Nephrogenic Systemic FibrosisPhase 3NSFNCT00981942
Treatment of Patients With Nephrogenic Systemic Fibrosis With Glivec
A Phase 3 study testing Imatinib mesylate (Glivec) in people with Nephrogenic Systemic Fibrosis, run by University of Aarhus at 2 sites in Denmark.
Trial summary
The investigators will study the effect of imatinib mesylate (Glivec) in treatment of moderate to severe nephrogenic systemic fibrosis (NSF). So far there is no evidence of adequately effective treatment options of NSF. Various treatments have been tried to stop the progressing disease. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Nephrogenic Systemic Fibrosis
- What is being tested?
- Imatinib mesylate (Glivec)
- Type of treatment
- Pill or oral medicine
- How many people
- 10 participants
- Where
- 2 sitesDenmark
- Study dates
- Sep 2009to Dec 2010
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age > 18 years
- Diagnosed with NSF
- mRodnan skin score => 20 or
- Rapid progression of the disease defined as a 50% increase in mRodnan skin score in less than 7 weeks or
- Progression of the fibrosis in the inner organs ex. the heart or the lungs, AND
- No absolute contraindications to the treatment
Who cannot join
- Known sensitivity to Imatinib mesylate or to any of its components
- Pregnant or lactating woman
- ALAT > 3 x upper limit of normal
- Severe congestive heart failure (NYHA Class III or IV)
Trial locations and contacts
2 sites in 1 country.
Denmark2 sites
Department of Dermatology
Aarhus, Aarhus, 8000
Department of Dermatology
Aarhus, 8000
About this study
Official title: An Open Label Clinical Trial of Imatinib Mesylate(Glivec)in Patients With Moderate to Severe Nephrogenic Systemic Fibrosis
The investigators will study the effect of imatinib mesylate (Glivec) in treatment of moderate to severe nephrogenic systemic fibrosis (NSF).
So far there is no evidence of adequately effective treatment options of NSF. Various treatments have been tried to stop the progressing disease. Corticosteroids, which suppress the early inflammatory stage of the disease, fail to halt disease progression.
Other immunosuppressive agents, photopheresis, and kidney transplantations are reported to be partly beneficial to the patients.
It has not been possible to confirm these findings in further studies because in photopheresis, and kidney transplantation, such effects are generally unreproducible.
Read the detailed description
NSF is a relatively newly defined fibrosing disease not described before 1997 where the Gadolinium-based contrast agents (GBCAs) were introduced in patients with kidney disease. The association between NSF and GBCA has in many studies shown to be very strong. Until recently, radiologists believed that commercially available GBCAs were safe to use whether the renal function was normal or not. Since the 1980s, >200 million patients have been given these agents. Lately, the occurrence of NSF, a relatively new chronic disorder, has given serious speculations about the safety of these drugs and has questioned their future use. First identified in 1997, but not described until 2000, NSF has been reported only in patients with acute or chronic severe renal insufficiency (with a glomerular filtration rate <30 ml/min/1.73 m2).
Fibrosis in the subcutis means that the skin hardens and loses flexibility. Hard dermal plaque changes often appear on legs, arms and abdomen together with dyspigmentation. As the lesions involve the deep part of the subcutis the muscles are often affected. Involvement of the joints leads to contractures and narrowing of movement. Patients with massive affection of the joints often end up with a zimmer frame or in a wheelchair. The connecting tissue in the inner vital organs may also be affected and NSF can accelerate the death of the patient. The retained gadolinium in lesions of NSF can be found years after administration.
Interestingly, a case report suggests beneficial effects of imatinib mesylate in two patients. Two other independent case reports also show promising results.
Imatinib mesylate inhibits several tyrosine kinases involved in the fibrotic reaction, which is one of the main pathogenetic components of NSF.
- Conditions
- Nephrogenic Systemic Fibrosis
- Being tested
- Imatinib mesylate (Glivec)
- Keywords
- Nephrogenic systemic fibrosis, Imatinib mesylate, Glivec, Gleevec
- Medical subject headings
- Nephrogenic Fibrosing Dermopathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Imatinib mesylate (Glivec)Drug
Also called Glivec, Gleevec
400 mg, one tablet daily for 12 or 24 weeks
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoints are skin fibrosis and joint mobility.
Measured: 16 weeks or 28 weeks
Secondary outcomes (1)
The secondary endpoint is and joint mobility.
Measured: 16 weeks or 28 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2009 (estimated)
- Study startSep 2009
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Nephrogenic Systemic FibrosisStudies of the same condition, open and under way.
- More trials run by University of AarhusThe 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 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Aarhus
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Anne B Olesen, MD,PhD, Principal investigator, Anne Braae Olesen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981942
- Sponsor's protocol ID
- 22505 TRE
- Acronym
- NSF
- Status last verified
- Jun 2012
- First submitted
- 21 Sep 2009
- Last updated
- 5 Jun 2012
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis. Arthritis Rheum. 2008 Aug;58(8):2543-8. doi: 10.1002/art.23696.
PubMed 18668587
Study at a glance
From the registry record, last updated by the sponsor on 5 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Clinical Trial of Imatinib Mesylate(Glivec)in Patients With Moderate to Severe Nephrogenic Systemic Fibrosis
- ClinicalTrials.gov ID
- NCT00981942
- Acronym / sponsor ID
- NSF / 22505 TRE
- Conditions
- Nephrogenic Systemic Fibrosis
- Keywords
- Nephrogenic systemic fibrosis, Imatinib mesylate, Glivec, Gleevec
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- University of AarhusUniversity, hospital or other
- Study start
- Sep 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 22 Sep 2009 (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.
The investigators will study the effect of imatinib mesylate (Glivec) in treatment of moderate to severe nephrogenic systemic fibrosis (NSF).
So far there is no evidence of adequately effective treatment options of NSF. Various treatments have been tried to stop the progressing disease. Corticosteroids, which suppress the early inflammatory stage of the disease, fail to halt disease progression.
Other immunosuppressive agents, photopheresis, and kidney transplantations are reported to be partly beneficial to the patients.
It has not been possible to confirm these findings in further studies because in photopheresis, and kidney transplantation, such effects are generally unreproducible.
Detailed description
NSF is a relatively newly defined fibrosing disease not described before 1997 where the Gadolinium-based contrast agents (GBCAs) were introduced in patients with kidney disease. The association between NSF and GBCA has in many studies shown to be very strong. Until recently, radiologists believed that commercially available GBCAs were safe to use whether the renal function was normal or not. Since the 1980s, >200 million patients have been given these agents. Lately, the occurrence of NSF, a relatively new chronic disorder, has given serious speculations about the safety of these drugs and has questioned their future use. First identified in 1997, but not described until 2000, NSF has been reported only in patients with acute or chronic severe renal insufficiency (with a glomerular filtration rate <30 ml/min/1.73 m2).
Fibrosis in the subcutis means that the skin hardens and loses flexibility. Hard dermal plaque changes often appear on legs, arms and abdomen together with dyspigmentation. As the lesions involve the deep part of the subcutis the muscles are often affected. Involvement of the joints leads to contractures and narrowing of movement. Patients with massive affection of the joints often end up with a zimmer frame or in a wheelchair. The connecting tissue in the inner vital organs may also be affected and NSF can accelerate the death of the patient. The retained gadolinium in lesions of NSF can be found years after administration.
Interestingly, a case report suggests beneficial effects of imatinib mesylate in two patients. Two other independent case reports also show promising results.
Imatinib mesylate inhibits several tyrosine kinases involved in the fibrotic reaction, which is one of the main pathogenetic components of NSF.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age > 18 years
- Diagnosed with NSF
- mRodnan skin score => 20 or
- Rapid progression of the disease defined as a 50% increase in mRodnan skin score in less than 7 weeks or
- Progression of the fibrosis in the inner organs ex. the heart or the lungs, AND
Key exclusion criteria (4 listed)
- Known sensitivity to Imatinib mesylate or to any of its components
- Pregnant or lactating woman
- ALAT > 3 x upper limit of normal
- Severe congestive heart failure (NYHA Class III or IV)
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 |
|---|---|---|
| Imatinib mesylate (Glivec)Also: Glivec, Gleevec400 mg, one tablet daily for 12 or 24 weeks | Drug | – |
Primary outcome
The primary endpoints are skin fibrosis and joint mobility.
Time frame: 16 weeks or 28 weeks
1 secondary outcome
The secondary endpoint is and joint mobility.
Time frame: 16 weeks or 28 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jun 2012.
- Background: PubMed 18668587Kay J, High WA. Imatinib mesylate treatment of nephrogenic systemic fibrosis. Arthritis Rheum. 2008 Aug;58(8):2543-8. doi: 10.1002/art.23696.
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.
Anne B Olesen, MD,PhD principal investigator
Anne Braae Olesen
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Imatinib mesylate (Glivec) in people with Nephrogenic Systemic Fibrosis, run by University of Aarhus at 2 sites in Denmark.
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 6 inclusion and 4 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: finished, as of the sponsor's last update on 5 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Denmark. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The primary endpoints are skin fibrosis and joint mobility. (time frame: 16 weeks or 28 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00981942, which also lists 1 linked publication.
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 5 Jun 2012.