Scleroderma, SystemicPhase 1NCT00418132
Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis
A Phase 1 study testing Thalidomide in people with Scleroderma, Systemic, run by NYU Langone Health at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Scleroderma, Systemic
- What is being tested?
- Thalidomide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2000to Oct 2007
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
New York University School of Medicine General Clinical Research Center, Bellevue Hospital
New York, New York, 10016
About this study
Official title: T Cell Immunity in Collagen Biosynthesis of Scleroderma
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.
Read the 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.
- Conditions
- Scleroderma, Systemic
- Being tested
- Thalidomide, Placebo thalidomide
- Keywords
- SSc, Systemic Sclerosis, Progressive Systemic Sclerosis
- Medical subject headings
- Scleroderma, Systemic, Scleroderma, Diffuse
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ThalidomideDrug
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 thalidomideDrug
Participants will receive placebo thalidomide. The placebo dose will be increased through to Week 6.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Participants will receive thalidomide. Receives: Drug: Thalidomide |
| 2 | Placebo comparator | Participants will receive placebo thalidomide. Receives: Drug: Placebo thalidomide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Collagen mRNA levels in the skin
Measured: Measured at Weeks 16 and 48
In vivo collagen production
Measured: Measured at Weeks 16 and 48
Secondary outcomes (4)
Immune function
Measured: Measured at Weeks 4, 16, and 48
Clinical disease measures
Measured: Measured at Weeks 16 and 48
Hypothalamic-Pituitary-Adrenal (HPA) axis measures
Measured: Measured at Weeks 16 and 48
Safety measures
Measured: Measured at Weeks 4, 16, and 48
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jan 2007 (estimated)
- Study startAug 2000
- Study completionOct 2007
Why it stopped: Study terminated early due to difficulties in subject recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Scleroderma, SystemicStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Investigators
- Stephen J. Oliver, MD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00418132
- Sponsor's protocol ID
- K23AR002187
- Other IDs
- K23AR002187
- Status last verified
- Mar 2016
- First submitted
- 3 Jan 2007
- Last updated
- 11 Mar 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- T Cell Immunity in Collagen Biosynthesis of Scleroderma
- ClinicalTrials.gov ID
- NCT00418132
- Acronym / sponsor ID
- K23AR002187
- Conditions
- Scleroderma, Systemic
- Keywords
- SSc, Systemic Sclerosis, Progressive Systemic Sclerosis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Study terminated early due to difficulties in subject recruitment
- Enrolment
- 30 participants (actual)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
- Study start
- Aug 2000
- Study completion
- Oct 2007 (actual)
- First posted
- 4 Jan 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: ThalidomideParticipants will receive thalidomide. |
| 2 | Placebo comparator | Drug: Placebo thalidomideParticipants will receive placebo thalidomide. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (14 listed)
- 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:
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ThalidomideThalidomide 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. | Drug | 1 |
| Placebo thalidomideParticipants will receive placebo thalidomide. The placebo dose will be increased through to Week 6. | Drug | 2 |
Primary outcome
Collagen mRNA levels in the skin
Time frame: Measured at Weeks 16 and 48
In vivo collagen production
Time frame: Measured at Weeks 16 and 48
4 secondary outcomes
Immune function
Time frame: Measured at Weeks 4, 16, and 48
Clinical disease measures
Time frame: Measured at Weeks 16 and 48
Hypothalamic-Pituitary-Adrenal (HPA) axis measures
Time frame: Measured at Weeks 16 and 48
Safety measures
Time frame: Measured at Weeks 4, 16, and 48
Results and safety
The study was stopped early (reason given: Study terminated early due to difficulties in subject recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2016.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Stephen J. Oliver, MD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Thalidomide in people with Scleroderma, Systemic, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Mar 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Study terminated early due to difficulties in subject recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Collagen mRNA levels in the skin (time frame: Measured at Weeks 16 and 48). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2016.