    Healthy control subjects donating blood for the Genetic sub-study
Publications * Lai ZW, Kelly R, Winans T, Marchena I, Shadakshari A, Yu J, Dawood M, Garcia R, Tily H, Francis L, Faraone SV, Phillips PE, Perl A. Sirolimus in patients with clinically active systemic lupus erythematosus resistant to, or intolerant of, conventional medications: a single-arm, open-label, phase 1/2 trial. Lancet. 2018 Mar 24;391(10126):1186-1196. doi: 10.1016/S0140-6736(18)30485-9. Epub 2018 Mar 15.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 12, 2016)
40
Original Estimated Enrollment  ICMJE
 (submitted: October 23, 2008)
80
Study Completion Date  ICMJE Not Provided
Actual Primary Completion Date December 2015   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study:All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00779194
Other Study ID Numbers  ICMJE IRB#5658
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Andras Perl, MD, Ph.D, State University of New York - Upstate Medical University
Study Sponsor  ICMJE State University of New York - Upstate Medical University
Collaborators  ICMJE Pfizer
Investigators  ICMJE Not Provided
PRS Account State University of New York - Upstate Medical University
Verification Date October 2016

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP