Back to results

Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II) (SLSII)

Primary Purpose

Scleroderma, Interstitial Lung Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Mycophenolate mofetil

Cyclophosphamide

Placebo

About this trial

This is an interventional treatment trial for Scleroderma focused on measuring Systemic Sclerosis, Mycophenolate Mofetil, Cyclophosphamide, High Resolution Computerized Tomography, Pulmonary Function, Dyspnea, Health Related Quality of Life

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

The presence of either 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) scleroderma, as determined by American College of Rheumatology criteria
Dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index)
FVC less than or equal to 80 percent of predicted value at screening and less than or equal to 85 percent predicted at baseline
Onset of the first non-Raynaud manifestation of SSc within the prior 84 months
Presence of any ground glass opacification on thoracic high resolution computerized tomography (HRCT)
Repeat FVC at the baseline visit (Visit 2) within 10 percent of the FVC measured at screening and less than or equal to 85 percent predicted.

Exclusion Criteria:

FVC less than 45 percent of predicted value at either screening or baseline
Carbon monoxide diffusing capacity (DLCO) (HBg-corrected) less than 30 percent of predicted value and less than 40 percent of predicted when documentation of pulmonary artery pressures by echocardiogram, right heart catheterization or magnetic resonance imaging identifies clinically significant pulmonary hypertension. All participants with a DLCO less than 40 percent predicted must have documentation of pulmonary artery pressures in order to be considered for inclusion.
FEV1/FVC ratio less than 65 percent at either screening or baseline
Clinically significant abnormalities on HRCT not attributable to scleroderma
Diagnosis of clinically significant resting pulmonary hypertension requiring treatment, as ascertained before study evaluation or as part of a standard of care clinical assessment performed outside of the study protocol
Persistent unexplained hematuria (more than 10 red blood cells per high-power field [RBCs/hpf])
History of persistent leukopenia (white blood cell count less than 4000) or thrombocytopenia (platelet count less than 150,000)
Clinically significant anemia (less than 10g/dl)
Baseline liver function test (LFTs) or bilirubin more than 1.5 times the upper limit of normal, other than that due to Gilbert's disease
Concomitant and present use of captopril
Serum creatinine more than 2.0mg/dL
Uncontrolled congestive heart failure
Pregnancy (documented by urine pregnancy test) and/or breast feeding
Prior use of oral CYC or MMF for more than 8 weeks or the receipt of more than two intravenous doses of CYC in the past
Use of CYC and/or MMF in the 30 days before random assignment
Active infection (lung or elsewhere) whose management would be compromised by CYC or MMF
Other serious concomitant medical illness (e.g., cancer), chronic debilitating illness (other than scleroderma), or unreliability or drug abuse that might compromise the patient's participation in the study
Current use, or use within the 30 days prior to random assignment, of prednisone (or equivalent) in doses of more than 10 mg/day
If of child bearing potential (a female participant <55 years of age who has not been postmenopausal for > 5 years and who has not had a hysterectomy and/or oophorectomy), failure to employ two reliable means of contraception (which may include surgical sterilization, barrier methods, spermicidals, intrauterine devices, and/or hormonal contraception).
Use of contraindicated medications; more information on this criterion can be found in the study protocol
Smoking of cigars, pipes, or cigarettes in the 6 months before study entry
Use of medications with putative disease-modifying properties within the past month (e.g., D-penicillamine, azathioprine, methotrexate, Potaba)

Sites / Locations

David Geffen School of Medicine at UCLA
University of California, San Francisco
National Jewish Health
Georgetown University School of Medicine
Feinberg School of Medicine, Northwestern University
University of Illinois at Chicago, College of Medicine
Johns Hopkins University School of Medicine
Boston University School of Medicine
University of Michigan Medical School
University of Minnesota
University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School
Medical University of South Carolina
University of Texas Medical School at Houston
University of Utah

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

Mycophenolate Arm

Cyclophosphamide Arm

Arm Description

Participants will receive oral mycophenolate mofetil for 2 years.

Participants will receive oral cyclophosphamide for 1 year, followed by placebo for 1 year.

Outcomes

Primary Outcome Measures

Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

The primary outcome is the course over time from baseline to 24 months for the FVC %-predicted. The FVC %-predicted represents the adjusted volume of air (adjusted as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity) that can be forcibly exhaled from the lungs after taking the deepest breath possible. The FVC %-predicted is reduced in patients with interstitial lung disease and is used as a measure of lung involvement and disease severity.

Secondary Outcome Measures

Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

The TLC represents the total volume of air within the lung after taking the deepest breath possible and the TLC %-predicted represents the TLC expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity. The TLC %-predicted is reduced in patients with interstitial lung disease and is used as a measure of disease severity.

Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

The DLCO is a pulmonary function test that measures the capacity for the lung to carry out gas exchange between the inhaled breath and the pulmonary capillary blood vessels and the DLCO %-predicted represents the DLCO expressed as a percentage of the expected normal valued based on the participant's age, height, gender and ethnicity. The DLCO %-predicted is reduced in patients with interstitial lung disease and is used as a measure of disease severity.

Fibrosis Score, as Measured by Thoracic High Resolution Computerized Tomography (HRCT)

Imaging of the whole lung (WL) is performed using a volumetric high resolution computerized tomography (HRCT) scan, which is then analyzed using a computer algorithm to determine the percentage of overall pixels exhibiting features characteristic for quantitative lung fibrosis (QLF). Higher percentages for QLF-WL therefore represent greater involvement by lung fibrosis.

Transitional Dyspnea Index Score

Change in breathlessness was assessed using the Transitional Dyspnea Index, which compares current symptoms to those at baseline. Total score ranges from - 9 to + 9. The lower the score, the more deterioration in severity of dyspnea.

Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI)

The HAQ-DI asks questions related to 8 activity domains (dressing, arising, eating, walking, hygiene, reach, grip, and common daily activities) with the patient's capacity to carry out each activity scored from 0 to 3. Scores across all domains are averaged and a higher score represents greater disability.

Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS)

Skin thickness is quantified using the modified Rodnan measurement method (mRSS), with a scale that ranges from 0 (no skin involvement) to a maximum of 51. The reported skin score is determined by a clinical assessment of skin thickness, which is performed by a trained reader, and represents the sum of individual assessments that are made in each of 17 body areas. Each area is given a score in the range of 0-3 (0 = normal; 1= mild thickness; 2 = moderate; 3 = severe thickness). A higher score represents more severe skin involvement.

Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death

Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure.

The number of participants who remained in the study at the listed time points are reported

Full Information

NCT ID

NCT00883129

First Posted

April 16, 2009

Last Updated

February 6, 2017

Sponsor

Michael Roth

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Hoffmann-La Roche

1. Study Identification

Unique Protocol Identification Number

NCT00883129

Brief Title

Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)

Acronym

SLSII

Official Title

Mycophenolate vs. Oral Cyclophosphamide in Scleroderma Interstitial Lung Disease (Scleroderma Lung Study II)

Study Type

Interventional

2. Study Status

Record Verification Date

February 2017

Overall Recruitment Status

Completed

Study Start Date

September 2009 (undefined)

Primary Completion Date

January 2015 (Actual)

Study Completion Date

November 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Michael Roth

Collaborators

National Heart, Lung, and Blood Institute (NHLBI), Hoffmann-La Roche

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

Scleroderma is a rare, long-term autoimmune disease in which normal tissue is replaced with dense, thick fibrous tissue. Normally, the immune system helps defend the body against disease and infection. In people with scleroderma, the immune system triggers fibroblast cells to produce too much of the protein collagen. The extra collagen becomes deposited in the skin and organs, causing hardening and thickening that is similar to the scarring process. Although scleroderma most often affects the skin, it also can affect other parts of the body, including the lungs, and in its most severe forms scleroderma can be life-threatening. Scleroderma-related interstitial lung disease is one example of a life-threatening scleroderma condition. In people with symptomatic scleroderma-related interstitial lung disease, scarring occurs in the delicate lung tissue, compromising lung function. The purpose of this study is to determine whether people with symptomatic scleroderma-related interstitial lung disease experience more respiratory benefits from treatment with a 2-year course of mycophenolate mofetil or treatment with a 1-year course of oral cyclophosphamide.

Detailed Description

Interstitial lung disease describes a condition in which the lung tissue has become scarred or inflamed. Interstitial lung disease caused by scleroderma, specifically seen as progressive pulmonary fibrosis, occurs in approximately 40 percent of patients with scleroderma and has emerged as the leading overall cause of death. In a previous study, the Scleroderma Lung Study I (SLS I), investigators evaluated a 1-year cyclophosphamide (CYC) treatment for people with scleroderma-related interstitial lung disease. The study results demonstrated statistically significant improvements in forced vital capacity, total lung capacity, dyspnea, Rodnan skin scores, and several measures of quality of life. However, when patients were followed for another year after completing their CYC therapy, the beneficial effects of CYC waned and were no longer significant by the 24-month follow-up. Preliminary information suggests that an alternative immunosuppressive medication, mycophenolate mofetil (MMF), may be effective in treating this disease, be given for longer periods, and result in fewer side effects. This study, the Scleroderma Lung Study II (SLS II), will compare the safety and efficacy of a 2-year treatment with MMF versus a 1-year treatment with CYC. Specifically, investigators will determine whether MMF produces similar or better improvements in lung capacity and fewer side effects throughout the entire 2-year period. Participation will include about 21 study visits over a 2-year period. Eligible participants will be randomly assigned to receive either MMF twice daily for 2 years or CYC once daily for 1 year, followed by placebo for 1 year. Blood and urine samples will be collected every 2 weeks for the first 2 months and then once a month for the remainder of the study. Every 3 months, participants will attend study visits that will include pulmonary function tests, blood and urine sampling, a physical exam, and questionnaires about current health and medications. At the final study visit, participants will also undergo a high resolution computerized tomography (HRCT) scan and possibly a punch biopsy.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Scleroderma, Interstitial Lung Disease

Keywords

Systemic Sclerosis, Mycophenolate Mofetil, Cyclophosphamide, High Resolution Computerized Tomography, Pulmonary Function, Dyspnea, Health Related Quality of Life

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

142 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Mycophenolate Arm

Arm Type

Experimental

Arm Description

Participants will receive oral mycophenolate mofetil for 2 years.

Arm Title

Cyclophosphamide Arm

Arm Type

Experimental

Arm Description

Participants will receive oral cyclophosphamide for 1 year, followed by placebo for 1 year.

Intervention Type

Drug

Intervention Name(s)

Mycophenolate mofetil

Other Intervention Name(s)

CellCept

Intervention Description

24 months of oral mycophenolate mofetil, up to a maximal dose of 1.5 grams twice daily as tolerated

Intervention Type

Drug

Intervention Name(s)

Cyclophosphamide

Other Intervention Name(s)

Cytoxan

Intervention Description

12 months of oral cyclophosphamide, up to a maximal dose of 2 mg/kg daily as tolerated

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

Sugar Pill

Intervention Description

12 months of placebo will be delivered to participants in the Cyclophosphamide arm during the second year in order to maintain the blind with the Mycophenolate arm, which receives drug for the entire 2 years.

Primary Outcome Measure Information:

Title

Forced Vital Capacity (FVC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

Description

Time Frame

Measured at study Baseline and Months 3, 6, 12, 15, 18, 21, and 24

Secondary Outcome Measure Information:

Title

Total Lung Capacity (TLC), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

Description

Time Frame

Measured at study entry and Months 6, 12, 18, and 24

Title

Single-breath Diffusing Capacity for Carbon Monoxide (DLCO), as a Percent of the Age, Height, Gender, and Ethnicity Adjusted Predicted Value

Description

Time Frame

Measured at study entry and Months 3, 6, 12, 15, 18, 21, and 24

Title

Fibrosis Score, as Measured by Thoracic High Resolution Computerized Tomography (HRCT)

Description

Time Frame

Measured at baseline and Month 24

Title

Transitional Dyspnea Index Score

Description

Time Frame

Measured at Months 6, 12, 18, and 24

Title

Health-related Quality of Life as Measured by the Patient Responses to the Health Assessment Questionnaire Disability Index (HAQ-DI)

Description

Time Frame

Measured at study entry and Months 3, 6, 9, 12, 15, 18, 21, and 24

Title

Skin Involvement, as Measured by the Modified Rodnam Skin Thickness Scores (mRSS)

Description

Time Frame

Measured at baseline and Months 3, 6, 9, 12, 15, 18, 21, and 24

Title

Toxicity, as Measured by Adverse Events, Serious Adverse Events, and Death

Time Frame

Measured throughout the 2-year study

Title

Tolerability, as Assessed by the Time to Withdrawal From the Study Drug or Meeting Protocol-defined Criteria for Treatment Failure.

Description

The number of participants who remained in the study at the listed time points are reported

Time Frame

Continuous assessment from randomization to 24 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: The presence of either 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) scleroderma, as determined by American College of Rheumatology criteria Dyspnea on exertion (grade 2 on the Magnitude of Task component of the Mahler Modified Dyspnea Index) FVC less than or equal to 80 percent of predicted value at screening and less than or equal to 85 percent predicted at baseline Onset of the first non-Raynaud manifestation of SSc within the prior 84 months Presence of any ground glass opacification on thoracic high resolution computerized tomography (HRCT) Repeat FVC at the baseline visit (Visit 2) within 10 percent of the FVC measured at screening and less than or equal to 85 percent predicted. Exclusion Criteria: FVC less than 45 percent of predicted value at either screening or baseline Carbon monoxide diffusing capacity (DLCO) (HBg-corrected) less than 30 percent of predicted value and less than 40 percent of predicted when documentation of pulmonary artery pressures by echocardiogram, right heart catheterization or magnetic resonance imaging identifies clinically significant pulmonary hypertension. All participants with a DLCO less than 40 percent predicted must have documentation of pulmonary artery pressures in order to be considered for inclusion. FEV1/FVC ratio less than 65 percent at either screening or baseline Clinically significant abnormalities on HRCT not attributable to scleroderma Diagnosis of clinically significant resting pulmonary hypertension requiring treatment, as ascertained before study evaluation or as part of a standard of care clinical assessment performed outside of the study protocol Persistent unexplained hematuria (more than 10 red blood cells per high-power field [RBCs/hpf]) History of persistent leukopenia (white blood cell count less than 4000) or thrombocytopenia (platelet count less than 150,000) Clinically significant anemia (less than 10g/dl) Baseline liver function test (LFTs) or bilirubin more than 1.5 times the upper limit of normal, other than that due to Gilbert's disease Concomitant and present use of captopril Serum creatinine more than 2.0mg/dL Uncontrolled congestive heart failure Pregnancy (documented by urine pregnancy test) and/or breast feeding Prior use of oral CYC or MMF for more than 8 weeks or the receipt of more than two intravenous doses of CYC in the past Use of CYC and/or MMF in the 30 days before random assignment Active infection (lung or elsewhere) whose management would be compromised by CYC or MMF Other serious concomitant medical illness (e.g., cancer), chronic debilitating illness (other than scleroderma), or unreliability or drug abuse that might compromise the patient's participation in the study Current use, or use within the 30 days prior to random assignment, of prednisone (or equivalent) in doses of more than 10 mg/day If of child bearing potential (a female participant <55 years of age who has not been postmenopausal for > 5 years and who has not had a hysterectomy and/or oophorectomy), failure to employ two reliable means of contraception (which may include surgical sterilization, barrier methods, spermicidals, intrauterine devices, and/or hormonal contraception). Use of contraindicated medications; more information on this criterion can be found in the study protocol Smoking of cigars, pipes, or cigarettes in the 6 months before study entry Use of medications with putative disease-modifying properties within the past month (e.g., D-penicillamine, azathioprine, methotrexate, Potaba)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Donald P. Tashkin, MD

Organizational Affiliation

University of California, Los Angeles

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Robert M. Elashoff, PhD

Organizational Affiliation

UCLA School of Public Health

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Michael D. Roth, MD

Organizational Affiliation

University of California, Los Angeles

Official's Role

Principal Investigator

Facility Information:

Facility Name

David Geffen School of Medicine at UCLA

City

Los Angeles

State/Province

California

ZIP/Postal Code

90095

Country

United States

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Facility Name

National Jewish Health

City

Denver

State/Province

Colorado

ZIP/Postal Code

80206

Country

United States

Facility Name

Georgetown University School of Medicine

City

Washington

State/Province

District of Columbia

ZIP/Postal Code

20057

Country

United States

Facility Name

Feinberg School of Medicine, Northwestern University

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60611

Country

United States

Facility Name

University of Illinois at Chicago, College of Medicine

City

Chicago

State/Province

Illinois

ZIP/Postal Code

60612

Country

United States

Facility Name

Johns Hopkins University School of Medicine

City

Baltimore

State/Province

Maryland

ZIP/Postal Code

21205

Country

United States

Facility Name

Boston University School of Medicine

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02118

Country

United States

Facility Name

University of Michigan Medical School

City

Ann Arbor

State/Province

Michigan

ZIP/Postal Code

48109

Country

United States

Facility Name

University of Minnesota

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55454

Country

United States

Facility Name

University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School

City

New Brunswick

State/Province

New Jersey

ZIP/Postal Code

08854

Country

United States

Facility Name

Medical University of South Carolina

City

Charleston

State/Province

South Carolina

ZIP/Postal Code

29425

Country

United States

Facility Name

University of Texas Medical School at Houston

City

Houston

State/Province

Texas

ZIP/Postal Code

77225

Country

United States

Facility Name

University of Utah

City

Salt Lake City

State/Province

Utah

ZIP/Postal Code

84132

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

18620121

Citation

Kim HJ, Li G, Gjertson D, Elashoff R, Shah SK, Ochs R, Vasunilashorn F, Abtin F, Brown MS, Goldin JG. Classification of parenchymal abnormality in scleroderma lung using a novel approach to denoise images collected via a multicenter study. Acad Radiol. 2008 Aug;15(8):1004-16. doi: 10.1016/j.acra.2008.03.011.

Results Reference

background

PubMed Identifier

17124698

Citation

Elashoff RM, Li G, Li N. An approach to joint analysis of longitudinal measurements and competing risks failure time data. Stat Med. 2007 Jun 30;26(14):2813-35. doi: 10.1002/sim.2749.

Results Reference

background

PubMed Identifier

18162112

Citation

Elashoff RM, Li G, Li N. A joint model for longitudinal measurements and survival data in the presence of multiple failure types. Biometrics. 2008 Sep;64(3):762-771. doi: 10.1111/j.1541-0420.2007.00952.x. Epub 2007 Dec 20.

Results Reference

background

PubMed Identifier

19197956

Citation

Li N, Elashoff RM, Li G. Robust joint modeling of longitudinal measurements and competing risks failure time data. Biom J. 2009 Feb;51(1):19-30. doi: 10.1002/bimj.200810491.

Results Reference

background

PubMed Identifier

19286849

Citation

Hant FN, Ludwicka-Bradley A, Wang HJ, Li N, Elashoff R, Tashkin DP, Silver RM; Scleroderma Lung Study Research Group. Surfactant protein D and KL-6 as serum biomarkers of interstitial lung disease in patients with scleroderma. J Rheumatol. 2009 Apr;36(4):773-80. doi: 10.3899/jrheum.080633. Epub 2009 Mar 13.

Results Reference

background

PubMed Identifier

21050542

Citation

Kim HG, Tashkin DP, Clements PJ, Li G, Brown MS, Elashoff R, Gjertson DW, Abtin F, Lynch DA, Strollo DC, Goldin JG. A computer-aided diagnosis system for quantitative scoring of extent of lung fibrosis in scleroderma patients. Clin Exp Rheumatol. 2010 Sep-Oct;28(5 Suppl 62):S26-35. Epub 2010 Nov 3.

Results Reference

background

PubMed Identifier

21531236

Citation

Furst DE, Tseng CH, Clements PJ, Strange C, Tashkin DP, Roth MD, Khanna D, Li N, Elashoff R, Schraufnagel DE; Scleroderma Lung Study. Adverse events during the Scleroderma Lung Study. Am J Med. 2011 May;124(5):459-67. doi: 10.1016/j.amjmed.2010.12.009.

Results Reference

background

PubMed Identifier

21547897

Citation

Roth MD, Tseng CH, Clements PJ, Furst DE, Tashkin DP, Goldin JG, Khanna D, Kleerup EC, Li N, Elashoff D, Elashoff RM; Scleroderma Lung Study Research Group. Predicting treatment outcomes and responder subsets in scleroderma-related interstitial lung disease. Arthritis Rheum. 2011 Sep;63(9):2797-808. doi: 10.1002/art.30438.

Results Reference

background

PubMed Identifier

21618205

Citation

Khanna D, Tseng CH, Farmani N, Steen V, Furst DE, Clements PJ, Roth MD, Goldin J, Elashoff R, Seibold JR, Saggar R, Tashkin DP. Clinical course of lung physiology in patients with scleroderma and interstitial lung disease: analysis of the Scleroderma Lung Study Placebo Group. Arthritis Rheum. 2011 Oct;63(10):3078-85. doi: 10.1002/art.30467.

Results Reference

background

PubMed Identifier

21927793

Citation

Kim HJ, Brown MS, Elashoff R, Li G, Gjertson DW, Lynch DA, Strollo DC, Kleerup E, Chong D, Shah SK, Ahmad S, Abtin F, Tashkin DP, Goldin JG. Quantitative texture-based assessment of one-year changes in fibrotic reticular patterns on HRCT in scleroderma lung disease treated with oral cyclophosphamide. Eur Radiol. 2011 Dec;21(12):2455-65. doi: 10.1007/s00330-011-2223-2. Epub 2011 Sep 17.

Results Reference

background

PubMed Identifier

22156609

Citation

Theodore AC, Tseng CH, Li N, Elashoff RM, Tashkin DP. Correlation of cough with disease activity and treatment with cyclophosphamide in scleroderma interstitial lung disease: findings from the Scleroderma Lung Study. Chest. 2012 Sep;142(3):614-621. doi: 10.1378/chest.11-0801.

Results Reference

background

PubMed Identifier

16790698

Citation

Tashkin DP, Elashoff R, Clements PJ, Goldin J, Roth MD, Furst DE, Arriola E, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M; Scleroderma Lung Study Research Group. Cyclophosphamide versus placebo in scleroderma lung disease. N Engl J Med. 2006 Jun 22;354(25):2655-66. doi: 10.1056/NEJMoa055120.

Results Reference

result

PubMed Identifier

15692967

Citation

Khanna D, Clements PJ, Furst DE, Chon Y, Elashoff R, Roth MD, Sterz MG, Chung J, FitzGerald JD, Seibold JR, Varga J, Theodore A, Wigley FM, Silver RM, Steen VD, Mayes MD, Connolly MK, Fessler BJ, Rothfield NF, Mubarak K, Molitor J, Tashkin DP; Scleroderma Lung Study Group. Correlation of the degree of dyspnea with health-related quality of life, functional abilities, and diffusing capacity for carbon monoxide in patients with systemic sclerosis and active alveolitis: results from the Scleroderma Lung Study. Arthritis Rheum. 2005 Feb;52(2):592-600. doi: 10.1002/art.20787.

Results Reference

result

PubMed Identifier

17469162

Citation

Khanna D, Yan X, Tashkin DP, Furst DE, Elashoff R, Roth MD, Silver R, Strange C, Bolster M, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel DE, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Clements PJ; Scleroderma Lung Study Group. Impact of oral cyclophosphamide on health-related quality of life in patients with active scleroderma lung disease: results from the scleroderma lung study. Arthritis Rheum. 2007 May;56(5):1676-84. doi: 10.1002/art.22580.

Results Reference

result

PubMed Identifier

17485423

Citation

Clements PJ, Roth MD, Elashoff R, Tashkin DP, Goldin J, Silver RM, Sterz M, Seibold JR, Schraufnagel D, Simms RW, Bolster M, Wise RA, Steen V, Mayes MD, Connelly K, Metersky M, Furst DE; Scleroderma Lung Study Group. Scleroderma lung study (SLS): differences in the presentation and course of patients with limited versus diffuse systemic sclerosis. Ann Rheum Dis. 2007 Dec;66(12):1641-7. doi: 10.1136/ard.2007.069518. Epub 2007 May 7.

Results Reference

result

PubMed Identifier

17717203

Citation

Tashkin DP, Elashoff R, Clements PJ, Roth MD, Furst DE, Silver RM, Goldin J, Arriola E, Strange C, Bolster MB, Seibold JR, Riley DJ, Hsu VM, Varga J, Schraufnagel D, Theodore A, Simms R, Wise R, Wigley F, White B, Steen V, Read C, Mayes M, Parsley E, Mubarak K, Connolly MK, Golden J, Olman M, Fessler B, Rothfield N, Metersky M, Khanna D, Li N, Li G; Scleroderma Lung Study Research Group. Effects of 1-year treatment with cyclophosphamide on outcomes at 2 years in scleroderma lung disease. Am J Respir Crit Care Med. 2007 Nov 15;176(10):1026-34. doi: 10.1164/rccm.200702-326OC. Epub 2007 Aug 23.

Results Reference

result

PubMed Identifier

17901414

Citation

Strange C, Bolster MB, Roth MD, Silver RM, Theodore A, Goldin J, Clements P, Chung J, Elashoff RM, Suh R, Smith EA, Furst DE, Tashkin DP; Scleroderma Lung Study Research Group. Bronchoalveolar lavage and response to cyclophosphamide in scleroderma interstitial lung disease. Am J Respir Crit Care Med. 2008 Jan 1;177(1):91-8. doi: 10.1164/rccm.200705-655OC. Epub 2007 Sep 27.

Results Reference

result

PubMed Identifier

18641099

Citation

Goldin JG, Lynch DA, Strollo DC, Suh RD, Schraufnagel DE, Clements PJ, Elashoff RM, Furst DE, Vasunilashorn S, McNitt-Gray MF, Brown MS, Roth MD, Tashkin DP; Scleroderma Lung Study Research Group. High-resolution CT scan findings in patients with symptomatic scleroderma-related interstitial lung disease. Chest. 2008 Aug;134(2):358-367. doi: 10.1378/chest.07-2444. Epub 2008 Jul 18.

Results Reference

result

PubMed Identifier

19776222

Citation

Khanna D, Tseng CH, Furst DE, Clements PJ, Elashoff R, Roth M, Elashoff D, Tashkin DP; for Scleroderma Lung Study Investigators. Minimally important differences in the Mahler's Transition Dyspnoea Index in a large randomized controlled trial--results from the Scleroderma Lung Study. Rheumatology (Oxford). 2009 Dec;48(12):1537-40. doi: 10.1093/rheumatology/kep284. Epub 2009 Sep 23.

Results Reference

result

PubMed Identifier

19892673

Citation

Goldin J, Elashoff R, Kim HJ, Yan X, Lynch D, Strollo D, Roth MD, Clements P, Furst DE, Khanna D, Vasunilashorn S, Li G, Tashkin DP. Treatment of scleroderma-interstitial lung disease with cyclophosphamide is associated with less progressive fibrosis on serial thoracic high-resolution CT scan than placebo: findings from the scleroderma lung study. Chest. 2009 Nov;136(5):1333-1340. doi: 10.1378/chest.09-0108.

Results Reference

result

PubMed Identifier

20740615

Citation

Au K, Mayes MD, Maranian P, Clements PJ, Khanna D, Steen VD, Tashkin D, Roth MD, Elashoff R, Furst DE. Course of dermal ulcers and musculoskeletal involvement in systemic sclerosis patients in the scleroderma lung study. Arthritis Care Res (Hoboken). 2010 Dec;62(12):1772-8. doi: 10.1002/acr.20320.

Results Reference

result

PubMed Identifier

33350170

Citation

Assassi S, Li N, Volkmann ER, Mayes MD, Runger D, Ying J, Roth MD, Hinchcliff M, Khanna D, Frech T, Clements PJ, Furst DE, Goldin J, Bernstein EJ, Castelino FV, Domsic RT, Gordon JK, Hant FN, Shah AA, Shanmugam VK, Steen VD, Elashoff RM, Tashkin DP. Predictive Significance of Serum Interferon-Inducible Protein Score for Response to Treatment in Systemic Sclerosis-Related Interstitial Lung Disease. Arthritis Rheumatol. 2021 Jun;73(6):1005-1013. doi: 10.1002/art.41627. Epub 2021 Apr 20.

Results Reference

derived

PubMed Identifier

31430058

Citation

Kim GHJ, Tashkin DP, Lo P, Brown MS, Volkmann ER, Gjertson DW, Khanna D, Elashoff RM, Tseng CH, Roth MD, Goldin JG. Using Transitional Changes on High-Resolution Computed Tomography to Monitor the Impact of Cyclophosphamide or Mycophenolate Mofetil on Systemic Sclerosis-Related Interstitial Lung Disease. Arthritis Rheumatol. 2020 Feb;72(2):316-325. doi: 10.1002/art.41085. Epub 2019 Dec 26.

Results Reference

derived

PubMed Identifier

30651141

Citation

Khanna D, Clements PJ, Volkmann ER, Wilhalme H, Tseng CH, Furst DE, Roth MD, Distler O, Tashkin DP. Minimal Clinically Important Differences for the Modified Rodnan Skin Score: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Arthritis Res Ther. 2019 Jan 16;21(1):23. doi: 10.1186/s13075-019-1809-y.

Results Reference

derived

PubMed Identifier

29099620

Citation

Kafaja S, Clements PJ, Wilhalme H, Tseng CH, Furst DE, Kim GH, Goldin J, Volkmann ER, Roth MD, Tashkin DP, Khanna D. Reliability and minimal clinically important differences of forced vital capacity: Results from the Scleroderma Lung Studies (SLS-I and SLS-II). Am J Respir Crit Care Med. 2018 Mar 1;197(5):644-652. doi: 10.1164/rccm.201709-1845OC. Epub 2017 Nov 3.

Results Reference

derived

PubMed Identifier

28544580

Citation

Namas R, Tashkin DP, Furst DE, Wilhalme H, Tseng CH, Roth MD, Kafaja S, Volkmann E, Clements PJ, Khanna D; Participants in the Scleroderma Lung Study I and members of the Scleroderma Lung Study II Research Group. Efficacy of Mycophenolate Mofetil and Oral Cyclophosphamide on Skin Thickness: Post Hoc Analyses From Two Randomized Placebo-Controlled Trials. Arthritis Care Res (Hoboken). 2018 Mar;70(3):439-444. doi: 10.1002/acr.23282. Epub 2018 Feb 9.

Results Reference

derived

PubMed Identifier

28038680

Citation

Volkmann ER, Tashkin DP, Roth MD, Clements PJ, Khanna D, Furst DE, Mayes M, Charles J, Tseng CH, Elashoff RM, Assassi S. Changes in plasma CXCL4 levels are associated with improvements in lung function in patients receiving immunosuppressive therapy for systemic sclerosis-related interstitial lung disease. Arthritis Res Ther. 2016 Dec 30;18(1):305. doi: 10.1186/s13075-016-1203-y.

Results Reference

derived

PubMed Identifier

28012804

Citation

Tashkin DP, Volkmann ER, Tseng CH, Roth MD, Khanna D, Furst DE, Clements PJ, Theodore A, Kafaja S, Kim GH, Goldin J, Ariolla E, Elashoff RM. Improved Cough and Cough-Specific Quality of Life in Patients Treated for Scleroderma-Related Interstitial Lung Disease: Results of Scleroderma Lung Study II. Chest. 2017 Apr;151(4):813-820. doi: 10.1016/j.chest.2016.11.052. Epub 2016 Dec 22.

Results Reference

derived

PubMed Identifier

27469583

Citation

Tashkin DP, Roth MD, Clements PJ, Furst DE, Khanna D, Kleerup EC, Goldin J, Arriola E, Volkmann ER, Kafaja S, Silver R, Steen V, Strange C, Wise R, Wigley F, Mayes M, Riley DJ, Hussain S, Assassi S, Hsu VM, Patel B, Phillips K, Martinez F, Golden J, Connolly MK, Varga J, Dematte J, Hinchcliff ME, Fischer A, Swigris J, Meehan R, Theodore A, Simms R, Volkov S, Schraufnagel DE, Scholand MB, Frech T, Molitor JA, Highland K, Read CA, Fritzler MJ, Kim GHJ, Tseng CH, Elashoff RM; Sclerodema Lung Study II Investigators. Mycophenolate mofetil versus oral cyclophosphamide in scleroderma-related interstitial lung disease (SLS II): a randomised controlled, double-blind, parallel group trial. Lancet Respir Med. 2016 Sep;4(9):708-719. doi: 10.1016/S2213-2600(16)30152-7. Epub 2016 Jul 25.

Results Reference

derived

PubMed Identifier

25452309

Citation

Tashkin DP, Volkmann ER, Tseng CH, Kim HJ, Goldin J, Clements P, Furst D, Khanna D, Kleerup E, Roth MD, Elashoff R. Relationship between quantitative radiographic assessments of interstitial lung disease and physiological and clinical features of systemic sclerosis. Ann Rheum Dis. 2016 Feb;75(2):374-81. doi: 10.1136/annrheumdis-2014-206076. Epub 2014 Dec 1.

Results Reference

derived

Learn more about this trial

Comparison of Therapeutic Regimens for Scleroderma Interstitial Lung Disease (The Scleroderma Lung Study II)

We'll reach out to this number within 24 hrs