Cystic FibrosisPhase 2NCT00405665
The Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
A Phase 2 study testing L-arginine in people with Cystic Fibrosis, run by The Hospital for Sick Children at 2 sites in Canada.
Trial summary
The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients. Read more about this study
- Who is it for?
- Ages 14 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- L-arginine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 2 sitesCanada
- Study dates
- Nov 2006to Jun 2009
- Phase
- Phase 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 14 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration > 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
- 14 years of age and older at enrollment
- Clinically stable at enrollment
- Ability to comply with medication use, study visits and study procedures
- FEV1 % predicted > 40% < 80 % as calculated by reference equations
Who cannot join
- Respiratory culture positive for: B. cepacia complex within past year or at screening
- Use of systemic corticosteroids within 30 days of screening
- Use of intravenous antibiotics or oral quinolones within 14 days of screening
- History of biliary cirrhosis, portal hypertension, or splenomegaly
- Other major organ dysfunction
- History of lung transplantation or currently on lung transplant list
Show all 14Show fewer
- Supplemental oxygen therapy
- Oxygen saturation < 95 % on room air
- Positive pregnancy test at screening
- Investigational drug use within 30 days of screening
- History of alcohol, illicit drug or medication abuse within 1 year of screening
- Acute respiratory symptoms
- Inability to take any form of bronchodilator
- Wheezing at the time of study
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Michael's Hospital
Toronto, Ontario, M5B 1W8
The Hospital for Sick Children
Toronto, Ontario, M5G 1X8
About this study
Official title: Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
The objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.
Read the detailed description
Despite the inflammatory nature of lung disease in CF, nitric oxide (NO) formation as well as the expression of NOS2 has been found to be decreased in CF airways. While the reasons for impaired airway NO formation remain incompletely understood, there is evidence that low NO formation contributes to lung pathophysiology in CF. Constitutive endogenous formation of Nitric oxide (NO) in airways is thought to play a role in neurotransmission, smooth muscle relaxation and bronchodilation. Previous animal experiments have shown that the addition of L-arginine, the precursor of enzymatic NO formation, resulted in a significantly greater relaxation of tracheas. There is also evidence that a single dose of inhaled L-arginine improves pulmonary function in CF. In this study we will assess the effect of L-arginine inhalation on lung function, nitric oxide formation, airway inflammation and bacterial infection in CF patients.
- Conditions
- Cystic Fibrosis
- Being tested
- L-arginine
- Keywords
- Cystic Fibrosis, L-Arginine, Pediatrics, pulmonary function
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
L-arginineDrug
Group 1 will receive the active treatment followed by the inactive treatment. The active treatment phase will consist of L-arginine 250 mg/ml dispensed in 2.2 ml vials, from which the patient will take 2ml (500mg) and dilute with 3ml of sterile water to give 5ml of a 100mg/ml solution. Dosing in the inactive treatment phase will consist of a placebo of similar osmolarity and appearance will be formulated and dosed in a similar fashion. It will consist of 2.2ml vials of 1110mmol/L hypertonic saline. Again, the patient will take 2ml and dilute with 3ml of sterile water to give a 445mmol/L solution which has similar tonicity (10%) to the L-arginine. Both treatment phases will be administered by inhalation with a PARI eFLOW device.
L-arginineDrug
Group 2 will receive the inactive treatment followed by the active treatment.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: L-arginine |
| 2 | Experimental | Not described Receives: Drug: L-arginine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in FEV1 (in liters) from baseline
Measured: At the end of the 14 day treatment period
Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath
Measured: 70 weeks
Secondary outcomes (4)
Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period.
Measured: Will be measured at the end of the 14 day treatment period
Change in exhaled nitric oxide (FeNO)
Measured: 70 days
Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum).
Measured: Will me measured at the end of the 14 day treatment period
Changes in sputum concentrations of L-arginine metabolites
Measured: 70 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Nov 2006 (estimated)
- Study startNov 2006
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felix Ratjen, The Hospital for Sick Children
- Investigators
- Felix Ratjen, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00405665
- Sponsor's protocol ID
- 1000009282
- Status last verified
- Aug 2013
- First submitted
- 28 Nov 2006
- Last updated
- 2 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.
PubMed 37319354Grasemann H, Tullis E, Ratjen F. A randomized controlled trial of inhaled L-arginine in patients with cystic fibrosis. J Cyst Fibros. 2013 Sep;12(5):468-74. doi: 10.1016/j.jcf.2012.12.008. Epub 2013 Jan 14.
PubMed 23333044
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of the Short Term Safety and Efficacy of Inhaled L-arginine in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00405665
- Acronym / sponsor ID
- 1000009282
- Conditions
- Cystic Fibrosis
- Keywords
- Cystic Fibrosis, L-Arginine, Pediatrics, pulmonary function
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Nov 2006
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 30 Nov 2006 (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 objective of this trial is to determine the safety and effect on pulmonary function of 14 days of inhaled L-arginine versus placebo administered over a period of 14 days in a cohort of CF patients.
Detailed description
Despite the inflammatory nature of lung disease in CF, nitric oxide (NO) formation as well as the expression of NOS2 has been found to be decreased in CF airways. While the reasons for impaired airway NO formation remain incompletely understood, there is evidence that low NO formation contributes to lung pathophysiology in CF. Constitutive endogenous formation of Nitric oxide (NO) in airways is thought to play a role in neurotransmission, smooth muscle relaxation and bronchodilation. Previous animal experiments have shown that the addition of L-arginine, the precursor of enzymatic NO formation, resulted in a significantly greater relaxation of tracheas. There is also evidence that a single dose of inhaled L-arginine improves pulmonary function in CF. In this study we will assess the effect of L-arginine inhalation on lung function, nitric oxide formation, airway inflammation and bacterial infection in CF patients.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: L-arginine |
| 2 | Experimental | Drug: L-arginine |
Who may qualify
- Ages
- 14 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Diagnosis of CF as defined by two or more clinical features of CF and a documented sweat chloride concentration > 60 mEq/L and/or two well characterized disease causing CFTR gene mutations
- 14 years of age and older at enrollment
- Clinically stable at enrollment
- Ability to comply with medication use, study visits and study procedures
- FEV1 % predicted > 40% < 80 % as calculated by reference equations
Key exclusion criteria (14 listed)
- Respiratory culture positive for: B. cepacia complex within past year or at screening
- Use of systemic corticosteroids within 30 days of screening
- Use of intravenous antibiotics or oral quinolones within 14 days of screening
- History of biliary cirrhosis, portal hypertension, or splenomegaly
- Other major organ dysfunction
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 |
|---|---|---|
| L-arginineGroup 1 will receive the active treatment followed by the inactive treatment. The active treatment phase will consist of L-arginine 250 mg/ml dispensed in 2.2 ml vials, from which the patient will take 2ml (500mg) and dilute with 3ml of sterile water to give 5ml of a 100mg/ml solution. Dosing in the inactive treatment phase will consist of a placebo of similar osmolarity and appearance will be formulated and dosed in a similar fashion. It will consist of 2.2ml vials of 1110mmol/L hypertonic saline. Again, the patient will take 2ml and dilute with 3ml of sterile water to give a 445mmol/L solution which has similar tonicity (10%) to the L-arginine. Both treatment phases will be administered by inhalation with a PARI eFLOW device. | Drug | 1 |
| L-arginineGroup 2 will receive the inactive treatment followed by the active treatment. | Drug | 2 |
Primary outcome
Change in FEV1 (in liters) from baseline
Time frame: At the end of the 14 day treatment period
Adverse events such as gastrointestinal complaints, wheezing, hepatitis or shortness of breath
Time frame: 70 weeks
4 secondary outcomes
Change in FVC and change in FEV25-75 from baseline to completion of the 2 week treatment period.
Time frame: Will be measured at the end of the 14 day treatment period
Change in exhaled nitric oxide (FeNO)
Time frame: 70 days
Changes in inflammatory markers in sputum from baseline including neutrophils (sputum), neutrophil elastase (sputum) and interleukin (IL)-8 concentrations (sputum).
Time frame: Will me measured at the end of the 14 day treatment period
Changes in sputum concentrations of L-arginine metabolites
Time frame: 70 days
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 2 Sep 2013.
- Derived from this study: PubMed 37319354Wark P, McDonald VM, Smith S. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2023 Jun 14;6(6):CD001506. doi: 10.1002/14651858.CD001506.pub5.
- Derived from this study: PubMed 23333044Grasemann H, Tullis E, Ratjen F. A randomized controlled trial of inhaled L-arginine in patients with cystic fibrosis. J Cyst Fibros. 2013 Sep;12(5):468-74. doi: 10.1016/j.jcf.2012.12.008. Epub 2013 Jan 14.
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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.
Felix Ratjen, MD principal investigator
The Hospital for Sick Children, Toronto Canada
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing L-arginine in people with Cystic Fibrosis, run by The Hospital for Sick Children at 2 sites in Canada.
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 5 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: finished, as of the sponsor's last update on 2 Sep 2013. 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 Canada. 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 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 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?
Change in FEV1 (in liters) from baseline (time frame: At the end of the 14 day treatment period). 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?
On the ClinicalTrials.gov record for NCT00405665, which also lists 2 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 2 Sep 2013.