PAHNCT01092897
Pulmonary Hypertension and Imatinib
An observational study of PAH, run by The Cleveland Clinic at 8 sites in United States.
Trial summary
The purpose of the study is to determine whether circulating molecular and cellular biomarkers are predictive of imatinib effect on pulmonary artery hypertension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- PAH
- How many people
- 130 participants
- Where
- 8 sitesUnited States
- Study dates
- Mar 2010to Dec 2012
- Phase
- Observational
- 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
Study population: Patients diagnosed with PAH that are enrolled in the Imatinib clinical trial.
Who may be able to join
- from Imatinib Trial
- Male or Female 18 years or older
- A current diagnosis or Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD, or PDA), or PAH associated with diet therapies or other drugs
- A PVR>1000dynes.sec.cm-5(as assess by RHC at screening or in the 2 months preceding the screening visit despite treatment with two or more specific PAH therapies, including endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5), or inhaled, intravenous or oral prostacyclin analogues for ≥3 months. On stable background therapy doses for ≥ 30 days except for warfarin (≥30 days but doses can vary even within the mouth before enrollment)
- WHO Functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies must be an inhaled, intravenous or oral prostacyclin analogue, unless the subject has been shown to be intolerant of prostacyclin analogues.
- 6MWD≥150meters and ≥450meters at screening. Distances of two consecutive 6MWTs should be within 15% of one another.
- Ability to provide written informed consent
Who cannot join
- Women of childbearing potential who are not practicing birth control methods.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of positive hCG laboratory test (> 5 mIU/MI)
- Have previously received treatment with imatinib
- In treatment with chronic nitric oxide therapy
- Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, thorax or diaphragm or bronchial asthma associated with chronic hypoxia that may contribute to severity of PAH
- With a pulmonary capillary wedge pressure >15 mm Hg to rule out PAH secondary to left ventricular dysfunction
Show all 38Show fewer
- With a diagnosis of pulmonary artery or vein stenosis
- With other diagnosis of PAH in WHO Diagnostic Group 1 re excluded including congenital systemic to pulmonary shunts (large, small that not surgically repaired, portal hypertension, HIV infection, glycogen storage disease, Gaucher's disease, hereditary hemorrhagic telangiectasia, hemoglobinopthaies, myeloproliferative disorders)
- With a diagnosis of PAH associated with: venous hypertension (WHO Diagnostic Group II), hypoxia (WHO Diagnostic Group III), chronic pulmonary thromboembolic disease (WHO Diagnostic Group IV) or other miscellaneous causes (WHO Diagnostic Class V, which includes sarcoidosis, histiocytosis X, lympangiomatosis, compression of pulmonary vessels).
- With deficient thrombocyte function, thrombocytopenia >50x109/L(50x103/µL)
- With a history of acute heart failure or chronic left sided heart failure
- With uncontrolled systemic arterial hypertension, systolic >160mmHg or diastolic >90mmHg
- With hemoglobin <100g/L (10 g/dl)
- With deficiencies of blood coagulation, inherited or acquired blood disorders, factor XII, factor XIII; decreased generation of coagulation factors due to acute or chronic liver diseases, efficient coagulation due to auto-antibodies against coagulation factors such as in lupus anticoagulant
- With disseminated intravascular coagulation (DIC)
- With evidence of major bleeding or intracranial hemorrhage
- With a history of latent bleeding risk such as diabetic retinopathy, gastrointestinal bleeding due to gastric or duodenal ulcers, or colitis ulcerosa
- With a history of moderate or greater hepatic insufficiency transaminase levels >4times the upper limit or normal or a bilirubin >2times the upper limit of normal
- With a history of renal insufficiency (serum creatinine >200µmol/1or 2.6mg/dl)
- Previous therapeutic radiation of lungs mediastinum
- With a history of sickle cell anemia
- With a QTcF>450msec for males and >470 msec for females at screening
- With a history of ventricular tachycardia, ventricular fibrillation or ventricular flutter
- Having syncope in the 3 months prior to the screening visit
- With a history of Torsades de Pointes
- With a history of long QT syndrome
- Having undergone atrial septostomy in the 3 months prior to screening visit
- Having undergone radiofrequency catheter ablation for atrial or sinus arrhythmias in the 3 months prior to screening visit
- With an advanced, sever, or unstable disease of any type that may interfere with the primary and secondary endpoint evaluations
- With a history of immunodeficiency diseases, including HIV
- With a known hypersensitivity to QTI571 or drugs similar to the study drug
- With a disability that may prevent the patient from competing all study requirements and in particular, interfere with the 6MWT assessment
- With a life expectancy of 6months or less
- Having used other investigational drugs at the time of enrollment, within 30 days or 5 half-lives of enrollment, whichever is longer
- With a history of malignancy of any organ system (other than localized basal cell carcinoma of the skin), treated or untreated, within the past 5 years, regardless of whether there is evidence of local recurrence or metastases.
- With a diagnosis of Hepatitis B or C
- With a history of alcohol abuse within 6 months of screening
- With a history of illicit drug abuse within 6 months of screening
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Colorado Denver
Aurora, Colorado
Johns Hopkins
Baltimore, Maryland, 21205
Tufts Medical Center
Boston, Massachusetts
Cleveland Clinic
Cleveland, Ohio, 44195
UT Southwestern Medical Center of Dallas
Dallas, Texas, 75390-8550
University of Pittsburgh
Pittsburgh, Pennsylvania
Mayo Clinic
Rochester, Minnesota
Cleveland Clinic Florida
Weston, Florida
About this study
Official title: Biomarkers in Pulmonary Arterial Hypertension Treated With Imatinib
The purpose of the study is to determine whether circulating molecular and cellular biomarkers are predictive of imatinib effect on pulmonary artery hypertension.
Read the detailed description
We hypothesize that bone marrow progenitor cells are mobilized into the circulation in PAH, home to the lungs and differentiate into mast cells, which promote vascular remodeling and vasoconstriction through release of renin and chymase. As a corollary to this, we hypothesize that anti cKit tyrosine kinase inhibitor (TKI), imatinib, provides clinical benefit to patients through inhibition of mast cell progenitor proliferation, mobilization and differentiation. To test this, we will determine if mast cell progenitors and mast cell biomarkers are related to imatinib clinical response. This will be an ancillary study, part of a placebo-controlled, double-blind multi center clinical trial of imatinib in pulmonary arterial hypertension.
- Conditions
- PAH
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Subjects with PAH treated with Imatinib | Not described |
What is being measured
The primary outcome is the main question the study is designed to answer.
Measuring circulating biomarkers of imatinib affect
Measured: within one year of the end of the study
Secondary outcomes (1)
Evaluate effect of imatinib on the activation of mast cells
Measured: within one year of the end of the study
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionDec 2012
- Study completionDec 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for PAHStudies of the same condition, open and under way.
- More trials run by The Cleveland ClinicThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Cleveland Clinic
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kewal Asosingh, Ph.D, The Cleveland Clinic
- Investigators
- Kewal Asosingh, M.S., Ph.D, Principal investigator, The Cleveland Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01092897
- Sponsor's protocol ID
- 09-782
- Status last verified
- Feb 2014
- First submitted
- 24 Mar 2010
- Last updated
- 4 Feb 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med. 2006 Jul 18;145(2):152-3. doi: 10.7326/0003-4819-145-2-200607180-00020. No abstract available.
PubMed 16847299Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005 Oct;115(10):2811-21. doi: 10.1172/JCI24838.
PubMed 16200212Dentelli P, Rosso A, Balsamo A, Colmenares Benedetto S, Zeoli A, Pegoraro M, Camussi G, Pegoraro L, Brizzi MF. C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood. 2007 May 15;109(10):4264-71. doi: 10.1182/blood-2006-06-029603. Epub 2007 Feb 8.
PubMed 17289809Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6. doi: 10.1136/jcp.44.12.1003.
PubMed 1791199Hamada H, Terai M, Kimura H, Hirano K, Oana S, Niimi H. Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med. 1999 Oct;160(4):1303-8. doi: 10.1164/ajrccm.160.4.9810058.
PubMed 10508822
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biomarkers in Pulmonary Arterial Hypertension Treated With Imatinib
- ClinicalTrials.gov ID
- NCT01092897
- Acronym / sponsor ID
- 09-782
- Conditions
- PAH
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- The Cleveland ClinicUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 25 Mar 2010 (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 purpose of the study is to determine whether circulating molecular and cellular biomarkers are predictive of imatinib effect on pulmonary artery hypertension.
Detailed description
We hypothesize that bone marrow progenitor cells are mobilized into the circulation in PAH, home to the lungs and differentiate into mast cells, which promote vascular remodeling and vasoconstriction through release of renin and chymase. As a corollary to this, we hypothesize that anti cKit tyrosine kinase inhibitor (TKI), imatinib, provides clinical benefit to patients through inhibition of mast cell progenitor proliferation, mobilization and differentiation. To test this, we will determine if mast cell progenitors and mast cell biomarkers are related to imatinib clinical response. This will be an ancillary study, part of a placebo-controlled, double-blind multi center clinical trial of imatinib in pulmonary arterial hypertension.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Subjects with PAH treated with Imatinib | – | – |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients diagnosed with PAH that are enrolled in the Imatinib clinical trial.
Key inclusion criteria (7 listed)
- from Imatinib Trial
- Male or Female 18 years or older
- A current diagnosis or Pulmonary Arterial Hypertension according to the Dana Point 2008 Meeting: WHO Diagnostic Group I, idiopathic or heritable (familial or sporadic) PAH, PAH associated with collagen vascular disease including systemic sclerosis, rheumatoid arthritis, mixed connective tissue diseases, and overlap syndrome. PAH following one year repair of congenital heart defect (ASD, VSD, or PDA), or PAH associated with diet therapies or other drugs
- A PVR>1000dynes.sec.cm-5(as assess by RHC at screening or in the 2 months preceding the screening visit despite treatment with two or more specific PAH therapies, including endothelin receptor antagonists (ERA), phosphodiesterase 5 inhibitors (PDE5), or inhaled, intravenous or oral prostacyclin analogues for ≥3 months. On stable background therapy doses for ≥ 30 days except for warfarin (≥30 days but doses can vary even within the mouth before enrollment)
- WHO Functional Class II-IV. For WHO Functional Class IV, one of the 2 or more specific PAH therapies must be an inhaled, intravenous or oral prostacyclin analogue, unless the subject has been shown to be intolerant of prostacyclin analogues.
Key exclusion criteria (38 listed)
- Women of childbearing potential who are not practicing birth control methods.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of positive hCG laboratory test (> 5 mIU/MI)
- Have previously received treatment with imatinib
- In treatment with chronic nitric oxide therapy
- Pre-existing lung disease including parasitic diseases affecting lungs, congenital abnormalities of the lungs, thorax or diaphragm or bronchial asthma associated with chronic hypoxia that may contribute to severity of PAH
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Measuring circulating biomarkers of imatinib affect
Time frame: within one year of the end of the study
1 secondary outcome
Evaluate effect of imatinib on the activation of mast cells
Time frame: within one year of the end of the study
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 4 Feb 2014.
- Background: PubMed 16847299Patterson KC, Weissmann A, Ahmadi T, Farber HW. Imatinib mesylate in the treatment of refractory idiopathic pulmonary arterial hypertension. Ann Intern Med. 2006 Jul 18;145(2):152-3. doi: 10.7326/0003-4819-145-2-200607180-00020. No abstract available.
- Background: PubMed 16200212Schermuly RT, Dony E, Ghofrani HA, Pullamsetti S, Savai R, Roth M, Sydykov A, Lai YJ, Weissmann N, Seeger W, Grimminger F. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest. 2005 Oct;115(10):2811-21. doi: 10.1172/JCI24838.
- Background: PubMed 17289809Dentelli P, Rosso A, Balsamo A, Colmenares Benedetto S, Zeoli A, Pegoraro M, Camussi G, Pegoraro L, Brizzi MF. C-KIT, by interacting with the membrane-bound ligand, recruits endothelial progenitor cells to inflamed endothelium. Blood. 2007 May 15;109(10):4264-71. doi: 10.1182/blood-2006-06-029603. Epub 2007 Feb 8.
- Background: PubMed 1791199Heath D, Yacoub M. Lung mast cells in plexogenic pulmonary arteriopathy. J Clin Pathol. 1991 Dec;44(12):1003-6. doi: 10.1136/jcp.44.12.1003.
- Background: PubMed 10508822Hamada H, Terai M, Kimura H, Hirano K, Oana S, Niimi H. Increased expression of mast cell chymase in the lungs of patients with congenital heart disease associated with early pulmonary vascular disease. Am J Respir Crit Care Med. 1999 Oct;160(4):1303-8. doi: 10.1164/ajrccm.160.4.9810058.
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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.
Kewal Asosingh, M.S., Ph.D principal investigator
The Cleveland Clinic
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of PAH, run by The Cleveland Clinic at 8 sites 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 7 inclusion and 38 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 4 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
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?
Measuring circulating biomarkers of imatinib affect (time frame: within one year of the end of the study). 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 NCT01092897, which also lists 5 linked publications.
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 4 Feb 2014.