COPDPhase 3NCT02340520

Enhancement of Corticosteroid Efficacy in COPD

A Phase 3 study testing Theophylline and Roflumilast in people with COPD, run by UConn Health at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 45 years and older
Conditions the study is for: COPD
What is being tested?: Theophylline and Roflumilast
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 13 participants
Where: 1 siteUnited States
Study dates: Dec 2014to Aug 2016
Phase: Phase 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 45 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Established diagnosis of COPD with FEV1 <60% predicted
FEV1/FVC <70% and <+15% FEV1 response to bronchodilator.
Patients of both genders will be included.
IRB approved written informed consent will be obtained from each subject.

Who cannot join

Recent (<1 month) exacerbation of COPD,
Known hypersensitivity to beta agonists, theophylline, steroids, or roflumilast.
Current or recent (<2 weeks) treatment with oral steroids, theophylline or other methylxanthines, or roflumlast.
Diagnosis or history of asthma, uncontrolled hypertension, or congestive heart failure.
History of Cardiac arrhythmia
History of seizures.

Show all 10Show fewer

History of Liver disease
Gastrointestinal disease, including history of peptic ulcer disease.
Current infection or antibiotic treatment.
History of depression or psychiatric disease.

Trial locations and contacts

1 site in 1 country.

United States1 site

UConnHealth
Farmington, Connecticut, 06032

Other trials in United States

About this study

This is a pilot study designed to evaluate the effects of theophylline and roflumilast on circulating Histone deacetylase (HDAC) levels in subjects with COPD, and the bronchodilator effects of corticosteroids. Studies will be performed in 10 subjects with COPD nonresponsive to bronchodilators. Subjects will receive theophylline tablets for 1 week, followed by measurement of circulating HDAC and the acute effect of oral prednisone on the bronchodilator response to inhaled beta agonist. Roflumilast tablets will be added to the theophylline for a further week and the studies repeated. The study will provide preliminary data on the effects of theophylline and roflumilast on circulating HDAC levels and the effects of corticosteroids on the beta agonist bronchodilator response in COPD.

Read the detailed description

SUBJECTS: 10 Stable patients >45 years of age, with an established diagnosis of COPD (18), with FEV1 <60% predicted, FEV1/FVC <70% and <+15% FEV1 response to bronchodilator will be recruited. Patients of both genders will be included.
TESTS
Blood: i) HDAC 2 in peripheral blood mononuclear cells: ii) Serum theophylline level b) Spirometry for measurement of FVC, FEV1 and FEV1/FVC PROCEDURES Visit 1.
After providing informed consent, subjects will receive a brief history and physical examination
Blood will be drawn from a peripheral vein for HDAC2 levels (2 ml).
Each subject will undergo baseline spirometry, which will be repeated after 3 inhalations of an albuterol inhaler.
Subjects will be asked to continue their regular treatment regimen, including long and short acting beta agonists and anticholinergics, as well as inhaled steroids.
Theophylline tablets extended-release 12 hr formulation, 300 mg orally taken every 12 hr will be dispensed, and the subject will return one week later for Visit 2. The subject will be asked to refrain from using his/her long acting beta agonists and anticholinergics for one day (24 hours) prior to Visit 2, and not to use the short acting beta agonist or take any caffeine containing drinks on the morning of visit 2. The subject will be asked to inform the P. I. should there be any adverse event. Subjects discontinuing the study drugs because of side effects will be withdrawn from the study. Visit 2.
A brief history and physical examination will be performed and the subject will be asked about any change in symptoms.
Blood (5 ml) will be drawn from a peripheral vein for HDAC2 and theophylline levels
After baseline spirometry the subject will be given a single dose of 40 mg prednisone tablets.
After 120 minutes, spirometry will be repeated, followed by 3 puffs of albuterol inhaler and repeat spirometry. The subject will then be asked to continue the theophylline tablets and in addition will be given roflumilast tablets 500 mcg orally once daily, and asked to return one week later for Visit 3. The subject will be asked to refrain from using his/her long acting beta agonists and anticholinergics for one day (24 hours) prior to Visit 3, and not to use the short acting beta agonist or take any caffeine containing drinks on the morning of visit 3. The subject will be asked to inform the P. I. should there be any adverse event. Visit 3
A brief history and physical examination will be performed and the subject will be asked about any change in symptoms.
Blood (5 ml) will be drawn from a peripheral vein for HDAC2 measurement.
After baseline spirometry the subject will be given a single dose of prednisone tablets in a dose of 40 mg.
After 120 minutes, spirometry will be repeated, followed by 3 puffs of albuterol inhaler and repeat spirometry. The subject will then have completed the study and will return to his/her previous treatment regimen. Data analysis: Results will be compared in terms of baseline vs drug by paired t test for change in FEV1 and FEV1/FVC as well as peripheral blood mononuclear blood HDAC2 levels. The relationship between FEV1 and FEV1/FVC and blood HDAC2 levels will be examined by correlation analysis. Expected results It is expected that with both theophylline and roflumilast treatment there will be a significant (p<0.05) increase in HDAC2 levels. It is also expected that with both theophylline and roflumilast treatment there will be a significant (p<0.05) increase in the bronchodilator response after the steroid dose, thereby supporting the hypothesis. It is also possible that there will be no effect on spirometry of either treatment; this would indicate that an increase in HDAC2 does not improve steroid responsiveness.

Conditions: COPD
Being tested: Theophylline, Roflumilast
Medical subject headings: Pulmonary Disease, Chronic Obstructive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

TheophyllineDrug
Oral
RoflumilastDrug
Oral

Study groups in NCT02340520
Study group	Role	What they receive
thophylline and roflumilast	Experimental	Theophylline for one week, followed by the addition of Roflumilast for a further one week. Receives: Drug: Theophylline; Drug: Roflumilast

What is being measured

The primary outcome is the main question the study is designed to answer.

Bronchodilation
Change in FEV1 L and FVC L
Measured: Baseline, Week 1 and 2

Secondary outcomes (1)

Change in HDAC2 Levels
circulating Histone Deacetylase2 levels measured in blood sample
Measured: Baseline, Week 1 and 2

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Dec 2014Aug 2016

First posted16 Jan 2015 (estimated)
Study startDec 2014
Primary completionAug 2016
Study completionAug 2016

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 COPDStudies 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 3
Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Enrolment: 13 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02340520
Sponsor's protocol ID: 14-032-3
Status last verified: May 2018
First submitted: 13 Jan 2015
Last updated: 19 Jun 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All COPD trials

Study at a glance

From the registry record, last updated by the sponsor on 19 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Enhancement of Corticosteroid Efficacy in COPD
ClinicalTrials.gov ID: NCT02340520
Acronym / sponsor ID: 14-032-3
Conditions: COPD
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 13 participants (actual)
Lead sponsor: UConn HealthUniversity, hospital or other
Study start: Dec 2014
Primary completion: Aug 2016 (actual)
Study completion: Aug 2016 (actual)
First posted: 16 Jan 2015 (estimated)
Results: Posted 19 Jun 2018

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

SUBJECTS: 10 Stable patients >45 years of age, with an established diagnosis of COPD (18), with FEV1 <60% predicted, FEV1/FVC <70% and <+15% FEV1 response to bronchodilator will be recruited. Patients of both genders will be included.
TESTS
Blood: i) HDAC 2 in peripheral blood mononuclear cells: ii) Serum theophylline level b) Spirometry for measurement of FVC, FEV1 and FEV1/FVC PROCEDURES Visit 1.
After providing informed consent, subjects will receive a brief history and physical examination
Blood will be drawn from a peripheral vein for HDAC2 levels (2 ml).
Each subject will undergo baseline spirometry, which will be repeated after 3 inhalations of an albuterol inhaler.
Subjects will be asked to continue their regular treatment regimen, including long and short acting beta agonists and anticholinergics, as well as inhaled steroids.
Theophylline tablets extended-release 12 hr formulation, 300 mg orally taken every 12 hr will be dispensed, and the subject will return one week later for Visit 2. The subject will be asked to refrain from using his/her long acting beta agonists and anticholinergics for one day (24 hours) prior to Visit 2, and not to use the short acting beta agonist or take any caffeine containing drinks on the morning of visit 2. The subject will be asked to inform the P. I. should there be any adverse event. Subjects discontinuing the study drugs because of side effects will be withdrawn from the study. Visit 2.
A brief history and physical examination will be performed and the subject will be asked about any change in symptoms.
Blood (5 ml) will be drawn from a peripheral vein for HDAC2 and theophylline levels
After baseline spirometry the subject will be given a single dose of 40 mg prednisone tablets.
After 120 minutes, spirometry will be repeated, followed by 3 puffs of albuterol inhaler and repeat spirometry. The subject will then be asked to continue the theophylline tablets and in addition will be given roflumilast tablets 500 mcg orally once daily, and asked to return one week later for Visit 3. The subject will be asked to refrain from using his/her long acting beta agonists and anticholinergics for one day (24 hours) prior to Visit 3, and not to use the short acting beta agonist or take any caffeine containing drinks on the morning of visit 3. The subject will be asked to inform the P. I. should there be any adverse event. Visit 3
A brief history and physical examination will be performed and the subject will be asked about any change in symptoms.
Blood (5 ml) will be drawn from a peripheral vein for HDAC2 measurement.
After baseline spirometry the subject will be given a single dose of prednisone tablets in a dose of 40 mg.
After 120 minutes, spirometry will be repeated, followed by 3 puffs of albuterol inhaler and repeat spirometry. The subject will then have completed the study and will return to his/her previous treatment regimen. Data analysis: Results will be compared in terms of baseline vs drug by paired t test for change in FEV1 and FEV1/FVC as well as peripheral blood mononuclear blood HDAC2 levels. The relationship between FEV1 and FEV1/FVC and blood HDAC2 levels will be examined by correlation analysis. Expected results It is expected that with both theophylline and roflumilast treatment there will be a significant (p<0.05) increase in HDAC2 levels. It is also expected that with both theophylline and roflumilast treatment there will be a significant (p<0.05) increase in the bronchodilator response after the steroid dose, thereby supporting the hypothesis. It is also possible that there will be no effect on spirometry of either treatment; this would indicate that an increase in HDAC2 does not improve steroid responsiveness.

Study design

Primary purpose: Treatment
Allocation: Not applicable
Intervention model: Single group
Masking: None (open label)
Number of arms: 1

Arm	Type	Receives
thophylline and roflumilast	Experimental	Drug: Theophylline, Drug: RoflumilastTheophylline for one week, followed by the addition of Roflumilast for a further one week.

Who may qualify

Ages: 45 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (4 listed)

Established diagnosis of COPD with FEV1 <60% predicted
FEV1/FVC <70% and <+15% FEV1 response to bronchodilator.
Patients of both genders will be included.
IRB approved written informed consent will be obtained from each subject.

Key exclusion criteria (10 listed)

Recent (<1 month) exacerbation of COPD,
Known hypersensitivity to beta agonists, theophylline, steroids, or roflumilast.
Current or recent (<2 weeks) treatment with oral steroids, theophylline or other methylxanthines, or roflumlast.
Diagnosis or history of asthma, uncontrolled hypertension, or congestive heart failure.
History of Cardiac arrhythmia

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
TheophyllineOral	Drug	thophylline and roflumilast
RoflumilastOral	Drug	thophylline and roflumilast

Primary outcome

Bronchodilation
Time frame: Baseline, Week 1 and 2
Change in FEV1 L and FVC L

1 secondary outcome

Change in HDAC2 Levels
Time frame: Baseline, Week 1 and 2

Results and safety

Results posted to the registry on 19 Jun 2018, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Theophylline and Roflumilast	11	8

Primary outcome: Bronchodilation

Time frame: Baseline, Week 1 and 2. Mean (Standard Deviation). Unit: liters

Measure	Theophylline and Roflumilast n = 8
baseline FEV1	1.18 (0.51)
baseline FVC	2.72 (0.78)
week 1 FEV1	1.22 (0.51)
week 1 FVC	2.90 (0.82)
post steroid week 1 FEV1	1.18 (0.51)
post steroid week 1 FVC	2.72 (0.68)
week 2 FEV1	1.25 (0.58)
week 2 FVC	2.79 (0.71)

Theophylline and Roflumilast: p >0.05, t-test, 2 sided

1 secondary outcome is reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Theophylline and Roflumilast	0 of 11 (0%)	0 of 11 (0%)	0 of 11

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 19 Jun 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.

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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.

Nausherwan Burki principal investigator

UConn Health

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Theophylline and Roflumilast in people with COPD, run by UConn Health 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 4 inclusion and 10 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 19 Jun 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 phase mean?

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 19 Jun 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?

Bronchodilation (time frame: Baseline, Week 1 and 2). 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 NCT02340520.

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 19 Jun 2018.