BronchiectasisEarly Phase 1NCT04090294
Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis
A Early Phase 1 study testing Roflumilast in people with Bronchiectasis, run by Assiut University.
Trial summary
Aim of the work Assessment of early outcome of using Roflumilast in patients with bronchiectasis regarding: Severity of symptoms Frequency of exacerbations Change in pulmonary function Systemic inflammation Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Bronchiectasis
- What is being tested?
- Roflumilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- No sites listed yet
- Study dates
- 1 Oct 2019to Nov 2020
- Phase
- Early Phase 1
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18 years or above, male or female.
- Non / Ex-smokers.
- Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan.
- Significant sputum production (≥ 10 ml per day).
Who cannot join
- Non-stable patients who need ICU admission /mechanical ventilation.
- Active smokers.
- Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min).
- Known psychiatric illness
- Concomitant use of strong cytochrome P450 inducers (e.g. rifampicin)
- Patients who are hypersensitive to roflumilast.
- Pregnant or lactating women
Trial locations and contacts
No sites are listed yet.
About this study
Aim of the work
Assessment of early outcome of using Roflumilast in patients with bronchiectasis regarding:
- Severity of symptoms
- Frequency of exacerbations
- Change in pulmonary function
- Systemic inflammation
Read the detailed description
Bronchiectasis is defined by the presence of permanent and abnormal dilation of the bronchi. This usually occurs in the context of chronic airway infection causing inflammation. The main clinical manifestation is a productive cough. Bronchiectasis is currently nearly always diagnosed using high-resolution computed tomography (HRCT) scanning. The main diagnostic features are: 1) internal diameter of a bronchus is wider than its adjacent pulmonary artery; 2) failure of the bronchi to taper; and 3) visualization of bronchi in the outer 1-2 cm of the lung fields.
- From a series of benzamide derivatives, roflumilast (3-cyclo-propylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) was identified as a potent and selective PDE4 inhibitor. It inhibits PDE4 activity from human neutrophils. PDE4 inhibitors were demonstrated to inhibit inflammatory cytokine and mediator release from inflammatory cells. In addition, it inhibits neutrophil chemotaxis or migratory activity. Lastly, PDE4 inhibitor promotes apoptosis of these cells .
- Studies have demonstrated the efficacy of roflumilast in patients with both asthma and COPD, where roflumilast improved lung function and reduced exacerbation rates.
- Bronchiectasis is a chronic destructive lung disease, which is characterised by persistent bacterial colonization, bronchial inflammation, reduced mucociliaryclearance, and in some patients progressive tissue damage. There is evidence of an associated influx of neutrophils into the lungs of these patients , resulting in the expectoration of large volumes of purulent sputum containing neutrophils and their products, so In patients with bronchiectasis, there is also neutrophilic inflammation as in COPD.
- The PDE4 inhibitor, roflumilast, was evaluated in short term clinical trial of non-cystic fibrosis bronchiectasis. It has been shown symptomatic improvement from baseline Park J. found that 16 weeks Roflumilast treatment in patients with non cystic fibrosis bronchiectasis significantly reduce CAT score and improve the symptoms of non-CF bronchiectasis.
- Conditions
- Bronchiectasis
- Being tested
- Roflumilast
- Medical subject headings
- Bronchiectasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoflumilastDrug
Also called phosphodiestrase 4 inhibitor (PDE4)
Roflumilast is a phosphodiesterase (PDE) type 4 inhibitor will be prescribed for three month for the study group. the patients will then be assessed for improvement regarding exacerbation frequency , performance and pulmonary function test.
patients will receive Roflumilast 500 Mcg. Tablet once daily for three months
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast -non roflumilast | Experimental | 35 patients will receive Roflumilast for three months and improvement regarding dyspnea scales , Pulmonary function Test , Six minutes walking test and bronchectasis severity index (FACED) score pre and post therapy will be assessed.
patients will receive Roflumilast 500 Mcg. Tablet Once daily for Three months and then base line assessment will be repeated to evaluate improvement. Receives: Drug: Roflumilast |
What is being measured
The primary outcome is the main question the study is designed to answer.
Assessment of efficacy of Roflumlilast regarding control of patients with non cystic fibrosis bronchiectasis
Assessment of efficacy of Roflumilast on severity of symptoms in patients with bronchiectasis. Frequency of Exacerbation in the three months assessment and need of hospitalization will be the main parameter for efficacy of the new treatment described as number/ 3 months
Measured: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumlilast in change of performance in patients with non cystic fibrosis bronchiectasis
Assessment of efficacy of roflumilast on change dyspnea scale namely mMRCP evaluated at the start of the study and after 1 month and 3 months
Measured: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumlilast on change in Pulmonary function in patients with non cystic fibrosis bronchiectasis
Assessment of efficacy of roflumilast on change in pulmonary function test in patients with bronchiectasis regarding : change in FEV1 by liter per second
Measured: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumlilast on change of symptoms in patients with non cystic fibrosis bronchiectasis
Assessment of efficacy of roflumlilast on severity of symptoms in patients with bronchiactasis evaluated by bronchectasis severity index (FACED) score.
Measured: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficancy of roflumlilast on change in systemic inflammation in patients with non cystic fibrosis bronchiectasis
Assessment of efficacy of roflumlilast on systemic inflammation in patients with bronchiectasis regarding CRP by mg per L
Measured: 3months . outcomes will be evaluated after 1 month and at the end of the study (3 months).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2019
- Study start1 Oct 2019 (estimated)
- Primary completionSep 2020 (estimated)
- Study completionNov 2020 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for BronchiectasisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe 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
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- 35 patients will receive roflumilast for three months and improvement regarding performance , frequency of exacerbation and pulmonary function test will be assessed.
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Maha Ahmed Abd El-Gawad Mohamed Okash, Assiut University
- Investigators
- Ahmad Shaddad, Lecturer, Principal investigator, Assuit University - Assuit - Egypt
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04090294
- Sponsor's protocol ID
- Roflumilast in bronchiectasis
- Status last verified
- Sep 2019
- First submitted
- 21 Aug 2019
- Last updated
- 3 Oct 2019
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: the investigator group is welling to share all Data after finishing the study
Publications
Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol. 2010 May;87(5):895-904. doi: 10.1189/jlb.0809540. Epub 2010 Jan 26.
PubMed 20103769Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.
PubMed 11986413Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. doi: 10.1136/thx.2006.075937. Epub 2007 Jun 15.
PubMed 17573446van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbroker D, Bardin PG. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions. J Allergy Clin Immunol. 2005 Aug;116(2):292-8. doi: 10.1016/j.jaci.2005.04.023.
PubMed 16083782
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of Early Outcomes of Roflumilast in Patients With Non Cystic Fibrosis Bronchiectasis
- ClinicalTrials.gov ID
- NCT04090294
- Acronym / sponsor ID
- Roflumilast in bronchiectasis
- Conditions
- Bronchiectasis
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Oct 2019 (estimated)
- Primary completion
- Sep 2020 (estimated)
- Study completion
- Nov 2020 (estimated)
- First posted
- 16 Sep 2019 (actual)
- 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.
Aim of the work
Assessment of early outcome of using Roflumilast in patients with bronchiectasis regarding:
- Severity of symptoms
- Frequency of exacerbations
- Change in pulmonary function
- Systemic inflammation
Detailed description
Bronchiectasis is defined by the presence of permanent and abnormal dilation of the bronchi. This usually occurs in the context of chronic airway infection causing inflammation. The main clinical manifestation is a productive cough. Bronchiectasis is currently nearly always diagnosed using high-resolution computed tomography (HRCT) scanning. The main diagnostic features are: 1) internal diameter of a bronchus is wider than its adjacent pulmonary artery; 2) failure of the bronchi to taper; and 3) visualization of bronchi in the outer 1-2 cm of the lung fields.
- From a series of benzamide derivatives, roflumilast (3-cyclo-propylmethoxy-4-difluoromethoxy-N-[3,5-di-chloropyrid-4-yl]-benzamide) was identified as a potent and selective PDE4 inhibitor. It inhibits PDE4 activity from human neutrophils. PDE4 inhibitors were demonstrated to inhibit inflammatory cytokine and mediator release from inflammatory cells. In addition, it inhibits neutrophil chemotaxis or migratory activity. Lastly, PDE4 inhibitor promotes apoptosis of these cells .
- Studies have demonstrated the efficacy of roflumilast in patients with both asthma and COPD, where roflumilast improved lung function and reduced exacerbation rates.
- Bronchiectasis is a chronic destructive lung disease, which is characterised by persistent bacterial colonization, bronchial inflammation, reduced mucociliaryclearance, and in some patients progressive tissue damage. There is evidence of an associated influx of neutrophils into the lungs of these patients , resulting in the expectoration of large volumes of purulent sputum containing neutrophils and their products, so In patients with bronchiectasis, there is also neutrophilic inflammation as in COPD.
- The PDE4 inhibitor, roflumilast, was evaluated in short term clinical trial of non-cystic fibrosis bronchiectasis. It has been shown symptomatic improvement from baseline Park J. found that 16 weeks Roflumilast treatment in patients with non cystic fibrosis bronchiectasis significantly reduce CAT score and improve the symptoms of non-CF bronchiectasis.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- 35 patients will receive roflumilast for three months and improvement regarding performance , frequency of exacerbation and pulmonary function test will be assessed.
| Arm | Type | Receives |
|---|---|---|
| Roflumilast -non roflumilast | Experimental | Drug: Roflumilast35 patients will receive Roflumilast for three months and improvement regarding dyspnea scales , Pulmonary function Test , Six minutes walking test and bronchectasis severity index (FACED) score pre and post therapy will be assessed. patients will receive Roflumilast 500 Mcg. Tablet Once daily for Three months and then base line assessment will be repeated to evaluate improvement. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Aged 18 years or above, male or female.
- Non / Ex-smokers.
- Confirmed diagnosis of bronchiectasis based on high-resolution computed tomography scan.
- Significant sputum production (≥ 10 ml per day).
Key exclusion criteria (7 listed)
- Non-stable patients who need ICU admission /mechanical ventilation.
- Active smokers.
- Moderate to severe liver impairment (Child-Pugh B or C) and/or sever renal impairment (c. clearance less than 30ml/min).
- Known psychiatric illness
- Concomitant use of strong cytochrome P450 inducers (e.g. rifampicin)
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 |
|---|---|---|
| RoflumilastAlso: phosphodiestrase 4 inhibitor (PDE4)Roflumilast is a phosphodiesterase (PDE) type 4 inhibitor will be prescribed for three month for the study group. the patients will then be assessed for improvement regarding exacerbation frequency , performance and pulmonary function test. patients will receive Roflumilast 500 Mcg. Tablet once daily for three months | Drug | Roflumilast -non roflumilast |
Primary outcome
Assessment of efficacy of Roflumlilast regarding control of patients with non cystic fibrosis bronchiectasis
Time frame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of Roflumilast on severity of symptoms in patients with bronchiectasis. Frequency of Exacerbation in the three months assessment and need of hospitalization will be the main parameter for efficacy of the new treatment described as number/ 3 months
Assessment of efficacy of roflumlilast in change of performance in patients with non cystic fibrosis bronchiectasis
Time frame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumilast on change dyspnea scale namely mMRCP evaluated at the start of the study and after 1 month and 3 months
Assessment of efficacy of roflumlilast on change in Pulmonary function in patients with non cystic fibrosis bronchiectasis
Time frame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumilast on change in pulmonary function test in patients with bronchiectasis regarding : change in FEV1 by liter per second
Assessment of efficacy of roflumlilast on change of symptoms in patients with non cystic fibrosis bronchiectasis
Time frame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).
Assessment of efficacy of roflumlilast on severity of symptoms in patients with bronchiactasis evaluated by bronchectasis severity index (FACED) score.
Assessment of efficancy of roflumlilast on change in systemic inflammation in patients with non cystic fibrosis bronchiectasis
Time frame: 3months . outcomes will be evaluated after 1 month and at the end of the study (3 months).
Assessment of efficacy of roflumlilast on systemic inflammation in patients with bronchiectasis regarding CRP by mg per L
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2019.
- Background: PubMed 20103769Sousa LP, Lopes F, Silva DM, Tavares LP, Vieira AT, Rezende BM, Carmo AF, Russo RC, Garcia CC, Bonjardim CA, Alessandri AL, Rossi AG, Pinho V, Teixeira MM. PDE4 inhibition drives resolution of neutrophilic inflammation by inducing apoptosis in a PKA-PI3K/Akt-dependent and NF-kappaB-independent manner. J Leukoc Biol. 2010 May;87(5):895-904. doi: 10.1189/jlb.0809540. Epub 2010 Jan 26.
- Background: PubMed 11986413Barker AF. Bronchiectasis. N Engl J Med. 2002 May 2;346(18):1383-93. doi: 10.1056/NEJMra012519. No abstract available.
- Background: PubMed 17573446Grootendorst DC, Gauw SA, Verhoosel RM, Sterk PJ, Hospers JJ, Bredenbroker D, Bethke TD, Hiemstra PS, Rabe KF. Reduction in sputum neutrophil and eosinophil numbers by the PDE4 inhibitor roflumilast in patients with COPD. Thorax. 2007 Dec;62(12):1081-7. doi: 10.1136/thx.2006.075937. Epub 2007 Jun 15.
- Background: PubMed 16083782van Schalkwyk E, Strydom K, Williams Z, Venter L, Leichtl S, Schmid-Wirlitsch C, Bredenbroker D, Bardin PG. Roflumilast, an oral, once-daily phosphodiesterase 4 inhibitor, attenuates allergen-induced asthmatic reactions. J Allergy Clin Immunol. 2005 Aug;116(2):292-8. doi: 10.1016/j.jaci.2005.04.023.
- 2\. King PT, Holdsworth SR, Freezer NJ, Villanueva E, Holmes PW. Characterisation of the onset and presenting clinical features of adult bronchiectasis. Respir Med. 2006;100:2183-2189. \[PubMed\] \[Google Scholar\]Link provided by the sponsor.
- The preclinical pharmacology of roflumilast--a selective, oral phosphodiesterase 4 inhibitor in development for chronic obstructive pulmonary disease.Pulm Pharmacol Ther 2010;23:235-56. 10.1016/j.pupt.201Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. the investigator group is welling to share all Data after finishing the study
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Bronchiectasis
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.
Ahmad Shaddad, Lecturer principal investigator
Assuit University - Assuit - Egypt
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Roflumilast in people with Bronchiectasis, run by Assiut University.
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 4 inclusion and 7 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: status not confirmed, as of the sponsor's last update on 3 Oct 2019. 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 phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Maha Ahmed Okasha, Resident (01002660421, maha.ahmed201388@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Assessment of efficacy of Roflumlilast regarding control of patients with non cystic fibrosis bronchiectasis (time frame: 3months . outcomes will be evaluated after 1month and at the end of the study (3months).). The study lists 5 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 NCT04090294, which also lists 4 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 3 Oct 2019.