Pulmonary Involvement in Scleroderma: A Clinical Study of the Safety and Efficacy of Mycophenolate Mofetil in Scleroderma Patients With Lung Involvement

This study has been completed.
Sponsor:
Collaborator:
Roche Pharma AG
Information provided by (Responsible Party):
University of California, San Francisco
ClinicalTrials.gov Identifier:
NCT00333437
First received: June 2, 2006
Last updated: September 23, 2013
Last verified: September 2013
  Purpose

Researchers from the Division of Pulmonary and Critical Care Medicine at University of California, San Francisco (UCSF) are conducting a study to evaluate whether mycophenolate mofetil (an immunosuppressive medication, trade named CellCept) is safe and effective for preventing the lung damage from scleroderma from getting worse.


Condition Intervention
Scleroderma, Systemic
Drug: Mycophenolate mofetil

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pulmonary Involvement in Scleroderma: Safety and Efficacy of Mycophenolate Mofetil in Scleroderma Patients

Resource links provided by NLM:


Further study details as provided by University of California, San Francisco:

Primary Outcome Measures:
  • Mean Change From Baseline in Forced Vital Capacity (FVC) [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    compare pre- and post-therapy FVC (post- minus pre-). Forced vital capacity (FVC) is the volume of air (liters) that can forcibly be blown out after full inspiration.


Secondary Outcome Measures:
  • Mean Change in Bronchoalveolar Lavage (BAL) Components (Neutrophils, Eosinophils) [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    BAL samples were colleected from the affected lobe (as determined by lung CT scans) before beginning and after completing study therapy.

  • Change in Shortness of Breath (Self-reported) [ Time Frame: Baseline, 12 months ] [ Designated as safety issue: No ]
    Participants reported frequency of shortness of breath experienced with exertion

  • Mean Change in Six Minute Walk Distance [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    Comparison of 6-minute walk distance before beginning and after completing study therapy

  • Mean Change in Diffusion Capacity of the Lung for Carbon Monoxide (DLCO) [ Time Frame: 12 months ] [ Designated as safety issue: No ]
    DLCO was measured before beginning and after completion of study therapy


Enrollment: 7
Study Start Date: May 2006
Study Completion Date: January 2009
Primary Completion Date: January 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment
Mycophenolate Mofetil
Drug: Mycophenolate mofetil

Detailed Description:

The proposed study is designed to evaluate the safety and efficacy of mycophenolate mofetil (CellCept) for the treatment of symptomatic pulmonary alveolitis due to systemic sclerosis (SSc). This study utilizes a prospective, open-label, experimental design.

Primary Hypothesis: The alveolitis in patients with SSc, as defined by decreased forced vital capacity (FVC), bronchoalveolar lavage (BAL), and High Resolution Chest Tomography (HRCT) is responsive to 1 year of daily mycophenolate mofetil therapy.

Secondary Hypothesis: Quality of life, six-minute walk and single-breath diffusing capacity for carbon monoxide (DLCO) improve in patients with SSc mediated alveolitis after therapy with mycophenolate mofetil. This response to therapy is associated with a change in the inflammatory cytokine profile present in BAL fluid.

  Eligibility

Ages Eligible for Study:   21 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • To participate in this study, patients must first undergo a BAL and HRCT. To be eligible to undergo HRCT and BAL (under the purview of this trial), prospective patients must meet the following criteria:

    • Aged 21-70.
    • Negative pregnancy test (with a sensitivity of at least 50 mIU/mL) for females of child-bearing potential
    • All patients must fulfill the criteria for SSc by American College of Rheumatology (ACR) criteria (Subcommittee for Scleroderma Criteria 1980).
    • FVC < 85% of predicted.
    • SSc for no more than 7 years with onset defined as the date of the first non-Raynaud manifestation.
    • Patients may have limited (cutaneous thickening distal but not proximal to elbows and knees, with or without facial involvement) or diffuse (cutaneous thickening proximal to elbows and knees, often involving the chest or abdomen) cutaneous SSc (Medsger 1995).
    • Abnormal DLCO and abnormalities on the plain chest radiograph are not required, although a normal DLCO would be unusual in the face of significant ventilatory restriction due to SSc lung disease.
  • To be eligible to take study medication, the patient must meet not only the criteria above, but also must have ≥ 3.0% neutrophils or ≥ 2.0% eosinophils in screening BAL fluid and/or ground glass opacification on HRCT.
  • Women of childbearing potential should have a negative serum or urine pregnancy test with a sensitivity of at least 50 mIU/mL within 1 week before beginning therapy. CellCept therapy will not be initiated until a report of a negative pregnancy test has been obtained.
  • Effective contraception must be used before beginning CellCept therapy, during therapy, and for 6 weeks following discontinuation of therapy, even where there has been a history of infertility, unless due to hysterectomy. Two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method. If pregnancy does occur during treatment, the physician and patient should discuss the desirability of continuing the pregnancy.

Exclusion Criteria:

  • FVC < 45% of predicted or DLCO (corrected for hemoglobin [Hgb] but not for alveolar volume) < 35% of predicted (suggestive of severe, probably irreparable, disease).
  • Leukopenia (white blood cell count < 4000) or thrombocytopenia (platelet count < 100,000).
  • Serum creatinine ≥ 2.0 mg/dl.
  • Pregnancy, breast feeding, unreliability, drug abuse, or chronic debilitating disease.
  • Uncontrolled congestive heart failure.
  • Active infection of the lung, or elsewhere, whose management would be compromised by mycophenolate mofetil.
  • Prior treatment for alveolitis with mycophenolate mofetil or prior or current treatment for alveolitis with: D-penicillamine, methotrexate, colchicine, Potaba, or azathioprine.
  • Other serious concomitant medical illness (e.g., cancer).
  • Forced expiratory volume in 1 second (FEV1)/FVC ratio < 65%.
  • If of childbearing potential, failure regularly to be employing two reliable means of contraception (i.e., condom, abstinence, intrauterine device (IUD), tubal ligation, vasectomy)
  • Pulmonary hypertension (defined as an estimated systolic blood pressure (SBP) ≥ 35 mmHg measured by echocardiogram).
  • Smoking of cigars, pipes, or cigarettes during the past 6 months.
  • Clinically significant abnormalities on chest x-ray or HRCT scan other than interstitial lung disease (e.g., lung mass, evidence of active pulmonary infection).
  • Use of prednisone (or equivalent) in doses > 10 mg per day.
  • Does not have ≥ 3.0% neutrophils or ≥ 2.0% eosinophils on screening BAL fluid and does not have ground glass opacification on HRCT.
  • Unable to take oral medication.
  • Not able to comply with study procedures in the opinion of the investigator.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00333437

Locations
United States, California
UCSF, 400 Parnassus Ave
San Francisco, California, United States, 94143
Sponsors and Collaborators
University of California, San Francisco
Roche Pharma AG
Investigators
Principal Investigator: Jeffrey A Golden, MD University of California, San Francisco
  More Information

Additional Information:
No publications provided

Responsible Party: University of California, San Francisco
ClinicalTrials.gov Identifier: NCT00333437     History of Changes
Other Study ID Numbers: CEL371
Study First Received: June 2, 2006
Results First Received: May 6, 2013
Last Updated: September 23, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, San Francisco:
Scleroderma, Systemic

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Localized
Scleroderma, Systemic
Connective Tissue Diseases
Skin Diseases
Mycophenolate mofetil
Mycophenolic Acid
Antibiotics, Antineoplastic
Antineoplastic Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014