Roflumilast on Markers of Bone Metabolism and Endothelial Function in COPD

• ClinicalTrials.gov Identifier: NCT01745848
• Recruitment Status: Completed
• First Posted: December 10, 2012
• Results First Posted: August 29, 2017
• Last Update Posted: August 29, 2017
• Sponsor: University of Pittsburgh
• Information provided by (Responsible Party): Jessica Bon Field, University of Pittsburgh

Tracking Information

• First Submitted Date: December 6, 2012
• First Posted Date: December 10, 2012
• Results First Submitted Date: June 5, 2017
• Results First Posted Date: August 29, 2017
• Last Update Posted Date: August 29, 2017
• Study Start Date: February 2013
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: July 27, 2017)

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)) [ Time Frame: 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.

• Original Primary Outcome Measures (submitted: December 7, 2012): systemic markers of bone metabolism [ Time Frame: 30 days ]

Current Secondary Outcome Measures (submitted: July 27, 2017)

Absolute Change From Baseline of Measurements of Brachial Artery Flow Mediated Dilation [ Time Frame: 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.

• Original Secondary Outcome Measures (submitted: December 7, 2012): endothelial function [ Time Frame: 30 days ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Roflumilast on Markers of Bone Metabolism and Endothelial Function in COPD
• Official Title: Effect of Roflumilast on Systemic Markers of Bone Metabolism and Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease
• 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.
• Study Type: Interventional
• Study Phase: Phase 4

Study Design

Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Masking Description:

Open Label

Primary Purpose: Treatment

• Condition: Chronic Obstructive Pulmonary Disease

Intervention

Drug: Roflumilast

Other Names:

• Daxas
• Daliresp

Study Arms

Experimental: Study Drug

Roflumilast 500 μcg, once daily, for 30 days

Intervention: Drug: Roflumilast

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: September 26, 2016): 26
• Original Estimated Enrollment (submitted: December 7, 2012): 20
• Actual Study Completion Date: June 30, 2016
• Actual Primary Completion Date: June 2016 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 50 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01745848
• Other Study ID Numbers: PRO12060615
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Jessica Bon Field, University of Pittsburgh
• Study Sponsor: University of Pittsburgh
• Collaborators: Not Provided

Investigators

• Principal Investigator: Jessica Bon Field, MD, MS; University of Pittsburgh

• PRS Account: University of Pittsburgh
• Verification Date: July 2017