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

This study has been terminated.
(The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.)
Sponsor:
Collaborators:
Innovair
Takeda
Information provided by (Responsible Party):
Laval University
ClinicalTrials.gov Identifier:
NCT01701934
First received: October 3, 2012
Last updated: November 10, 2014
Last verified: November 2014

October 3, 2012
November 10, 2014
February 2013
October 2014   (final data collection date for primary outcome measure)
Change in intrabdominal adiposity [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
Measured by CT scan.
Same as current
Complete list of historical versions of study NCT01701934 on ClinicalTrials.gov Archive Site
  • 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
  • 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, apoB, LDL/HDL cholesterol, CRP-HS will be measured.
  • Change in body composition [ Time Frame: At baseline and 6 months later ] [ Designated as safety issue: No ]
    As measured by 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
Not Provided
Not Provided
 
Impact of Roflumilast on Visceral Adiposity and Metabolic Profile in Chronic Obstructive Pulmonary Disease
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).

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
  • Chronic Obstructive Pulmonary Disease
  • Metabolic Syndrome
  • Drug: Roflumilast
    500 mcg, oral, once daily for 6 months
    Other Name: DAXAS
  • Drug: Placebo
    One placebo pill daily, for 6 months
    Other Name: Inactive comparator
  • Experimental: Roflumilast
    Roflumilast 500 mcg, once daily for 6 months
    Intervention: Drug: Roflumilast
  • Placebo Comparator: Placebo pill
    Placebo pill, once daily for 6 months
    Intervention: Drug: Placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
14
December 2014
October 2014   (final data collection date for primary outcome measure)

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
Male
40 Years to 80 Years
No
Contact information is only displayed when the study is recruiting subjects
Canada
 
NCT01701934
RAMBO
Yes
Laval University
Laval University
  • Innovair
  • Takeda
Principal Investigator: François Maltais, MD Institut universitaire de cardiologie et de pneumologie de Québec
Laval University
November 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP