Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis

This study has been terminated.
(Study terminated early due to difficulties in subject recruitment)
Sponsor:
Collaborator:
Information provided by:
New York University School of Medicine
ClinicalTrials.gov Identifier:
NCT00418132
First received: January 3, 2007
Last updated: February 28, 2013
Last verified: February 2013
  Purpose

Progressive systemic sclerosis (SSc) is an immune-based disease that causes abnormal connective tissue growth of the skin and internal organs. At this point, there are no effective therapies for treating SSc. Thalidomide is a medication that has been shown to stimulate an immune response that reduces the body's synthesis of collagen, the main component of connective tissue. This study will determine the effectiveness of thalidomide in treating adults with SSc.


Condition Intervention Phase
Scleroderma, Systemic
Drug: Thalidomide
Drug: Placebo thalidomide
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: T Cell Immunity in Collagen Biosynthesis of Scleroderma

Resource links provided by NLM:


Further study details as provided by New York University School of Medicine:

Primary Outcome Measures:
  • Collagen mRNA levels in the skin [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
  • In vivo collagen production [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Immune function [ Time Frame: Measured at Weeks 4, 16, and 48 ] [ Designated as safety issue: No ]
  • Clinical disease measures [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
  • Hypothalamic-Pituitary-Adrenal (HPA) axis measures [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
  • Safety measures [ Time Frame: Measured at Weeks 4, 16, and 48 ] [ Designated as safety issue: Yes ]

Enrollment: 30
Study Start Date: August 2000
Study Completion Date: October 2007
Arms Assigned Interventions
Experimental: 1
Participants will receive thalidomide.
Drug: Thalidomide
Thalidomide at a dose of 50 mg/day. The dose will be increased to 100 mg/day at Week 2, then to 200 mg/day at Week 4, and finally to 300 mg/day at Week 6.
Placebo Comparator: 2
Participants will receive placebo thalidomide.
Drug: Placebo thalidomide
Participants will receive placebo thalidomide. The placebo dose will be increased through to Week 6.

Detailed Description:

Progressive systemic sclerosis (SSc), also known as scleroderma, is a disease of the body's connective tissue. It is characterized by fibrosis of the skin, or formation of scar-like tissue, resulting in progressively increased restriction of joint range of motion. Fibrosis of internal organs also occurs, leading to irregular heart rhythms, acid reflux, and respiratory problems. Unfortunately, no therapies have been developed to effectively treat SSc.

The disease is believed to be an immunological disorder that affects T-helper type 2 (Th2) cells, which stimulate the production of antibodies and interleukin-4 (IL-4), a protein with profibrotic properties. T-helper type 1 (Th1) cells produce interferon-γ (IFN-γ), a protein that prevents fibroblast production of collagen, a primary component of the body's connective tissue. It is possible that shifting the disease's target from the Th2 cells to the Th1 cells may decrease collagen production, and thereby reduce fibrosis. Thalidomide is an immune modulatory drug that has been shown to stimulate production of Th1 cells. This study will evaluate the effectiveness of thalidomide in treating adults with SSc.

Following screening procedures, participants in this 48-week, double-blind study will be randomly assigned to receive placebo or thalidomide at a dose of 50 mg/day. The thalidomide dose will be increased to 100 mg/day at Week 2, then to 200 mg/day at Week 4, and finally to 300 mg/day at Week 6. Participants who experience dose intolerance will immediately switch to the previously tolerated dose. Inpatient hospital visits lasting 2 days will occur at the beginning of the study before starting thalidomide treatment and at Weeks 16 and 48. Assessments and procedures at these visits will include blood and urine collection, a physical exam, a chest X-ray, an electrocardiogram, a skin biopsy, and various questionnaires. Outpatient study visits will occur at Weeks 2, 4, 6, 8, 12, 18, 20 and then every 4 weeks until Week 44. Assessments will include measures of immune function, clinical disease, hypothalamic-pituitary-adrenal axis, and safety. Following the Week 48 inpatient visit, thalidomide will be tapered off over a 2-week period for all participants.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Diagnosis of scleroderma
  • Agrees to use an effective form of contraception for 1 month prior to study entry, throughout the study, and for 60 days after completing the study
  • Positive serum anti-nuclear antibody titer

Exclusion Criteria:

  • Systemic sclerosis-like illnesses associated with environmental, ingested, or injected agents or with other connective tissue diseases
  • Significant existing damage to any of the following internal organs:

    • Kidneys, defined as a serum creatinine level greater than 2 mg/dl or renal crisis
    • Lungs, defined as needing supplemental oxygen
    • Heart, defined as left ventricular ejection fraction less than or equal to 40%
    • Gut, defined as pseudo-obstruction or malabsorption requiring total parental nutrition
  • Concurrent interventional therapy that might independently influence the outcome of this trial (e.g., D-penicillamine, cyclosporine, interferon-γ, methotrexate, or photophorosis)
  • Clinically significant and inadequately medically treated concurrent endocrine, blood, liver, lung, or kidney diseases
  • Pregnant
  • Recent drug or alcohol abuse
  • Documented noncompliance
  • Significant psychiatric history
  • Therapy with another investigational drug within 4 weeks prior to study entry
  • Screening laboratory results exceeding the following limits: hemoglobin level less than 7 gm/dl; white blood cell level less than 3,000/nl; platelet count less than 50/nl; alanine aminotransferase (ALT) level greater than 65 U/L; creatinine level greater than 2 mg/dl
  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: NCT00418132

Locations
United States, New York
New York University School of Medicine General Clinical Research Center, Bellevue Hospital
New York, New York, United States, 10016
Sponsors and Collaborators
New York University School of Medicine
Investigators
Principal Investigator: Stephen J. Oliver, MD New York University School of Medicine
  More Information

No publications provided

Responsible Party: Stephen J. Oliver, MD, New York University School of Medicine
ClinicalTrials.gov Identifier: NCT00418132     History of Changes
Other Study ID Numbers: K23 AR002187, K23AR002187
Study First Received: January 3, 2007
Last Updated: February 28, 2013
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by New York University School of Medicine:
SSc
Systemic Sclerosis
Progressive Systemic Sclerosis

Additional relevant MeSH terms:
Scleroderma, Diffuse
Scleroderma, Systemic
Connective Tissue Diseases
Skin Diseases
Thalidomide
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Anti-Bacterial Agents
Anti-Infective Agents
Antineoplastic Agents
Growth Inhibitors
Growth Substances
Immunologic Factors
Immunosuppressive Agents
Leprostatic Agents
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014