COPD, Cachexia
Conditions
Keywords
COPD, infliximab, Remicade, inflammation, cachexia, fat-free mass, health status, exercise capacity
Brief 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.
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.
Interventions
Sponsors
Centocor, Inc.
Center for Integrated Rehabilitation and Organ Failure Horn
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
40 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
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: 1. Hemoglobin \>= 8.5 g/dL 2. WBC \>= 3.5 x 109/L 3. Neutrophils \>= 1.5 x 109/L 4. Platelets \>= 100 x 109/L 5. SGOT (AST) and alkaline phosphatase levels must be within 3 times the upper limit of normal range for the laboratory conducting the test. 6. 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
Exclusion criteria
1. \> 11% increase in FEV1 as % of predicted after a fixed dose of bronchodilator (200 µg inhaled salbutamol) 2. \>12% variation between screening and baseline FEV1 assessments 3. FEV1 \< 500 ml 4. Patients with asthma as main component of their obstructive airways disease 5. Moderate or severe exacerbation of COPD within previous 2 months 6. 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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Fat-free mass | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 | — |
| Major Secondary Efficacy Endpoints in order of importance: | — |
| 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. | — |
| b. Body Mass Index (BMI) | — |
Countries
Netherlands
Outcome results
None listed