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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Innovair
Takeda
Information provided by (Responsible Party):
Laval University
ClinicalTrials.gov Identifier:
NCT01701934
First received: October 3, 2012
Last updated: July 17, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Chronic Obstructive Pulmonary Disease
Metabolic Syndrome
Drug: Roflumilast
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Impact of Roflumilast on Visceral Adiposity and MetaBolic Profile in Chronic Obstructive Lung Disease: a Randomized and Controlled Trial: the RAMBO Trial.

Resource links provided by NLM:


Further study details as provided by Laval University:

Primary Outcome Measures:
  • Change in intrabdominal adiposity [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    Measured by CT scan.


Secondary Outcome Measures:
  • Change in body mass index [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
  • Change in waist circumference [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
  • Change in waist-to-hip circumference ratio [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
  • Change in blood metabolic profile [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    Blood glucose, insulin, triglycerides, apolipoprotein B, LDL/HDL cholesterol, C-reactive protein will be measured.

  • Change in body composition [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    As measured by dual-energy X-ray absorptiometry (DEXA).

  • Change in subcutaneous adiposity [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    As measured by CT scan.

  • Change in liver fat [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    As measured by CT scan


Estimated Enrollment: 122
Study Start Date: February 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Roflumilast
Roflumilast 500 mcg, once daily for 6 months
Drug: Roflumilast
500 mcg, oral, once daily for 6 months
Other Name: DAXAS
Placebo Comparator: Placebo pill
Placebo pill, once daily for 6 months
Drug: Placebo
One placebo pill daily, for 6 months
Other Name: Inactive comparator

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.

  Eligibility

Ages Eligible for Study:   40 Years to 80 Years
Genders Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01701934

Locations
Canada, British Columbia
St. Paul's Hospital
Vancouver, British Columbia, Canada, V6Z 1Y6
Canada, Quebec
Montreal Chest Institute
Montréal, Quebec, Canada, H2X 2P4
Centre hospitalier de l'Université de Montréal
Montréal, Quebec, Canada, H2W 1T8
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, Canada, G1V 4G5
Hôpital régional de Saint-Jérôme
Saint-Jérôme, Quebec, Canada, J7Z 5T3
Sponsors and Collaborators
Laval University
Innovair
Takeda
Investigators
Principal Investigator: François Maltais, MD Institut universitaire de cardiologie et de pneumologie de Québec
  More Information

Publications:

Responsible Party: Laval University
ClinicalTrials.gov Identifier: NCT01701934     History of Changes
Other Study ID Numbers: RAMBO
Study First Received: October 3, 2012
Last Updated: July 17, 2014
Health Authority: Canada: Health Canada

Keywords provided by Laval University:
COPD
Intrabdominal adiposity
Body composition
Triglycerides
Cholesterol

Additional relevant MeSH terms:
Metabolic Syndrome X
Lung Diseases
Respiration Disorders
Pulmonary Disease, Chronic Obstructive
Obesity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases

ClinicalTrials.gov processed this record on July 22, 2014