Cystic FibrosisPhase 4NCT01323101
Doxycycline Effects on Inflammation in Cystic Fibrosis
A Phase 4 study testing Doxycycline and No doxycycline in people with Cystic Fibrosis, run by University of Southern California at 1 site in United States.
Trial summary
Doxycycline is known to exhibit immune modulatory activities beyond its antibacterial effects. In particular, doxycycline is a potent inhibitor of matrix metalloproteinase 9, which is a protease derived largely from neutrophils. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- Doxycycline and No doxycycline
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2008to Dec 2010
- Phase
- Phase 4
- 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
Who may be able to join
- Age greater than 18 years
- Clinically stable (FEV1 within 10% of baseline)
- FEV1 > 40% predicted
Who cannot join
- Use of clinically significant concomitant drug therapy such as long-term use of nonsteroidal anti-inflammatory drugs or corticosteroids
- Known hypersensitivity to doxycycline
- Pregnancy or attempting to conceive, breast feeding, initiation of or change in hormonal method of contraception within 4 weeks of baseline or during the study
- Use of systemic antibiotics (except oral azithromycin) within 4 weeks of baseline
- Use of doxycycline within 60 days of baseline
- Known history of gastrointestinal bleeding or gastrointestinal ulceration.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90089
About this study
Official title: Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.
Doxycycline is known to exhibit immune modulatory activities beyond its antibacterial effects. In particular, doxycycline is a potent inhibitor of matrix metalloproteinase 9, which is a protease derived largely from neutrophils. Recent studies demonstrate a significant correlation between pulmonary disease severity and sputum concentrations of MMP-9 in patients with CF. In addition, sputum MMP-9 levels are associated with airway remodeling in CF.
The goal of this study is to determine the therapeutic potential of doxycycline in modulating host airway inflammation in patients with CF. Specifically, the study will characterize the PK /PD of doxycycline, evaluate the safety of short term therapy, and explore the concentration effect relationship between doxycycline exposure and sputum biomarker levels.
Read the detailed description
This study will consist of a prospective, open-label, randomized, controlled trial conducted in 24 patients with cystic fibrosis. Twenty subjects will be stratified in a 1:2 ratio based on baseline FEV1 into mild (> 70%) or moderate (40-70%) pulmonary disease in order to control for disease severity within each dose level. The subjects will be randomized in blocks of four to receive no drug, 40mg, 100mg, or 200mg daily for 28 days.
Sputum samples will be obtained in all groups by induction with hypertonic saline at baseline, 8, 24, and 48 hours following the first dose and then weekly for 4 weeks. Sputum will also be collected at two follow up visits after the treatment period at weeks 5 and 6.
In the doxycycline group, serial blood samples (5 mL) for determination of doxycycline concentrations will be obtained before and at 0, 0.5, 1, 2, 4, 12, 24, and 48 hours following the 1-hr infusion of a single IV dose. Once daily dosing of doxycycline will resume immediately following the 48-hour blood sample and will continue until day 28. Additional levels will be obtained pre-dose, and 1, 2, and 3 hours after doses administered on days 14 and 28. A sample of blood will be obtained at baseline, and at days 28 for inflammatory marker analyses.
- Conditions
- Cystic Fibrosis
- Being tested
- Doxycycline, No doxycycline
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DoxycyclineDrug
Also called Doryx, Vibramycin
Doxycycline 40mg, 100mg, 200mg tablet once daily, or no drug for 28 days.
No doxycyclineOther
| Study group | Role | What they receive |
|---|---|---|
| Control | Sham comparator | No doxycycline Receives: Other: No doxycycline |
| Doxycycline | Experimental | Not described Receives: Drug: Doxycycline |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the effect of doxycycline on inflammatory biomarkers
Measured: Within 42 days
Secondary outcomes (1)
To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis
Measured: Within 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Mar 2011 (estimated)
- Study startApr 2008
- Primary completionDec 2010
- Study completionDec 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 University of Southern CaliforniaThe 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paul Beringer, University of Southern California
- Investigators
- Paul M Beringer, Pharm.D., Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01323101
- Sponsor's protocol ID
- HS-08-00017
- Status last verified
- Mar 2017
- First submitted
- 15 Feb 2011
- Last updated
- 30 Mar 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Beringer PM, Owens H, Nguyen A, Benitez D, Rao A, D'Argenio DZ. Pharmacokinetics of doxycycline in adults with cystic fibrosis. Antimicrob Agents Chemother. 2012 Jan;56(1):70-4. doi: 10.1128/AAC.05710-11. Epub 2011 Oct 24.
PubMed 22024822
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Doxycycline on Sputum Biomarkers of Inflammation and Lung Epithelial Repair in Patients With Cystic Fibrosis.
- ClinicalTrials.gov ID
- NCT01323101
- Acronym / sponsor ID
- HS-08-00017
- Conditions
- Cystic Fibrosis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Study start
- Apr 2008
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2010 (actual)
- First posted
- 25 Mar 2011 (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.
Doxycycline is known to exhibit immune modulatory activities beyond its antibacterial effects. In particular, doxycycline is a potent inhibitor of matrix metalloproteinase 9, which is a protease derived largely from neutrophils. Recent studies demonstrate a significant correlation between pulmonary disease severity and sputum concentrations of MMP-9 in patients with CF. In addition, sputum MMP-9 levels are associated with airway remodeling in CF.
The goal of this study is to determine the therapeutic potential of doxycycline in modulating host airway inflammation in patients with CF. Specifically, the study will characterize the PK /PD of doxycycline, evaluate the safety of short term therapy, and explore the concentration effect relationship between doxycycline exposure and sputum biomarker levels.
Detailed description
This study will consist of a prospective, open-label, randomized, controlled trial conducted in 24 patients with cystic fibrosis. Twenty subjects will be stratified in a 1:2 ratio based on baseline FEV1 into mild (> 70%) or moderate (40-70%) pulmonary disease in order to control for disease severity within each dose level. The subjects will be randomized in blocks of four to receive no drug, 40mg, 100mg, or 200mg daily for 28 days.
Sputum samples will be obtained in all groups by induction with hypertonic saline at baseline, 8, 24, and 48 hours following the first dose and then weekly for 4 weeks. Sputum will also be collected at two follow up visits after the treatment period at weeks 5 and 6.
In the doxycycline group, serial blood samples (5 mL) for determination of doxycycline concentrations will be obtained before and at 0, 0.5, 1, 2, 4, 12, 24, and 48 hours following the 1-hr infusion of a single IV dose. Once daily dosing of doxycycline will resume immediately following the 48-hour blood sample and will continue until day 28. Additional levels will be obtained pre-dose, and 1, 2, and 3 hours after doses administered on days 14 and 28. A sample of blood will be obtained at baseline, and at days 28 for inflammatory marker analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Sham comparator | Other: No doxycyclineNo doxycycline |
| Doxycycline | Experimental | Drug: Doxycycline |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Age greater than 18 years
- Clinically stable (FEV1 within 10% of baseline)
- FEV1 > 40% predicted
Key exclusion criteria (6 listed)
- Use of clinically significant concomitant drug therapy such as long-term use of nonsteroidal anti-inflammatory drugs or corticosteroids
- Known hypersensitivity to doxycycline
- Pregnancy or attempting to conceive, breast feeding, initiation of or change in hormonal method of contraception within 4 weeks of baseline or during the study
- Use of systemic antibiotics (except oral azithromycin) within 4 weeks of baseline
- Use of doxycycline within 60 days of baseline
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 |
|---|---|---|
| DoxycyclineAlso: Doryx, VibramycinDoxycycline 40mg, 100mg, 200mg tablet once daily, or no drug for 28 days. | Drug | Doxycycline |
| No doxycycline | Other | Control |
Primary outcome
To determine the effect of doxycycline on inflammatory biomarkers
Time frame: Within 42 days
1 secondary outcome
To characterize the pharmacokinetics, pharmacodynamics and safety of doxycycline in patients with cystic fibrosis
Time frame: Within 42 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 30 Mar 2017.
- Results publication: PubMed 22024822Beringer PM, Owens H, Nguyen A, Benitez D, Rao A, D'Argenio DZ. Pharmacokinetics of doxycycline in adults with cystic fibrosis. Antimicrob Agents Chemother. 2012 Jan;56(1):70-4. doi: 10.1128/AAC.05710-11. Epub 2011 Oct 24.
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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.
Paul M Beringer, Pharm.D. principal investigator
University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Doxycycline and No doxycycline in people with Cystic Fibrosis, run by University of Southern California 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 6 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 30 Mar 2017. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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?
To determine the effect of doxycycline on inflammatory biomarkers (time frame: Within 42 days). 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 NCT01323101, which also lists 1 linked publication.
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 30 Mar 2017.