Impact of Roflumilast on Visceral Adiposity and Metabolic Profile in Chronic Obstructive Pulmonary Disease (RAMBO)

November 10, 2014 updated by: Laval University

Impact of Roflumilast on Visceral Adiposity and MetaBolic Profile in Chronic Obstructive Lung Disease: a Randomized and Controlled Trial: the RAMBO Trial.

The purpose of this study is to determine whether roflumilast can improve metabolic profile and reduce visceral adiposity in patients with chronic obstructive pulmonary disease (COPD).

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

Although underweight has been the traditional nutritional concern in patients with COPD, overweight and obesity are becoming important issues in this disease. In a rehabilitation study, investigators found that 66% of patients with moderate to severe COPD were either overweight or obese according to the WHO obesity classification (BMI ≥ 25 kg/m2). Obesity and COPD being two frequent conditions, it is important to understand the nature of their interactions.

Obesity, particularly in its visceral form is associated with a plethora of metabolic consequences that increases the risk of cardiovascular diseases. This would seem relevant to COPD which is in itself an important risk factor for cardiovascular diseases. The presence of obesity, particularly visceral obesity, may thus define in patients with COPD a clinical phenotype at high risk of cardiovascular diseases. In this context, it is relevant to note that the prevalence of metabolic syndrome is increased in COPD. Although fat distribution has not been precisely assessed in COPD studies, increased waist circumference is common in this disease suggesting that visceral obesity is part of the obesity syndrome seen in COPD.

Given the relationship between COPD, obesity and the metabolic syndrome and cardiovascular diseases, it is tempting to suggest that visceral obesity is likely to be frequent in COPD (as in the general population) and that the profound metabolic and inflammatory perturbations associated with this form of overweight/obesity could play a central role in the link between COPD and cardiovascular diseases.

Roflumilast, a Phosphodiesterase-4 inhibitor, has been recently evaluated as an anti-inflammatory medication in patients with COPD. Roflumilast, alone or in combination with long-acting bronchodilators, provide modest but significant improvement in lung function along with reductions in the rate of exacerbation in patients with moderate to severe COPD. A very interesting observation that was made in these 12-month duration studies was that the use of roflumilast was associated with an average reduction in body weight of 2 kg that took place during the first 6 months of the trials and remained relatively stable throughout the rest of the trials. The mechanisms and the precise effects of roflumilast on body composition and adipose tissue distribution have not been studied in great detail. However, available data suggest that roflumilast induces a preferential loss in body fat mass in comparison to fat-free mass. It remains to be seen whether roflumilast specifically affects visceral versus subcutaneous adipose tissue. The improved insulin sensitivity reported in one study in the presence of an apparently trivial weight loss (0.7 kg compared to placebo) may suggest that a selective loss of visceral adipose tissue may have been produced in response to roflumilast therapy.

These observations, although not definitive, suggest that roflumilast could be used not only to treat the respiratory component of COPD but also to modulate the metabolic aspect of this disease including visceral adiposity, features of the metabolic syndrome and significant co-morbidities of COPD.

Study Type

Interventional

Enrollment (Actual)

14

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6Z 1Y6
        • St. Paul's Hospital
    • Quebec
      • Montréal, Quebec, Canada, H2W 1T8
        • Centre Hospitalier de l'Université de Montréal
      • Montréal, Quebec, Canada, H2X 2P4
        • Montreal Chest Institute
      • Québec, Quebec, Canada, G1V 4G5
        • Institut Universitaire de cardiologie et de pneumologie de Quebec
      • Saint-Jérôme, Quebec, Canada, J7Z 5T3
        • Hôpital régional de Saint-Jérôme

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

40 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Male

Description

Inclusion Criteria:

  • Gave an informed consent
  • Forced expiratory volume in 1 second < 80% predicted
  • Forced expiratory volume in 1 second / Forced vital capacity < 70%
  • No exacerbation in the last 4 weeks
  • Current or ex-smoker
  • Smoking history of at least 10 pack/year
  • Body mass index of at least 25 kg/m2
  • Waist circumference of at least 94 cm
  • Fasting blood triglycerides of at least 1.7 mmol/L

Exclusion Criteria:

  • Any significant pulmonary pathology other than COPD
  • Under oxygen therapy more than 12 hours per day
  • More than 2 exacerbation episodes in the last 12 months
  • The patient is currently participating to the active phase of a rehabilitation program
  • Patient has been under roflumilast therapy prior to enrollment
  • Unstable hypertriglyceridemia or hypercholesterolemia
  • Under diabetes therapy (hypoglycemic agent or insulin)
  • Cancer history in the last 5 years (except basal cell carcinoma)
  • Moderate or severe hepatic impairment
  • Used prednisone or systemic corticosteroids in the last 4 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Roflumilast
Roflumilast 500 mcg, once daily for 6 months
Drug: Roflumilast
500 mcg, oral, once daily for 6 months
Other Names:
  • DAXAS
Placebo Comparator: Placebo pill
Placebo pill, once daily for 6 months
Drug: Placebo
One placebo pill daily, for 6 months
Other Names:
  • Inactive comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in intrabdominal adiposity
Time Frame: At baseline and 6 months later
Measured by CT scan.
At baseline and 6 months later

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in body mass index
Time Frame: At baseline and 6 months later
At baseline and 6 months later
Change in waist circumference
Time Frame: At baseline and 6 months later
At baseline and 6 months later
Change in waist-to-hip circumference ratio
Time Frame: At baseline and 6 months later
At baseline and 6 months later
Change in blood metabolic profile
Time Frame: At baseline and 6 months later
Blood glucose, insulin, triglycerides, apolipoprotein B, LDL/HDL cholesterol, C-reactive protein will be measured.
At baseline and 6 months later
Change in body composition
Time Frame: At baseline and 6 months later
As measured by dual-energy X-ray absorptiometry (DEXA).
At baseline and 6 months later
Change in subcutaneous adiposity
Time Frame: At baseline and 6 months later
As measured by CT scan.
At baseline and 6 months later
Change in liver fat
Time Frame: At baseline and 6 months later
As measured by CT scan
At baseline and 6 months later

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Laval University

Collaborators

Takeda
Innovair

Investigators

  • Principal Investigator: François Maltais, MD, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2013

Primary Completion (Actual)

October 1, 2014

Study Completion (Anticipated)

December 1, 2014

Study Registration Dates

First Submitted

October 3, 2012

First Submitted That Met QC Criteria

October 3, 2012

First Posted (Estimate)

October 5, 2012

Study Record Updates

Last Update Posted (Estimate)

November 11, 2014

Last Update Submitted That Met QC Criteria

November 10, 2014

Last Verified

November 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RAMBO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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