Sirolimus Therapy for Idiopathic and Lupus Membranous Nephropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 16 December 2017
• Main ID: NCT00050713
• Date of registration: 17/12/2002
• Prospective Registration: Yes
• Primary sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Public title: Sirolimus Therapy for Idiopathic and Lupus Membranous Nephropathy
• Scientific title: Sirolimus Therapy in Idiopathic and Lupus Membranous Nephropathy
• Date of first enrolment: December 17, 2002
• Target sample size: 12
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT00050713
• Study type: Interventional
• Study design: Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United States

Contacts

• Name: Howard A Austin, M.D.
• Affiliation: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Key inclusion & exclusion criteria

- INCLUSION CRITERIA:

Ability and willingness to provide informed consent (adults greater than or equal to 18
years) or assent (children greater than or equal to 13 years) to all aspects of the study
after full information is provided.

Nephrotic range proteinuria that persists for at least 3 months.

Nephrotic range proteinuria that persists despite angiotensin antagonist therapy (ACE
inhibitor or ARB) for at least on month, unless intolerant. If patients have not started
ACE inhibitor therapy before they are referred to NIH, we plan to start lisinopril 5 mg
daily. We will advance the dose of ACE inhibitor as tolerated. Nephrotic range proteinuria,
defined as 24 hour urine protein excretion greater than or equal to 3.5 g/d, must be
documented in at least two 24 hour urine collections obtained during the month prior to
initiating sirolimus. Incomplete urine collections (based on inadequate creatinine
excretion) will be excluded.

Renal biopsy must reveal typical changes of membranous nephropathy by light and electron
microscopy.

SLE as defined by the presence of at least 4 criteria established by the American
Rheumatism Association (Lupus Membranous Nephropathy) or no evidence of a secondary form of
membranous nephropathy (Idiopathic Membranous Nephropathy).

EXCLUSION CRITERIA:

Intolerance to sirolimus or prior use of sirolimus for membranous nephropathy.

Estimated GFR less than 30 mL/min/1.73(2) (determined by the 5 variable version of the MDRD
Study prediction equation).

Immunosuppressive medications or experimental medications of any type during the two-month
period prior to initiating sirolimus, with the following two exceptions:

First, patients with lupus membranous nephropathy are permitted to have received modest
doses of corticosteroids (no more than the equivalent of prednisone 10mg/day) for control
of extra-renal manifestations of SLE during the two-month period prior to starting
sirolimus treatment.

Second, patients with worsening nephrotic syndrome (urine protein excretion rate doubles
+/or serum albumin decreases by greater than or equal to 1.0 g/ dL to less than 2.5 g/dL on
at least 2 determinations during or following a previous immunosuppressive treatment)
should fulfill the following criteria:

a) should be off prednisone for at least 2 weeks before performing the baseline evaluation
and starting sirolimus (if the patient has idiopathic membranous nephropathy): b) should be
on low-dose corticosteroids (no more than the equivalent of prednisone 10 mg/day) for at
least 2 weeks before performing the baseline evaluation and starting sirolimus (if the
patient lupus membranous nephropathy); c) should be off cyclosporine for at least 2 weeks
before performing the baseline evaluation and starting sirolimus; d) should be off
cyclophosphamide, chlorambucil, azathioprine and mycophenolate mofetil for at least 4 weeks
before performing the baseline evaluation and starting sirolimus;

Children less than 13.0 years.

Active acute or chronic infection requiring antimicrobial therapy or serious viral
infection (e.g. HIV, hepatitis, herpes zoster). Patients with a reactive PPD must have
completed a 6 to 12 month course of isoniazid as recommended by an infectious disease
consultant. Patients with a non-reactive PPD and non-reactive anergy panel must complete a
6 to 12 month course of isoniazid if recommended by an infectious disease consultant.

Pregnant women, nursing mothers or individuals (men and women) not practicing birth
control.

Uncontrolled hypertension, defined as BP greater than 140/90 on greater than 25% of
measurements. Blood pressures will be measured 3 times at each clinic visit after the
patient has sat quietly for at least 5 minutes. Thus at least 6 BP determinations will be
recorded prior to initiating sirolimus therapy.

Chronic liver disease sufficiently severe to impair sirolimus metabolism; this would
include prolonged pro-thrombin time. Patients with abnormal liver function tests will be
evaluated by the Hepatology Consult Service to determine whether protocol participation is
appropriate.

Basal thrombocytopenia less than 100,000 cells/microliters or absolute neutrophil count
less than 2000 cells/microliters or hematocrit less than 30.

Cancer diagnosis or cancer recurrence within the preceding 5 years, excluding basal cell
carcinoma of the skin.

Routine use of NSAIDS, defined as NSAID use more than two doses a week.

Clinically significant medical conditions, which in the opinion of the investigators, could
increase the subject s risk of participating in the study or could confound the
interpretation of the results of the study.



Age minimum: 13 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Membranous Glomerulonephritis

Lupus Membranous Nepropathy

Intervention(s)

Drug: Sirolimus

Primary Outcome(s)

The number of patients who are in 1) complete remission or 2) complete or partial remission. [Time Frame: 12 months after starting sirolimus]

Secondary Outcome(s)

Frequency of adverse effects

The number of patients who are in Complete or Partial Remission or Limited Response. [Time Frame: 12 months after starting sirolimus]

Secondary ID(s)

03-DK-0071

030071

Source(s) of Monetary Support

Please refer to primary and secondary sponsors