Idiopathic Pulmonary FibrosisPhase 2/3NCT00981747
Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis
A Phase 2/3 study testing Sildenafil, Losartan and Sildenafil and Losartan in people with Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis, run by Alicia Gerke at 1 site in United States.
Trial summary
The purpose of this study is to determine whether combination therapy with sildenafil and losartan can improve function and exercise tolerance in patients with idiopathic pulmonary fibrosis. Read more about this study
- Who is it for?
- Ages 18 to 99 years
- Conditions the study is for
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
- What is being tested?
- Sildenafil, Losartan and Sildenafil and Losartan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2009to Dec 2016
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 99 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-99
- Have not taken any of the study medications in the past 6 weeks
- Diagnosed with idiopathic pulmonary fibrosis
Who cannot join
- FVC<50%, DLco <30% or FEV1/FVC ratio <65%
- Greater amount of emphysema than fibrotic change on chest CT scan
- Acute myocardial infarction within the past 6 months
- Nitrate use
- Contraindications, hypersensitivity, or allergic reaction to any study medication
- Presence of aortic stenosis
Show all 25Show fewer
- Life-threatening arrhythmia within 1 month of evaluation
- Diabetes requiring insulin therapy
- Second-degree or third-degree atrioventricular block on electrocardiogram
- Echocardiographic evidence of severe pulmonary hypertension (>50mmHg) • Severe terminal illness (survival predicted to be less than 1 year)
- Severe congestive heart failure
- Renal impairment (creatinine >2.0 mg/dl)
- Moderate to severe hepatic impairment
- Concurrent treatment with immunosuppressive, cytotoxic, or investigational agents.
- Pregnant or Breastfeeding (Women of childbearing age must use effective form of birth control or abstinence during study participation)
- History of acute exacerbation of IPF
- Current enrollment in another investigational protocol
- Acute or chronic impairment other than dyspnea that limits the patient's ability to perform the six minute walk test
- Current drug or alcohol dependence
- Initiation of pulmonary rehabilitation within 30 days of enrollment. Subjects currently undergoing maintenance pulmonary rehabilitation at study entry will be asked to maintain their levels of rehabilitation for the duration of the trial
- Treatment of pulmonary hypertension with prostaglandins, endothelin-1 antagonists, or any other phosphodiesterase inhibitor within 30 days of enrollment
- Addition or discontinuation of calcium channel blockers, digitalis, diuretics or vasodilators within 30 days of enrollment. Dosage must be stable for 7 days prior to enrollment (except for diuretics)
- Listed for lung transplantation
- Due to drug interactions, all of the following agents will be prohibited: alpha-blockers, endothelin-1 antagonists, and CYP3A4 inhibitors
- Resting oxygen saturation of <92% with greater than 6 liters of supplemental oxygen
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Iowa Hospitals and Clinics
Iowa City, Iowa, 52246
About this study
Official title: A Clinical Treatment Trial Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis
The purpose of this study is to determine whether combination therapy with sildenafil and losartan can improve function and exercise tolerance in patients with idiopathic pulmonary fibrosis.
Read the detailed description
It is currently suspected that the fibrosis in IPF is based upon an abnormal reparative process in the lung. Normally, an insult to the endothelium or epithelium of the lung would trigger an inflammatory process to help repair the site of injury; epithelial and endothelial cells then replicate and repair the tissue damage. In pulmonary fibrosis, alterations in this cascade change the balance of the inflammatory products and reduce the regulatory response which can produce continued inflammation. Fibrosis results from continued deposition of collagen by proliferating fibroblasts and lack of collagen breakdown.
In addition to fibrosis and microvascular destruction, pulmonary hypertension in IPF patients is a significant contributor to morbidity and mortality. The prevalence ranges from 32-85%, suggesting that pulmonary vascular disease is one of several processes that contribute to severity of disease.
We propose use of two therapeutic agents that affect the balance of vasoconstriction and vasodilation to improve basal tone of the vasculature. First, we propose the use of a phosphodiesterase inhibitor. Sildenafil (Viagra, Revatio) is an orally administered vasodilator that prolongs the effect of nitric oxide by inhibiting phosphodiesterase type 5 (PDE-5) which is responsible for degradation of cGMP. Increased cGMP concentration results in pulmonary vasculature relaxation and consequent vasodilation. Second, the use of an angiotensin receptor blocker (ARB) acts to diminish the direct vasoconstrictor effect of angiotensin and endothelin-1 in the vessels. In treatment of systemic hypertension, ARBs have been shown to be associated with a decrease in the amount of circulating endothelin-1 and increase in basal nitric oxide release. They have also been shown to rapidly inhibit the generation of reactive oxygen species by inflammatory cells. We test these interventions in a randomized cross-over trial in IPF patients.
- Conditions
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
- Being tested
- Sildenafil, Losartan, Sildenafil and Losartan, Placebo Oral Tablet
- Medical subject headings
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SildenafilDrug
Also called Viagra, Revatio
Sildenafil 20mg three times per day for 3 months followed by a one month washout prior to next intervention.
LosartanDrug
Also called Cozaar: losartan
Losartan 25mg two times a day for 3 months followed by a one month washout prior to next intervention.
Sildenafil and LosartanDrug
Also called Viagra, Revatio: sildenafil, Cozaar: losartan
Sildenafil 20mg three times per day and Losartan 25mg two times per day followed by a one month washout prior to next intervention.
Placebo Oral TabletDrug
Also called Placebo pill (sugar)
Placebo pill three times per day for 3 months followed by a one month washout prior to next intervention.
| Study group | Role | What they receive |
|---|---|---|
| All study participants | Experimental | Study participants are patients that have been diagnosed with idiopathic pulmonary fibrosis (IPF). Receives: Drug: Sildenafil; Drug: Losartan; Drug: Sildenafil and Losartan; Drug: Placebo Oral Tablet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Six Minute Walk Distance in Meters
Change in 6MWD before and after treatment compared to placebo
Measured: At baseline and three months post each intervention.
Secondary outcomes (2)
Change in Forced Vital Capacity (FVC)
Change in FVC before and after treatment compared to placebo. FVC is a measure of lung size.
Measured: At baseline and three months post each intervention.
Change in Shortness of Breath (SOB) Score
Change in symptoms of SOB as determined by St. Georges Respiratory Questionnaire score. This score ranges from 0 to 100 with a higher score indicating more problems breathing.
Measured: At baseline and three months post each intervention.
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 2016
- Study completionDec 2016
Why it stopped: Funding was withdrawn.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Idiopathic Pulmonary FibrosisStudies of the same condition, open and under way.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Participants will receive sildenafil for three months then losartan for three months, then sildenafil and losartan for three months and then placebo for three months in a random order.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Alicia Gerke
- Sponsor type
- University, hospital or other
- Collaborators
- Pulmonary Fibrosis Foundation
- Responsible party
- Sponsor-investigator, Alicia Gerke, University of Iowa
- Investigators
- Alicia K Gerke, MD, Principal investigator, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00981747
- Sponsor's protocol ID
- 200906736
- Status last verified
- Oct 2018
- First submitted
- 19 Sep 2009
- Last updated
- 13 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Clinical Treatment Trial Targeting Vascular Reactivity in Idiopathic Pulmonary Fibrosis
- ClinicalTrials.gov ID
- NCT00981747
- Acronym / sponsor ID
- 200906736
- Conditions
- Idiopathic Pulmonary Fibrosis, Pulmonary Fibrosis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Funding was withdrawn.
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Alicia GerkeUniversity, hospital or other
- Collaborators
- Pulmonary Fibrosis Foundation
- Study start
- Sep 2009 (actual)
- Primary completion
- Dec 2016 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 22 Sep 2009 (estimated)
- Results
- Posted 13 Nov 2018
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 this study is to determine whether combination therapy with sildenafil and losartan can improve function and exercise tolerance in patients with idiopathic pulmonary fibrosis.
Detailed description
It is currently suspected that the fibrosis in IPF is based upon an abnormal reparative process in the lung. Normally, an insult to the endothelium or epithelium of the lung would trigger an inflammatory process to help repair the site of injury; epithelial and endothelial cells then replicate and repair the tissue damage. In pulmonary fibrosis, alterations in this cascade change the balance of the inflammatory products and reduce the regulatory response which can produce continued inflammation. Fibrosis results from continued deposition of collagen by proliferating fibroblasts and lack of collagen breakdown.
In addition to fibrosis and microvascular destruction, pulmonary hypertension in IPF patients is a significant contributor to morbidity and mortality. The prevalence ranges from 32-85%, suggesting that pulmonary vascular disease is one of several processes that contribute to severity of disease.
We propose use of two therapeutic agents that affect the balance of vasoconstriction and vasodilation to improve basal tone of the vasculature. First, we propose the use of a phosphodiesterase inhibitor. Sildenafil (Viagra, Revatio) is an orally administered vasodilator that prolongs the effect of nitric oxide by inhibiting phosphodiesterase type 5 (PDE-5) which is responsible for degradation of cGMP. Increased cGMP concentration results in pulmonary vasculature relaxation and consequent vasodilation. Second, the use of an angiotensin receptor blocker (ARB) acts to diminish the direct vasoconstrictor effect of angiotensin and endothelin-1 in the vessels. In treatment of systemic hypertension, ARBs have been shown to be associated with a decrease in the amount of circulating endothelin-1 and increase in basal nitric oxide release. They have also been shown to rapidly inhibit the generation of reactive oxygen species by inflammatory cells. We test these interventions in a randomized cross-over trial in IPF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- Double blind (participant, investigator)
- Number of arms
- 1
- Model description
- Participants will receive sildenafil for three months then losartan for three months, then sildenafil and losartan for three months and then placebo for three months in a random order.
| Arm | Type | Receives |
|---|---|---|
| All study participants | Experimental | Drug: Sildenafil, Drug: Losartan, Drug: Sildenafil and Losartan, Drug: Placebo Oral TabletStudy participants are patients that have been diagnosed with idiopathic pulmonary fibrosis (IPF). |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age 18-99
- Have not taken any of the study medications in the past 6 weeks
- Diagnosed with idiopathic pulmonary fibrosis
Key exclusion criteria (25 listed)
- FVC<50%, DLco <30% or FEV1/FVC ratio <65%
- Greater amount of emphysema than fibrotic change on chest CT scan
- Acute myocardial infarction within the past 6 months
- Nitrate use
- Contraindications, hypersensitivity, or allergic reaction to any study medication
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 |
|---|---|---|
| SildenafilAlso: Viagra, RevatioSildenafil 20mg three times per day for 3 months followed by a one month washout prior to next intervention. | Drug | All study participants |
| LosartanAlso: Cozaar: losartanLosartan 25mg two times a day for 3 months followed by a one month washout prior to next intervention. | Drug | All study participants |
| Sildenafil and LosartanAlso: Viagra, Revatio: sildenafil, Cozaar: losartanSildenafil 20mg three times per day and Losartan 25mg two times per day followed by a one month washout prior to next intervention. | Drug | All study participants |
| Placebo Oral TabletAlso: Placebo pill (sugar)Placebo pill three times per day for 3 months followed by a one month washout prior to next intervention. | Drug | All study participants |
Primary outcome
Change in Six Minute Walk Distance in Meters
Time frame: At baseline and three months post each intervention.
Change in 6MWD before and after treatment compared to placebo
2 secondary outcomes
Change in Forced Vital Capacity (FVC)
Time frame: At baseline and three months post each intervention.
Change in Shortness of Breath (SOB) Score
Time frame: At baseline and three months post each intervention.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Alicia K Gerke, MD principal investigator
University of Iowa
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sildenafil, Losartan and Sildenafil and Losartan in people with Idiopathic Pulmonary Fibrosis and Pulmonary Fibrosis, run by Alicia Gerke 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 25 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 13 Nov 2018. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Yes. Results are posted in the registry (first posted 13 Nov 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Change in Six Minute Walk Distance in Meters (time frame: At baseline and three months post each intervention.). 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 13 Nov 2018.