COPD: Effectiveness of Therapies (2007-2008)

Citation:

Schols AM, Soeters PB, Mostert R, Pluymers RJ, Wouters EF.  Physiologic effects of nutritional support and anabolic steroids in patients with chronic obstructive pulmonary disease.  A placebo-controlled randomized trial.  Am J Respir Crit Care Med 1995;152(4 Pt 1):1268-74.

PubMed ID: 7551381
 
Study Design:
Randomized Controlled Trial
Class:
A - Click here for explanation of classification scheme.
Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
To assess the effect of a daily nutritional supplement alone or combined with nandrolone decanoate on body composition, lung function, respiratory muscle strength and exercise performance in depleted and non-depleted patients with COPD.
Inclusion Criteria:
  • Patients with moderate to severe COPD consecutively admitted to an intensive inpatient pulmonary rehab program
  • Patients who had an acute exacerbation during the study and who were effectively treated with a short course of glucocorticosteroids and/or antibiotics remained in the study
Exclusion Criteria:
  • Patients who demonstrated an increase in FEV1 > 10% of the predicted baseline value after administration of a bronchodilating agonist (400 ug salbutamol)
  • Unstable COPD
  • Obesity
  • Malignancies
  • Ischemic heart disease or other cardiac impairment
  • Renal, hepatic, gastrointestinal or endocrine diseases
  • History of recent (< 2 months) surgery
Description of Study Protocol:

Recruitment

Consecutive patients admitted to an intensive inpatient pulmonary rehabilitation program.  All patients were referred to the rehab center by their pulmonary physician in a stable clinical condition.

Design:  Randomized Placebo-Controlled Trial.  Patients were stratified into 2 groups according to severity of weight loss and muscle wasting.

Blinding used (if applicable):  Double-blind except for nutritional supplementation

Intervention (if applicable)

  • Randomly allocated to 1 of 3 groups:  Patients receiving placebo nandrolone decanoate treatment, patients receiving placebo nandrolone decanote treatment and supplemental nutrition, and pateints receiving nandrolone decanoate treatment and supplemental nutrition
  • Nutritional intervention (420 kcal, 200 ml daily, 51% fat, 35% carbohydrate, 14% protein) alone for 8 weeks or combined with the anabolic steroid nandrolone decanoate (women, 25 mg; men, 50 mg) or placebo injected on days 1, 15, 29 and 43
  • Exercise program

Statistical Analysis

ANCOVA was done for each of investigated target parameters.  To assess treatment effects, pairwise treatment contrasts along with confidence intervals were calculated.  Pairwise comparisons of the treatment groups were performed by means of Wilcoxon's Rank Sum Test.  Within-group comparisons were performed by Student's t test or Wilcoxon's test when appropriate.  Intention to treat analysis comprised 217 patients and 203 were included in the analysis.

Data Collection Summary:

Timing of Measurements

Measurements of body weight, body composition, serum proteins, dietary intake, lung function, and exercise performance were performed on entry to the study, on Day 29 and on Day 57.

Dependent Variables

  • Body weight
  • Right upper arm circumference
  • Skinfolds measured with skinfold caliper at bicipital, tricipital, subscapular and suprailiac
  • Fat free mass measured through bioelectrical impedance analysis
  • Muscle mass estimated from creatinine height index
  • Serum concentrations of albumin, prealbumin and transferrin were analyzed by radial immunodiffusion
  • Dietary intake measured using diet history method with cross check
  • Resting energy expenditure was measured through indirect calorimetry
  • FEV1 and inspiratory vital capacity were measured with spirometry
  • Arterial blood gases and arterial oxygen and carbon dioxide tension were analyzed on a blood gas analyzer
  • Respiratory muscle strength measured as mouth pressure during maximal static inspiratory maneuvers from RV
  • Exercise peformance evaluated with 12 minute walk 100 m long
  • Side effects of anabolic steroids checked 

Independent Variables

  • Randomly allocated to 1 of 3 groups:  Patients receiving placebo nandrolone decanoate treatment, patients receiving placebo nandrolone decanote treatment and supplemental nutrition, and pateints receiving nandrolone decanoate treatment and supplemental nutrition
  • Nutritional intervention (420 kcal, 200 ml daily, 51% fat, 35% carbohydrate, 14% protein) alone for 8 weeks or combined with the anabolic steroid nandrolone decanoate (women, 25 mg; men, 50 mg) or placebo injected on days 1, 15, 29 and 43
  • Exercise program

Control Variables

 

Description of Actual Data Sample:

Initial N: 233 patients with COPD, gender not mentioned

Attrition (final N):  217 completed the study on an intent-to-treat basis, 203 were included in the efficacy-evaluable analysis

Age:  not mentioned

Ethnicity:  not mentioned

Other relevant demographics:

Anthropometrics:  characteristics between groups not described

Location:  The Netherlands

 

Summary of Results:

Changes in the Nondepleted Patients

 

Placebo (n=38)

Nutrition (n=33)

Nutrition + Anabolic Steroids (n=32)

Weight at baseline, kg 73.7 +/- 8.3

70.5 +/- 5.9

67.9 +/- 8.9

Weight after treatment, kg

73.3 +/- 8.0

71.6 +/- 6.0

69.1 +/- 8.6

Mean change in weight, kg -0.4 +/- 2.4 1.1 +/- 2.4, p < 0.05 1.2 +/- 2.7, P < 0.05
Mean change in FFM, kg -0.2 +/- 2.1 0.5 +/- 3.1 1.4 +/- 2.6, P < 0.05
Mean change in percentage of FFM, % 0.0 +/- 2.9 -0.4 +/- 2.9 0.6 +/- 2.7
Mean change in percentage of subcutaneously assessed fat mass, % -0.2 +/- 2.2 -0.4 +/- 2.2 -0.6 +/- 2.1, P < 0.05
Mean change in creatinine height index, % -4.8 +/- 25.6 4.9 +/- 25.7 6.9 +/- 23.3
Mean change in midarm muscle circumference, cm -0.1 +/- 1.8 0.4 +/- 1.7 0.7 +/- 1.4, P < 0.01

Mean change in maximal inspiratory mouth pressure, kPa

0.5 +/- 1.5

0.8 +/- 1.4, p < 0.01

10.2 +/- 1.9, P < 0.01

Other Findings

In the depleted patients, both treatment regimens induced a similar significant body weight gain (2.6 kg) but different body compositional changes.

Particularly in the last 4 weeks of treatment, weight gain in the nutrition intervention alone group was predominantly due to an expansion of fat free mass (p < 0.03 versus placebo and nandrolone decanoate), whereas the relative changes in fat free mass and other measures of muscle mass were more favorable in the nandrolone decanoate group (p < 0.03 versus placebo).

Maximal inspiratory mouth pressure improved within both treatment groups in the first 4 weeks of treatment, but after 8 weeks only the nandrolone decanoate group was significantly different from placebo (p < 0.03). 

Author Conclusion:
In conclusion, this study shows that nutritional support, as an integrated part of a pulmonary rehabilitation program, can restore energy balance and induce weight gain in depleted patients with COPD.  The results further suggest that supportive treatment with nandrolone decanoate specifically induces an increase in muscle mass even in nondepleted patients.  The preferential increase in muscle mass in depleted patients was found to result in increased respiratory muscle strength.  Because treatment of respiratory muscle weakness directly intervened in a reversible pathophysiologic component of the functional impairment manifested by the Pimax, the presented treatment approach provides new perspectives to improve the functional capacity of patients with COPD.
Funding Source:
Reviewer Comments:
Subject characteristics not described, baseline characteristics between groups not compared.
Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
 
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? Yes
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? Yes
  1.3. Were the target population and setting specified? Yes
2. Was the selection of study subjects/patients free from bias? ???
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? Yes
  2.2. Were criteria applied equally to all study groups? Yes
  2.3. Were health, demographics, and other characteristics of subjects described? No
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? ???
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) ???
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? ???
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) Yes
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? Yes
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) Yes
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? Yes
  4.4. Were reasons for withdrawals similar across groups? Yes
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? Yes
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? Yes
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) Yes
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? Yes
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? Yes
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? Yes
  6.6. Were extra or unplanned treatments described? Yes
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? Yes
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? Yes
  7.1. Were primary and secondary endpoints described and relevant to the question? Yes
  7.2. Were nutrition measures appropriate to question and outcomes of concern? Yes
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? Yes
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? Yes
  7.5. Was the measurement of effect at an appropriate level of precision? Yes
  7.6. Were other factors accounted for (measured) that could affect outcomes? Yes
  7.7. Were the measurements conducted consistently across groups? Yes
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? Yes
  8.2. Were correct statistical tests used and assumptions of test not violated? Yes
  8.3. Were statistics reported with levels of significance and/or confidence intervals? Yes
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? Yes
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? Yes
  8.6. Was clinical significance as well as statistical significance reported? Yes
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? ???
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? No
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? Yes