Roflumilast on Markers of Bone Metabolism and Endothelial Function in COPD

Effect of Roflumilast on Systemic Markers of Bone Metabolism and Endothelial Function in Patients With Chronic Obstructive Pulmonary Disease

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Roflumilast

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
• Enrollment (Actual): 26
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Emphysema COPD Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Study Drug; Roflumilast 500 μcg, once daily, for 30 days	Drug: Roflumilast; Other Names: Daliresp; Daxas

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	30 days - measurements at baseline and 30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	30 days - measured at baseline and 30 days

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): June 1, 2016
• Study Completion (ACTUAL): June 30, 2016

Study Registration Dates

• First Submitted: December 6, 2012
• First Submitted That Met QC Criteria: December 7, 2012
• First Posted (ESTIMATE): December 10, 2012

Study Record Updates

• Last Update Posted (ACTUAL): August 29, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Keywords: COPD; Roflumilast
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive
• Other Study ID Numbers: PRO12060615