Chronic Obstructive Pulmonary DiseasePhase 2RAMBONCT01701934
Impact of Roflumilast on Visceral Adiposity and Metabolic Profile in Chronic Obstructive Pulmonary Disease
A Phase 2 study testing Roflumilast in people with Chronic Obstructive Pulmonary Disease and Metabolic Syndrome, run by Laval University at 5 sites in Canada.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 40 to 80 years, men only
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease, Metabolic Syndrome
- What is being tested?
- Roflumilast
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 5 sitesCanada
- Study dates
- Feb 2013to Dec 2014
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 80 years
- Men only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
Canada5 sites
Centre hospitalier de l'Université de Montréal
Montreal, Quebec, H2W 1T8
Montreal Chest Institute
Montreal, Quebec, H2X 2P4
Institut universitaire de cardiologie et de pneumologie de Québec
Québec, Quebec, G1V 4G5
Hôpital régional de Saint-Jérôme
Saint-Jérôme, Quebec, J7Z 5T3
St. Paul's Hospital
Vancouver, British Columbia, V6Z 1Y6
About this study
Official title: 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).
Read the 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.
- Being tested
- Roflumilast, Placebo
- Keywords
- COPD, Intrabdominal adiposity, Body composition, Triglycerides, Cholesterol
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Metabolic Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RoflumilastDrug
Also called DAXAS
500 mcg, oral, once daily for 6 months
PlaceboDrug
Also called Inactive comparator
One placebo pill daily, for 6 months
| Study group | Role | What they receive |
|---|---|---|
| Roflumilast | Experimental | Roflumilast 500 mcg, once daily for 6 months Receives: Drug: Roflumilast |
| Placebo pill | Placebo comparator | Placebo pill, once daily for 6 months Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in intrabdominal adiposity
Measured by CT scan.
Measured: At baseline and 6 months later
Secondary outcomes (7)
Change in body mass index
Measured: At baseline and 6 months later
Change in waist circumference
Measured: At baseline and 6 months later
Change in waist-to-hip circumference ratio
Measured: At baseline and 6 months later
Change in blood metabolic profile
Blood glucose, insulin, triglycerides, apolipoprotein B, LDL/HDL cholesterol, C-reactive protein will be measured.
Measured: At baseline and 6 months later
Change in body composition
As measured by dual-energy X-ray absorptiometry (DEXA).
Measured: At baseline and 6 months later
Change in subcutaneous adiposity
As measured by CT scan.
Measured: At baseline and 6 months later
Change in liver fat
As measured by CT scan
Measured: At baseline and 6 months later
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Oct 2012 (estimated)
- Study startFeb 2013
- Primary completionOct 2014
- Study completionDec 2014 (estimated)
Why it stopped: The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by Laval UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Laval University
- Sponsor type
- University, hospital or other
- Collaborators
- Innovair, Takeda
- Responsible party
- Sponsor
- Investigators
- François Maltais, MD, Principal investigator, Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01701934
- Sponsor's protocol ID
- RAMBO
- Acronym
- RAMBO
- Status last verified
- Nov 2014
- First submitted
- 3 Oct 2012
- Last updated
- 11 Nov 2014
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Sava F, Laviolette L, Bernard S, Breton MJ, Bourbeau J, Maltais F. The impact of obesity on walking and cycling performance and response to pulmonary rehabilitation in COPD. BMC Pulm Med. 2010 Nov 6;10:55. doi: 10.1186/1471-2466-10-55.
PubMed 21054892Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006 Dec 14;444(7121):881-7. doi: 10.1038/nature05488.
PubMed 17167477Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation. 2003 Mar 25;107(11):1514-9. doi: 10.1161/01.cir.0000056767.69054.b3.
PubMed 12654609Marquis K, Maltais F, Duguay V, Bezeau AM, LeBlanc P, Jobin J, Poirier P. The metabolic syndrome in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil. 2005 Jul-Aug;25(4):226-32; discussion 233-4. doi: 10.1097/00008483-200507000-00010.
PubMed 16056071Lam KB, Jordan RE, Jiang CQ, Thomas GN, Miller MR, Zhang WS, Lam TH, Cheng KK, Adab P. Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study. Eur Respir J. 2010 Feb;35(2):317-23. doi: 10.1183/09031936.00024709. Epub 2009 Jul 2.
PubMed 19574332Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):695-703. doi: 10.1016/S0140-6736(09)61252-6.
PubMed 19716961Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):685-94. doi: 10.1016/S0140-6736(09)61255-1.
PubMed 19716960
Study at a glance
From the registry record, last updated by the sponsor on 11 Nov 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Roflumilast on Visceral Adiposity and MetaBolic Profile in Chronic Obstructive Lung Disease: a Randomized and Controlled Trial: the RAMBO Trial.
- ClinicalTrials.gov ID
- NCT01701934
- Acronym / sponsor ID
- RAMBO / RAMBO
- Keywords
- COPD, Intrabdominal adiposity, Body composition, Triglycerides, Cholesterol
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Laval UniversityUniversity, hospital or other
- Collaborators
- Innovair, Takeda
- Study start
- Feb 2013
- Primary completion
- Oct 2014 (actual)
- Study completion
- Dec 2014 (estimated)
- First posted
- 5 Oct 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Roflumilast | Experimental | Drug: RoflumilastRoflumilast 500 mcg, once daily for 6 months |
| Placebo pill | Placebo comparator | Drug: PlaceboPlacebo pill, once daily for 6 months |
Who may qualify
- Ages
- 40 to 80 years
- Sex
- Male only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 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
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RoflumilastAlso: DAXAS500 mcg, oral, once daily for 6 months | Drug | Roflumilast |
| PlaceboAlso: Inactive comparatorOne placebo pill daily, for 6 months | Drug | Placebo pill |
Primary outcome
Change in intrabdominal adiposity
Time frame: At baseline and 6 months later
Measured by CT scan.
7 secondary outcomes
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
Change in body composition
Time frame: At baseline and 6 months later
Change in subcutaneous adiposity
Time frame: At baseline and 6 months later
Change in liver fat
Time frame: At baseline and 6 months later
Results and safety
The study was stopped early (reason given: The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Nov 2014.
- Background: PubMed 21054892Sava F, Laviolette L, Bernard S, Breton MJ, Bourbeau J, Maltais F. The impact of obesity on walking and cycling performance and response to pulmonary rehabilitation in COPD. BMC Pulm Med. 2010 Nov 6;10:55. doi: 10.1186/1471-2466-10-55.
- Background: PubMed 17167477Despres JP, Lemieux I. Abdominal obesity and metabolic syndrome. Nature. 2006 Dec 14;444(7121):881-7. doi: 10.1038/nature05488.
- Background: PubMed 12654609Sin DD, Man SF. Why are patients with chronic obstructive pulmonary disease at increased risk of cardiovascular diseases? The potential role of systemic inflammation in chronic obstructive pulmonary disease. Circulation. 2003 Mar 25;107(11):1514-9. doi: 10.1161/01.cir.0000056767.69054.b3.
- Background: PubMed 16056071Marquis K, Maltais F, Duguay V, Bezeau AM, LeBlanc P, Jobin J, Poirier P. The metabolic syndrome in patients with chronic obstructive pulmonary disease. J Cardiopulm Rehabil. 2005 Jul-Aug;25(4):226-32; discussion 233-4. doi: 10.1097/00008483-200507000-00010.
- Background: PubMed 19574332Lam KB, Jordan RE, Jiang CQ, Thomas GN, Miller MR, Zhang WS, Lam TH, Cheng KK, Adab P. Airflow obstruction and metabolic syndrome: the Guangzhou Biobank Cohort Study. Eur Respir J. 2010 Feb;35(2):317-23. doi: 10.1183/09031936.00024709. Epub 2009 Jul 2.
- Background: PubMed 19716961Fabbri LM, Calverley PM, Izquierdo-Alonso JL, Bundschuh DS, Brose M, Martinez FJ, Rabe KF; M2-127 and M2-128 study groups. Roflumilast in moderate-to-severe chronic obstructive pulmonary disease treated with longacting bronchodilators: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):695-703. doi: 10.1016/S0140-6736(09)61252-6.
- Background: PubMed 19716960Calverley PM, Rabe KF, Goehring UM, Kristiansen S, Fabbri LM, Martinez FJ; M2-124 and M2-125 study groups. Roflumilast in symptomatic chronic obstructive pulmonary disease: two randomised clinical trials. Lancet. 2009 Aug 29;374(9691):685-94. doi: 10.1016/S0140-6736(09)61255-1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
François Maltais, MD principal investigator
Institut universitaire de cardiologie et de pneumologie de Québec, University Laval
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Roflumilast in people with Chronic Obstructive Pulmonary Disease and Metabolic Syndrome, run by Laval University at 5 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 11 Nov 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: The recruitment of the study was prematurely stopped in July 2014 for the following reason; no more study medication.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in intrabdominal adiposity (time frame: At baseline and 6 months later). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01701934, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Nov 2014; AzTrials last refreshed its copy on 8 Nov 2026.