Cystic Fibrosis With Mild to Moderate Lung DiseasePhase 1/2NCT01194232
Sildenafil Trial in Children and Young Adults With CF
A Phase 1/2 study testing Sildenafil in people with Cystic Fibrosis With Mild to Moderate Lung Disease and CMRI of Lung Perfusion, run by Children's Hospital Medical Center, Cincinnati.
Trial summary
Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. Read more about this study
- Who is it for?
- Ages 8 to 21 years
- Conditions the study is for
- Cystic Fibrosis With Mild to Moderate Lung Disease, CMRI of Lung Perfusion, Lung Perfusion
- What is being tested?
- Sildenafil
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Aug 2012to Dec 2012
- Phase
- Phase 1/2
- 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 8 to 21 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Research subjects must meet the following inclusion criteria:
- Age 8 years to age 21 years
- Weight > 20kg
- Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60 mmol/liter or by two identified CFTR mutations on genetic analysis
- Able to perform acceptable and repeatable spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) joint consensus criteria.
- Have valid spirometry data for at least 3 years
Show all 14Show fewer
- Must have mild to moderate lung disease (Mild lung disease will be defined as an FEV1%p of 80-99% predicted. Moderate lung disease will be defined as an FEV1%p of 60-79% predicted.)
- If under the age of 18, the subject must assent to participation in the study, and the subject's parent or guardian must be able to give written informed consent and comply with the requirements of the study protocol
- If 18 years of age or older, the subject must be able to give written parental permission and comply with the requirements of the study protocol
- For female subjects: negative serum pregnancy test and must be willing to use contraception during study participation
- Able to tolerate MRI without sedation
- Subjects who are on alternating monthly on/off cycles of inhaled antibiotics must be willing to be off of inhaled antibiotic therapy for one "on" cycle.
- Must be currently enrolled in CCHMC IRB#: 2008-0926
- Normal Vitamin K status (PT/IND, PIVKA, etc) at screening
Who cannot join
- Research subjects will be excluded from the study based on:
- History of CF-related liver disease with portal hypertension
- Currently smoking cigarettes or other tobacco products
- Use of daytime oxygen supplementation
- Previous organ transplantation
- Unstable or uncontrolled hypertension
Show all 29Show fewer
- Ongoing use of oral corticosteroids
- For female subjects: pregnancy or lactation and unwillingness to use contraception during study participation
- Any hemodynamically significant congenital or acquired cardiac disease or significant cardiomyopathy, hematologic disease (i.e. hemoglobinopathies), or pulmonary disease associated with an increased risk of pulmonary perfusion defects or pulmonary hypertension other than as an outcome of CF
- History of renal and/or hepatic insufficiency, defined as cystatin-C level that exceeds normal range and a previous diagnosis of liver cirrhosis.
- History of uncontrolled asthma defined as oral steroid dependent
- History of hypersensitivity to gadolinium (Magnevist)
- Contraindications specific to MRI including a history of claustrophobia, cardiac pacemaker, or other non-MRI compatible surgical implants (This includes neuro-stimulators containing electrical circuitry, or which generate electrical signals and/or have moving metal parts, and metal orthopedic pins or plates. The research coordinator and/or the MRI technologist will screen all subjects using the standard checklist of medical history and safety questions used by the Radiology Department in routine clinical scans.)
- Daily use of montelukast and ibuprofen
- Use of nitrate medicines or other drugs known to have unsafe interactions with Sildenafil
- Known allergy to Sildenafil
- Inability to comply with study procedures
- History of the following:
- Tinnitus or hearing impairment
- CF exacerbation within the preceding two months
- Ulcer, severe gastritis, or prior GI bleed
- Recurrent epistaxis
- Diabetes or abnormal OGTT (risk of retinal hemorrhage with sildenafil is highest in diabetics)
- Laboratory Exclusion Criteria for research subjects (based on history or blood work before first MRI):
- Positive sputum, epiglottic, or bronchoalveolar lavage culture for Mycobacterium abscessus during the 2 years prior to enrollment
- A positive serum pregnancy test
- Serum creatinine > two times the upper limit of normal for age
- A serum Cystatin C < 60 ml/min/1.73m2
- Vitamin K outside of normal range
About this study
Official title: Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease
Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.
- Conditions
- Cystic Fibrosis With Mild to Moderate Lung Disease, CMRI of Lung Perfusion, Lung Perfusion, Lung Vascularization
- Being tested
- Sildenafil
- Keywords
- Cystic Fibrosis, CF, CMRI, vascularization, perfusion
- Medical subject headings
- Cystic Fibrosis, Neovascularization, Pathologic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose.
| Study group | Role | What they receive |
|---|---|---|
| Sildenafil | Experimental | 15 subjects will receive 8 week course of Sildenafil administered at a dose of 20 mg per dose three times per day. Receives: Drug: Sildenafil |
What is being measured
The primary outcome is the main question the study is designed to answer.
Increase pulmonary perfusion
- Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;
Measured: 8 week visit
Secondary outcomes (1)
Improved lung function
- Improved exercise performance as measured by the following variables:
- Ventilatory equivalent of O2 and CO2 (VEO2 and VECO2)
- Maximum oxygen consumption (VO2 max)
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Sep 2010 (estimated)
- Study startAug 2012
- Primary completionDec 2012
- Study completionDec 2012
Why it stopped: Funding, MedWatch change to study drug
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cystic Fibrosis With Mild to Moderate Lung DiseaseStudies of the same condition, open and under way.
- More trials run by Children's Hospital Medical Center, CincinnatiThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01194232
- Sponsor's protocol ID
- 2010-2067
- Status last verified
- Dec 2012
- First submitted
- 1 Sep 2010
- Last updated
- 11 Dec 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Study of Sildenafil in Children and Young Adults With Mild to Moderate Cystic Fibrosis Lung Disease
- ClinicalTrials.gov ID
- NCT01194232
- Acronym / sponsor ID
- 2010-2067
- Conditions
- Cystic Fibrosis With Mild to Moderate Lung Disease, CMRI of Lung Perfusion, Lung Perfusion, Lung Vascularization
- Keywords
- Cystic Fibrosis, CF, CMRI, vascularization, perfusion
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Funding, MedWatch change to study drug
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Study start
- Aug 2012
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2012 (actual)
- First posted
- 2 Sep 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.
Cystic Fibrosis (CF), the most common inherited disease in Caucasians, is characterized by chronic pulmonary inflammation and progressive loss of gas exchange units that eventually results in respiratory failure. There is strong evidence that, in CF, abnormally low perfusion carries a high risk of death independent from the presence of pulmonary hypertension. However, the evolution of pulmonary vascular disease in CF and how it might contribute to the rate of decline in lung function is not known. Our knowledge remains limited to the results of old observational studies which concluded that the major causes of pulmonary vascular remodeling and hypertension in CF are hypoxic respiratory failure and destruction of lung tissue. Our recent data obtained by state-of-the-art Magnetic Resonance Imaging (MRI) of the pulmonary circulation, challenges the existing paradigm. We demonstrate that in the absence of hypoxia, significant changes in pulmonary perfusion and in surrogate measures of vascular resistance as well as in collateral blood flow begin early in the course of CF. Newly developed therapeutics have altered dramatically the course of patients suffering from pulmonary vascular disease. Through this 8 week trial, we will examine by Magnetic Resonance Imaging the effect of Sildenafil on pulmonary perfusion and systemic vascularization of the lungs in subjects with mild to moderate disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sildenafil | Experimental | Drug: Sildenafil15 subjects will receive 8 week course of Sildenafil administered at a dose of 20 mg per dose three times per day. |
Who may qualify
- Ages
- 8 to 21 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (14 listed)
- Age 8 years to age 21 years
- Weight > 20kg
- Diagnosis of cystic fibrosis confirmed by a prior sweat chloride evaluation of > 60 mmol/liter or by two identified CFTR mutations on genetic analysis
- Able to perform acceptable and repeatable spirometry per American Thoracic Society/European Respiratory Society (ATS/ERS) joint consensus criteria.
- Have valid spirometry data for at least 3 years
Key exclusion criteria (29 listed)
- History of CF-related liver disease with portal hypertension
- Currently smoking cigarettes or other tobacco products
- Use of daytime oxygen supplementation
- Previous organ transplantation
- Unstable or uncontrolled hypertension
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 |
|---|---|---|
| Sildenafil8 week course of Sildenafil administered at a dose of 1 mg / Kg three times a day with a maximum dose of 20 mg per dose. | Drug | Sildenafil |
Primary outcome
Increase pulmonary perfusion
Time frame: 8 week visit
• Increase of pulmonary perfusion by a minimum of 15% as measured by gadolinium contrast MRI with segmental perfusion and scored on a continuous scale;
1 secondary outcome
Improved lung function
Time frame: 8 weeks
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Dec 2012.
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.
The record lists no contact. Use the official record to reach the sponsor.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Sildenafil in people with Cystic Fibrosis With Mild to Moderate Lung Disease and CMRI of Lung Perfusion, run by Children's Hospital Medical Center, Cincinnati.
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 14 inclusion and 29 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: withdrawn, as of the sponsor's last update on 11 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
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 combined 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.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 withdrawn before enrolling participants, so there are no results.
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?
Increase pulmonary perfusion (time frame: 8 week visit). 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 Dec 2012.