Chronic Obstructive Pulmonary Disease
Conditions
Keywords
Roflumilast, COPD
Brief summary
Our primary hypothesis is that Roflumilast (500 μcg, once daily) will significantly decrease surrogate markers of bone metabolism and early cardiovascular disease in individuals with moderate to severe airflow obstruction and a chronic bronchitis phenotype.
Detailed description
Study participants will be given Roflumilast 500 micrograms daily for 30 days. At baseline, prior to drug administration, blood samples will be collected for analysis of markers of bone metabolism (C-terminal telopeptide of Type I Collagen (CTx), Amino-terminal Propeptide of Type-1 Procollagen (P1NP) and participants will undergo measurement of endothelial function with measurement of brachial flow mediated dilation. After completion of one month of Roflumilast therapy, participants will have a repeat blood collection for measurement of CTx and P1NP and repeat measurement of brachial flow mediated dilation testing.
Interventions
DRUGRoflumilast
Sponsors
University of Pittsburgh
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open Label
Eligibility
Sex/Gender
ALL
Age
50 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Subjects between the ages of 50 and 70 with a minimum of ten-pack years of tobacco exposure, airflow obstruction (FEV1/FVC \< 0.70) with an FEV1 \< 70% * baseline sputum production at least some of the time as reported on the Saint George's Respiratory Questionnaire, and at least one exacerbation within the past year
Exclusion criteria
* Subjects with chronic prednisone use, antiresorptive therapy use (bisphosphonates, calcitonin, parathyroid hormone) * Subjects with a body mass index less than 18 or greater than 34
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline of Systemic Markers of Bone Metabolism (C-terminal Peptide of Type 1 Collagen (CTx) and Amino-terminal Propeptide of Type-1 Procollagen (P1NP)) | 30 days - measurements at baseline and 30 days | Serum samples were obtained at baseline and after participants took a once daily, 500 mcg roflumilast dose for 30 days. Samples were obtained in the semi-fasting state, processed, and stored for batch analysis at the end of the study. C-terminal peptide of type 1 collagen (CTx), a marker of bone resorption, was analyzed using a commercially available immunoassay (Roche Elecsys 2010 analyzer, Roche Diagnostics, Manheim, Germany). Serum amino-terminal propeptide of type-1 procollagen (P1NP) was measured by ELISA (MyBioSource, San Diego, CA). All assays were performed according to the manufacturers' instructions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Absolute Change From Baseline of Measurements of Brachial Artery Flow Mediated Dilation | 30 days - measured at baseline and 30 days | Participants had flow mediated dilation of the brachial artery measured at the baseline visit and at the follow-up visit after receiving 30 days of roflumilast 500 mcg daily. An ultrasound probe was placed over the brachial artery and the brachial artery diameter was measured in real time. A blood pressure cuff positioned below the elbow was then inflated to 50 mmHg above systolic pressure for five minutes. After five minutes of occlusion, the blood pressure cuff was released and the brachial artery diameter was again measured in real time. The amount of dilation expressed as the absolute change, in millimeters, from baseline diameter was quantified using the ultrasound images obtained 60 seconds after cuff release. |
Countries
United States
Participant flow
Pre-assignment details
All participants enrolled were assigned to the roflumilast group (no control arm of this study).
Participants by arm
| Arm | Count |
|---|---|
| Roflumilast Roflumilast 500 μcg, once daily, for 30 days | 26 |
| Total | 26 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
Baseline characteristics
| Characteristic | Roflumilast |
|---|---|
| Age, Continuous | 65.3 years |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 24 Participants |
| Region of Enrollment United States | 26 participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 26 |
| other Total, other adverse events | 6 / 26 |
| serious Total, serious adverse events | 0 / 26 |
Outcome results
Primary
Change From Baseline of Systemic Markers of Bone Metabolism (C-terminal Peptide of Type 1 Collagen (CTx) and Amino-terminal Propeptide of Type-1 Procollagen (P1NP))
Serum samples were obtained at baseline and after participants took a once daily, 500 mcg roflumilast dose for 30 days. Samples were obtained in the semi-fasting state, processed, and stored for batch analysis at the end of the study. C-terminal peptide of type 1 collagen (CTx), a marker of bone resorption, was analyzed using a commercially available immunoassay (Roche Elecsys 2010 analyzer, Roche Diagnostics, Manheim, Germany). Serum amino-terminal propeptide of type-1 procollagen (P1NP) was measured by ELISA (MyBioSource, San Diego, CA). All assays were performed according to the manufacturers' instructions.
Time frame: 30 days - measurements at baseline and 30 days
Population: Data were analyzed for the 20 participants completing baseline and follow-up visits after one month on study drug.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Roflumilast | Change From Baseline of Systemic Markers of Bone Metabolism (C-terminal Peptide of Type 1 Collagen (CTx) and Amino-terminal Propeptide of Type-1 Procollagen (P1NP)) | change in CTx levels from baseline to 30-days | 0.079 ng/mL | Standard Deviation 0.096 |
| Roflumilast | Change From Baseline of Systemic Markers of Bone Metabolism (C-terminal Peptide of Type 1 Collagen (CTx) and Amino-terminal Propeptide of Type-1 Procollagen (P1NP)) | change in P1NP levels from baseline to 30 days | -101.77 ng/mL | Standard Deviation 246.53 |
Secondary
Absolute Change From Baseline of Measurements of Brachial Artery Flow Mediated Dilation
Participants had flow mediated dilation of the brachial artery measured at the baseline visit and at the follow-up visit after receiving 30 days of roflumilast 500 mcg daily. An ultrasound probe was placed over the brachial artery and the brachial artery diameter was measured in real time. A blood pressure cuff positioned below the elbow was then inflated to 50 mmHg above systolic pressure for five minutes. After five minutes of occlusion, the blood pressure cuff was released and the brachial artery diameter was again measured in real time. The amount of dilation expressed as the absolute change, in millimeters, from baseline diameter was quantified using the ultrasound images obtained 60 seconds after cuff release.
Time frame: 30 days - measured at baseline and 30 days
Population: Data were analyzed for the 20 participants completing baseline and follow-up visits after one month on study drug.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Roflumilast | Absolute Change From Baseline of Measurements of Brachial Artery Flow Mediated Dilation | 0.335 millimeters | Standard Deviation 4.63 |