Impact of Roflumilast on Visceral Adiposity and Metabolic Profile in Chronic Obstructive Pulmonary Disease (RAMBO)
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| ClinicalTrials.gov Identifier: NCT01701934 |
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Recruitment Status :
Terminated
(The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.)
First Posted : October 5, 2012
Last Update Posted : November 11, 2014
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Chronic Obstructive Pulmonary Disease Metabolic Syndrome | Drug: Roflumilast Drug: Placebo | Phase 2 |
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 (Clinical Trial) |
| Actual Enrollment : | 14 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Triple (Participant, 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. |
| Study Start Date : | February 2013 |
| Actual Primary Completion Date : | October 2014 |
| Estimated Study Completion Date : | December 2014 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Roflumilast
Roflumilast 500 mcg, once daily for 6 months
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Drug: Roflumilast
500 mcg, oral, once daily for 6 months
Other Name: DAXAS |
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Placebo Comparator: Placebo pill
Placebo pill, once daily for 6 months
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Drug: Placebo
One placebo pill daily, for 6 months
Other Name: Inactive comparator |
- Change in intrabdominal adiposity [ Time Frame: At baseline and 6 months later ]Measured by CT scan.
- Change in body mass index [ Time Frame: At baseline and 6 months later ]
- Change in waist circumference [ Time Frame: At baseline and 6 months later ]
- Change in waist-to-hip circumference ratio [ Time Frame: 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.
- Change in body composition [ Time Frame: At baseline and 6 months later ]As measured by dual-energy X-ray absorptiometry (DEXA).
- Change in subcutaneous adiposity [ Time Frame: At baseline and 6 months later ]As measured by CT scan.
- Change in liver fat [ Time Frame: At baseline and 6 months later ]As measured by CT scan
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| Ages Eligible for Study: | 40 Years to 80 Years (Adult, Older Adult) |
| Sexes Eligible for Study: | Male |
| Accepts Healthy Volunteers: | No |
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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01701934
| Canada, British Columbia | |
| St. Paul's Hospital | |
| Vancouver, British Columbia, Canada, V6Z 1Y6 | |
| Canada, Quebec | |
| Centre hospitalier de l'Université de Montréal | |
| Montréal, Quebec, Canada, H2W 1T8 | |
| Montreal Chest Institute | |
| Montréal, Quebec, Canada, H2X 2P4 | |
| 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 | |
| Principal Investigator: | François Maltais, MD | Institut universitaire de cardiologie et de pneumologie de Québec |
| Responsible Party: | Laval University |
| ClinicalTrials.gov Identifier: | NCT01701934 |
| Other Study ID Numbers: |
RAMBO |
| First Posted: | October 5, 2012 Key Record Dates |
| Last Update Posted: | November 11, 2014 |
| Last Verified: | November 2014 |
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COPD Intrabdominal adiposity Body composition Triglycerides Cholesterol |
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Lung Diseases Lung Diseases, Obstructive Pulmonary Disease, Chronic Obstructive Metabolic Syndrome Obesity Respiratory Tract Diseases Insulin Resistance |
Hyperinsulinism Glucose Metabolism Disorders Metabolic Diseases Overnutrition Nutrition Disorders Overweight Body Weight |