COPDPhase 2NCT00244192
Effects of Infliximab (Remicade) on Fat Free Mass in Patients With Moderate to Severe COPD Suffering From Cachexia
A Phase 2 study testing infliximab (Remicade) in people with COPD and Cachexia, run by Center for Integrated Rehabilitation and Organ Failure Horn at 1 site in Netherlands.
Trial summary
The purpose of this study is to determine whether infliximab is effective on fat-free mass in the treatment of patients with moderate to severe COPD suffering from cachexia. Read more about this study
- Who is it for?
- Ages 40 to 80 years
- What is being tested?
- infliximab (Remicade)
- How many people
- 16 participants
- Where
- 1 siteNetherlands
- Study dates
- Oct 2003to Dec 2005
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 1. COPD acording GOLD with FEV1/FVC ratio < 70%, and post-bronchodilator FEV1 > 20% but < 80% of predicted and an FEV1 of >500ml.
- 2. Fat Free Mass Index : <17.5 kg/m2 in males, <15 kg/m2 in females. 3. Symptomatic (eg, chronic cough, sputum production, shortness of breath) for at least 2 months 4. >= 40 years of age and ≤ 80 years of age 5. History of >=10 pack years of smoking 6. Men and women of childbearing potential must use adequate birth control measures at least one month prior to screening and for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
- 7. Ability to adhere to the study visit schedule and other protocol requirements 8. Provide signed, written informed consent prior to participation in the study 9. Be adequately immunized against S. pneumoniae. Patients enrolling in the study in autumn and winter months should be immunized against influenza 10. The screening laboratory test results must meet the following criteria:
- Hemoglobin >= 8.5 g/dL
- WBC >= 3.5 x 109/L
- Neutrophils >= 1.5 x 109/L
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- Platelets >= 100 x 109/L
- SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper limit of normal range for the laboratory conducting the test.
- TSH within the normal range of 0.3 to 5 mIU/L. 11. Are considered eligible according to the tuberculosis (TB) eligibility assessment, screening, and early detection of reactivation rules
Who cannot join
- > 11% increase in FEV1 as % of predicted after a fixed dose of bronchodilator (200 µg inhaled salbutamol)
- >12% variation between screening and baseline FEV1 assessments
- FEV1 < 500 ml
- Patients with asthma as main component of their obstructive airways disease
- Moderate or severe exacerbation of COPD within previous 2 months
- History or clinical signs of severe cor pulmonale, or pulmonary hypertension, severe right or left sided cardiac failure, serious arrhythmias, myocardial infarction or cardiac interventions within 6 months of screening.
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- Exclude patients with right-sided heart defects, as defined by any 1 of the following 3 echocardiography criteria:
- Right ventricular size increased, with an inlet diameter of >5cm
- Moderate-to-severe tricuspid valve regurgitation
- Right ventricular (RV)-right atrial (RA) pressure drop of >50 mmHg Exclusion of patients with left ventricular ejection fraction (LV EF) of <40%, as measured on echocardiography.
- Exclude patients with the following arrhythmias identified on electrocardiography (ECG):
- Fast atrial fibrillation at ventricular rate of >90/min
- Atrial-ventricular conduction delay of grade 2 or higher : excludes 2nd and 3rd degree heart block.
- Left bundle branch block, with QRS complex >120msec.
- Ventricular arrhythmias: ventricular tachycardia and trigeminy.
- 7. Chronic respiratory failure (PaO2 < 7.3kPa with or without hypercapnia) and patients requiring long term oxygen therapy.
- 8. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to screening or planned participation in pulmonary rehabilitation during the study 9. Stopping smoking or attending a smoking cessation class within 6 weeks of enrollment.
- 10. Known a1 antitrypsin deficiency 11. Serious acute infections (eg, hepatitis, pneumonia or pyelonephritis) in the previous 3 months 12. Major surgery in the previous 3 months 13. Women who are pregnant, nursing, or planning pregnancy within one year after screening (i.e., approximately 6 months following last infusion) 14. Use of any investigational drug within 1 month prior to screening or within 5 half?lives of the investigational agent, whichever is longer 15. Treatment with any other therapeutic agent targeted at reducing TNFa (e.g. pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening. Treatment with immunosuppressive or cytotoxic therapy.
- 16. Previous administration of infliximab 17. Known allergy to murine products 18. Are considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section 4.3.
- 19. Have or have had an opportunistic infection (eg, herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months prior to screening.
- 20. Have a chest radiograph at screening that shows evidence of malignancy, infection, or any abnormalities suggestive of TB 21. Have had an opportunistic infection (e.g. herpes zoster [shingles], cytomegalovirus, Pneumocystis carinii, aspergillosis, histoplasmosis, or mycobacteria other than TB) within 6 months of screening.
- 22. Documented HIV infection. 23. Positive serology for active hepatitis B or C based on all subjects being tested at screening. A positive result will indicate referral to a consultant Hepatologist for further investigation and support.
- 24. Have current signs or symptoms of severe, progressive or uncontrolled renal, hepatic, hematological, gastrointestinal, endocrine, cardiac, neurologic, or cerebral disease (including demyelinating diseases such as multiple sclerosis) 25. Presence of a transplanted organ (with the exception of a corneal transplant > 3 months prior to screening) 26. Malignancy within the past 5 years (except for squamous or basal cell carcinoma of the skin that has been treated with no evidence of recurrence) 27. History of lymphoproliferative disease including lymphoma, or signs and symptoms suggestive of possible lymphoproliferative disease, such as lymphadenopathy of unusual size or location (such as nodes in the posterior triangle of the neck, infra?clavicular, epitrochlear, or periaortic areas), or splenomegaly 28. Known recent substance abuse (drug or alcohol) 29. Poor tolerability of venipuncture or lack of adequate venous access for required blood sampling during the study period 30. Known atypical mycobacterium infection
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Center for Integrated Rehabilitation and Organ failure (CIRO) Horn
Horn, 6085 NM
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Effects of Infliximab (Remicade) on Fat Free Mass in Patients With Moderate to Severe COPD Suffering From Cachexia
The purpose of this study is to determine whether infliximab is effective on fat-free mass in the treatment of patients with moderate to severe COPD suffering from cachexia.
Read the detailed description
COPD is a multicomponent disease characterized by abnormal inflammatory response of the lungs to noxious particles that accompanied by systemic effects like weight loss, muscle wasting, reduced functional capacity and health status. A persistent systemic inflammatory response reflected by enhanced levels of acute phase proteins like C-reactive protein (CRP) or pro-inflammatory cytokines such as tumor necrosis factor (TNF) - α, is present in COPD. There are several studies that indicate that an increased systemic inflammator response is associated with weight loss, cachexia (loss of fat-free muscle mass), physical functioning and health status.
Cachexia associated with systemivc inflammation can not always readily be overcome by nutritional intervention alone.
The hypothesis of this study is that infliximab therapy (3 infusions with 5 mg/kg infliximab or placebo 1:1 on week 0, 2 and 6) will increase fat-free mass relatively to placebo by decreasing inflammation. Secondary endpoints are: lung function, muscle function, exercise capacity and health status. On week 8, 12 and 26 follow-up measurements will be done.
- Being tested
- infliximab (Remicade)
- Keywords
- COPD, infliximab, Remicade, inflammation, cachexia, fat-free mass, health status, exercise capacity
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive, Cachexia, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
infliximab (Remicade)Drug
What is being measured
The primary outcome is the main question the study is designed to answer.
Fat-free mass
Secondary outcomes (16)
Major Secondary Efficacy Endpoints in order of importance:
a. Change in body weight at 8 weeks
b. Change from baseline in functional capacity assessed by the incremental shuttle walk test (ISWT) at 8 weeks
c. Change from baseline in muscle strength (quadriceps, sniff nasal pressure, hand grip strength) at 8 weeks
d. Change from baseline in St George's Respiratory Disease Questionnaire (SGRQ) at 8 weeks
Other Secondary Efficacy Endpoints:
change from baseline at 8 weeks and other timepoints in:
a. Fat-Free Mass (FFM) as measured by DEXA scan
b. Body Mass Index (BMI)
c. Spirometry (FEV1, FVC, PEF25-75)
d. Quality of life as measured by the Short-Form 36-Item (SF-36)
e. Transitional Dyspnoea Index (TDI)
f. Muscle cell histology: muscle biopsy is optional
g. Sputum inflammatory cell count: sputum induction is optional
h. Exacerbation frequency and severity
Other objectives of this trial are to evaluate pharmacokinetics (PK) and pharmacodynamics (PD) in the treatment of patients with COPD-related cachexia.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2005 (estimated)
- Study startOct 2003
- Study completionDec 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for COPDStudies of the same condition, open and under way.
- 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
- Double blind
- Enrolment
- 16 participants
Sponsor and investigators
- Lead sponsor
- Center for Integrated Rehabilitation and Organ Failure Horn
- Sponsor type
- University, hospital or other
- Collaborators
- Centocor, Inc.
- Investigators
- Emiel FM Wouters, PhD, MD, Principal investigator, University Hospital Maastricht, Department of Respiratory Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00244192
- Sponsor's protocol ID
- EU-073
- Status last verified
- Oct 2005
- First submitted
- 25 Oct 2005
- Last updated
- 9 Dec 2005
- Results posted
- No
Publications
van der Vaart H, Koeter GH, Postma DS, Kauffman HF, ten Hacken NH. First study of infliximab treatment in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Aug 15;172(4):465-9. doi: 10.1164/rccm.200501-147OC. Epub 2005 Jun 3.
PubMed 15937294
Study at a glance
From the registry record, last updated by the sponsor on 9 Dec 2005. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Effects of Infliximab (Remicade) on Fat Free Mass in Patients With Moderate to Severe COPD Suffering From Cachexia
- ClinicalTrials.gov ID
- NCT00244192
- Acronym / sponsor ID
- EU-073
- Keywords
- COPD, infliximab, Remicade, inflammation, cachexia, fat-free mass, health status, exercise capacity
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants
- Lead sponsor
- Center for Integrated Rehabilitation and Organ Failure HornUniversity, hospital or other
- Collaborators
- Centocor, Inc.
- Study start
- Oct 2003
- Study completion
- Dec 2005
- First posted
- 26 Oct 2005 (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 infliximab is effective on fat-free mass in the treatment of patients with moderate to severe COPD suffering from cachexia.
Detailed description
COPD is a multicomponent disease characterized by abnormal inflammatory response of the lungs to noxious particles that accompanied by systemic effects like weight loss, muscle wasting, reduced functional capacity and health status. A persistent systemic inflammatory response reflected by enhanced levels of acute phase proteins like C-reactive protein (CRP) or pro-inflammatory cytokines such as tumor necrosis factor (TNF) - α, is present in COPD. There are several studies that indicate that an increased systemic inflammator response is associated with weight loss, cachexia (loss of fat-free muscle mass), physical functioning and health status.
Cachexia associated with systemivc inflammation can not always readily be overcome by nutritional intervention alone.
The hypothesis of this study is that infliximab therapy (3 infusions with 5 mg/kg infliximab or placebo 1:1 on week 0, 2 and 6) will increase fat-free mass relatively to placebo by decreasing inflammation. Secondary endpoints are: lung function, muscle function, exercise capacity and health status. On week 8, 12 and 26 follow-up measurements will be done.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 40 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- 1. COPD acording GOLD with FEV1/FVC ratio < 70%, and post-bronchodilator FEV1 > 20% but < 80% of predicted and an FEV1 of >500ml.
- 2. Fat Free Mass Index : <17.5 kg/m2 in males, <15 kg/m2 in females. 3. Symptomatic (eg, chronic cough, sputum production, shortness of breath) for at least 2 months 4. >= 40 years of age and ≤ 80 years of age 5. History of >=10 pack years of smoking 6. Men and women of childbearing potential must use adequate birth control measures at least one month prior to screening and for the duration of the study and should continue such precautions for 6 months after receiving the last infusion.
- 7. Ability to adhere to the study visit schedule and other protocol requirements 8. Provide signed, written informed consent prior to participation in the study 9. Be adequately immunized against S. pneumoniae. Patients enrolling in the study in autumn and winter months should be immunized against influenza 10. The screening laboratory test results must meet the following criteria:
- Hemoglobin >= 8.5 g/dL
- WBC >= 3.5 x 109/L
Key exclusion criteria (23 listed)
- Exclude patients with right-sided heart defects, as defined by any 1 of the following 3 echocardiography criteria:
- 7. Chronic respiratory failure (PaO2 < 7.3kPa with or without hypercapnia) and patients requiring long term oxygen therapy.
- 8. Participation in the acute phase of a pulmonary rehabilitation program within 4 weeks prior to screening or planned participation in pulmonary rehabilitation during the study 9. Stopping smoking or attending a smoking cessation class within 6 weeks of enrollment.
- 10. Known a1 antitrypsin deficiency 11. Serious acute infections (eg, hepatitis, pneumonia or pyelonephritis) in the previous 3 months 12. Major surgery in the previous 3 months 13. Women who are pregnant, nursing, or planning pregnancy within one year after screening (i.e., approximately 6 months following last infusion) 14. Use of any investigational drug within 1 month prior to screening or within 5 half?lives of the investigational agent, whichever is longer 15. Treatment with any other therapeutic agent targeted at reducing TNFa (e.g. pentoxifylline, thalidomide, etanercept, etc.) within 3 months of screening. Treatment with immunosuppressive or cytotoxic therapy.
- 16. Previous administration of infliximab 17. Known allergy to murine products 18. Are considered ineligible according to the TB eligibility assessment, screening, and early detection of reactivation rules defined in Section 4.3.
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 |
|---|---|---|
| infliximab (Remicade) | Drug | – |
Primary outcome
Fat-free mass
16 secondary outcomes
Major Secondary Efficacy Endpoints in order of importance:
a. Change in body weight at 8 weeks
b. Change from baseline in functional capacity assessed by the incremental shuttle walk test (ISWT) at 8 weeks
c. Change from baseline in muscle strength (quadriceps, sniff nasal pressure, hand grip strength) at 8 weeks
d. Change from baseline in St George's Respiratory Disease Questionnaire (SGRQ) at 8 weeks
Other Secondary Efficacy Endpoints:
change from baseline at 8 weeks and other timepoints in:
a. Fat-Free Mass (FFM) as measured by DEXA scan
b. Body Mass Index (BMI)
c. Spirometry (FEV1, FVC, PEF25-75)
d. Quality of life as measured by the Short-Form 36-Item (SF-36)
e. Transitional Dyspnoea Index (TDI)
f. Muscle cell histology: muscle biopsy is optional
g. Sputum inflammatory cell count: sputum induction is optional
h. Exacerbation frequency and severity
Other objectives of this trial are to evaluate pharmacokinetics (PK) and pharmacodynamics (PD) in the treatment of patients with COPD-related cachexia.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Dec 2005.
- Background: PubMed 15937294van der Vaart H, Koeter GH, Postma DS, Kauffman HF, ten Hacken NH. First study of infliximab treatment in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med. 2005 Aug 15;172(4):465-9. doi: 10.1164/rccm.200501-147OC. Epub 2005 Jun 3.
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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.
Emiel FM Wouters, PhD, MD principal investigator
University Hospital Maastricht, Department of Respiratory Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing infliximab (Remicade) in people with COPD and Cachexia, run by Center for Integrated Rehabilitation and Organ Failure Horn at 1 site in Netherlands.
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 23 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: finished, as of the sponsor's last update on 9 Dec 2005. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. 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. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Fat-free mass. 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 NCT00244192, which also lists 1 linked publication.
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 9 Dec 2005.