Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis

Scleroderma, Systemic Clinical Trial

Official title:

T Cell Immunity in Collagen Biosynthesis of Scleroderma

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00418132
• Other study ID #: K23AR002187
• Secondary ID: K23AR002187
• Status: Terminated
• Phase: Phase 1
• First received: January 3, 2007
• Last updated: March 10, 2016
• Start date: August 2000
• Est. completion date: October 2007

Study information

• Verified date: March 2016
• Source: New York University School of Medicine
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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-?, 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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Scleroderma, Diffuse
• Scleroderma, Systemic

Intervention

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 thalidomide
Participants will receive placebo thalidomide. The placebo dose will be increased through to Week 6.

Locations

Country	Name	City	State
United States	New York University School of Medicine General Clinical Research Center, Bellevue Hospital	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
New York University School of Medicine	National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Collagen mRNA levels in the skin		Measured at Weeks 16 and 48	No
Primary	In vivo collagen production		Measured at Weeks 16 and 48	No
Secondary	Immune function		Measured at Weeks 4, 16, and 48	No
Secondary	Clinical disease measures		Measured at Weeks 16 and 48	No
Secondary	Hypothalamic-Pituitary-Adrenal (HPA) axis measures		Measured at Weeks 16 and 48	No
Secondary	Safety measures		Measured at Weeks 4, 16, and 48	Yes