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

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Chronic Obstructive Pulmonary Disease
• Intervention: Drug: Roflumilast
• Enrollment: 26

Participant Flow

Recruitment Details
Pre-assignment Details	All participants enrolled were assigned to the roflumilast group (no control arm of this study).

Arm/Group Title	Roflumilast
Arm/Group Description	Roflumilast 500 μcg, once daily, for 30 days Roflumilast
Period Title: Overall Study
Started	26
Completed	20
Not Completed	6
Reason Not Completed
Adverse Event	6

Baseline Characteristics

Arm/Group Title		Roflumilast
Arm/Group Description		Roflumilast 500 μcg, once daily, for 30 days
Overall Number of Baseline Participants		26
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Mean (Full Range); Unit of measure: Years
	Number Analyzed	26 participants
		65.3; (55 to 74)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	Female	12 46.2%
	Male	14 53.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	26 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	2 7.7%
	White	24 92.3%
	More than one race	0 0.0%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	26 participants
		26

Outcome Measures

1. Primary Outcome

Title	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))
Description	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

Outcome Measure Data

Analysis Population Description

Data were analyzed for the 20 participants completing baseline and follow-up visits after one month on study drug.

Arm/Group Title	Roflumilast
Arm/Group Description:	Roflumilast 500 μcg, once daily, for 30 days
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: ng/mL
change in CTx levels from baseline to 30-days	0.079 (0.096)
change in P1NP levels from baseline to 30 days	-101.77 (246.53)

2. Secondary Outcome

Title	Absolute Change From Baseline of Measurements of Brachial Artery Flow Mediated Dilation
Description	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

Outcome Measure Data

Analysis Population Description

Data were analyzed for the 20 participants completing baseline and follow-up visits after one month on study drug.

Arm/Group Title	Roflumilast
Arm/Group Description:	Roflumilast 500 μcg, once daily, for 30 days
Overall Number of Participants Analyzed	20
Mean (Standard Deviation); Unit of Measure: millimeters
	0.335 (4.63)

Adverse Events

Time Frame	30 days for each participant
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	Roflumilast
Arm/Group Description	Roflumilast 500 μcg, once daily, for 30 days
All-Cause Mortality
	Roflumilast
	Affected / at Risk (%)
Total	0/26 (0.00%)
Serious Adverse Events
	Roflumilast
	Affected / at Risk (%)	# Events
Total	0/26 (0.00%)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	Roflumilast
	Affected / at Risk (%)	# Events
Total	6/26 (23.08%)
Gastrointestinal disorders
Gastrointestinal upset † [1]	3/26 (11.54%)	3
Gastrointestinal upset † [2]	3/26 (11.54%)	3
† Indicates events were collected by systematic assessment; [1] diarrhea after starting study drug; [2] nausea

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Dr. Jessica Bon Field
• Organization: University of Pittsburgh
• Phone: 412-648-6494
• EMail: bonjm@upmc.edu

• Responsible Party: Jessica Bon Field, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT01745848
• Other Study ID Numbers: PRO12060615
• First Submitted: December 6, 2012
• First Posted: December 10, 2012
• Results First Submitted: June 5, 2017
• Results First Posted: August 29, 2017
• Last Update Posted: August 29, 2017