ONC: EPA/Omega 3 Fatty Acids (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:

To determine if a fish oil-enriched oral, liquid nutritional supplement (standardized to deliver 1.09 g eicosapentaenoic (EPA) per serving) can reverse weight-loss (produce weight gain) in advanced pancreatic cancer patients.

Inclusion Criteria:

Eligible subjects must:

  • Be a male or female between 18 to 80 years of age
  • Have Histologically confirmed or unequivocal operative or radiological diagnosis of unresectable adenocarcinoma of pancreas
  • Have a life expectancy > 2 months
  • Have a WHO performance status < 2 at enrollment
  • Written, informed consent
  • Evidence of ongoing weight loss

 

Exclusion Criteria:

Patients were ineligible to participate if they:

  • Had received surgery or endoscopic stenting during the previous 4 weeks
  • Had other active medical conditions
  • Had another malignancy
  • Were receiving medication that could profoundly modulate metabolism or weight
  • Pregnancy or lactation
Description of Study Protocol:

Recruitment

  • 20 patients recruited to study
  • None had received radiotherapy or chemotherapy
  • On enrollment, none of the participants were jaundiced, pyrexial, ascitic, severely anemic, had evidence of infection or were taking steroids
  • All patients had adequate pain control
  • Pancreatic enzyme supplements were prescribed if patients had or developed clinically evident steatorrhea

Design

  • Time series with nutrition intervention
  • Study approved by Lothian Ethical Committee
  • Each patient served as his/her own control with measures taken at baseline, 3 weeks, and 7 weeks until death, withdrawal from study, or deterioration of physical condition

Intervention

  • Nutrition intervention of oral, liquid nutritional supplement enriched with fish oil, standardized to deliver 1.09 g eicosapentaenoic (EPA) per serving
  • Subjects instructed to consume 2 servings (cans) per day of nutritional supplement in addition to regular intake (nutritional supplement provided by Ross Products)
  • 2 servings per day provided 610 kcal, 32.2 g protein, 2.2 g EPA, and 0.96 decosahexaenoic acid (DHA)
  • Compliance with nutrition intervention was measured by patient diary and return of labels of cans consumed as well as the plasma fatty acid analysis.

Statistical Analysis

  • Median and interquartile range
  • Analyzed on intention-to-treat basis
  • Paired comparisons with baseline values using Wilcoxon signed rank test.
  • p-value < 0.05 denotes significance
Data Collection Summary:

Timing of Measurements

  • Baseline, 3 weeks, and 7 weeks

At initial visit:

  • Assessment of height, pre-illness weight and duration of weight loss

Dependent Variables

*All variables measured at baseline, 3 weeks, and 7 weeks unless otherwise noted

  1. Weight
  2. Mid-arm muscle circumference (MAMC)
  3. Triceps skin-fold thickness (TSF) - 3 measures performed and mean value recorded
  4. Body composition - total body water values derived using validated equation (Hannan et al, 1995); lean body mass (LBM) calculated 
  5. Dietary intake - baseline and 3 weeks; measured using 3-day food diary
  6. Energy expenditure - baseline and 3 weeks; resting energy expenditure (REE) measured (Falconer et al, 1994) after overnight fast using ventilated hood system
  7. C-reactive protein (CRP)
  8. Plasma phospholipid fatty acid analysis - baseline and 3 weeks
  9. Karnofsky performance status - baseline and 3 weeks and monthly thereafter
  10. Appetite - baseline and 3 weeks and monthly thereafter; measured on numerical scale of 0 to 10 where 0 = absolutely no appetite and 10 = extremely good appetite (Simons et al, 1996)
  11. Survival - recorded from time of diagnosis and study baseline to time of death
  12. Labs were drawn for LFTs, glucose, urea, electrolytes and CBC
  13. History and physical performed

Independent Variables

  • Nutrition intervention with oral, liquid nutritional supplement which provided 610 kcal, 32.2 g protein, 2.2 g EPA, and 0.96 decosahexaenoic acid (DHA) per day

Control Variables

  • N/A
Description of Actual Data Sample:

 

Initial N:

  • 20 participants; 10 males and 10 females

Attrition (final N):

  • 18 available for analysis at 3 weeks (2 patients unavailable for analysis due to disease progression)
  • 13 available for analysis at 7 weeks (5 additional patients unavailable for analysis due to disease progression)
  • Reasons for stopping the supplement during the 7-week study period were:
    • temporary interruption in supply of one patient (after 3 weeks)
    • excessive weight gain in one patient (after 3 weeks)
    • dislike of taste in two patients (after 3 weeks)
    • progression of disease in remainder
  • All 18 patients assessed at 3 weeks were consuming the supplement
  • 12 of 13 patients assessed at 7 weeks were consuming the supplement

Age:

  • Median = 62
  • Range = 51-75

Ethnicity:

  • Not provided

Other demographic variables:

  • Tumor stages:

Stage No. of pts.
II 8
III 3
IV 9

  • Previous treatments

Treatment No of pts.
Chemotherapy 0
Radiation 0
Stenting 8
Surgery 8

  • No clinical evidence of ascites or edema noted for the 7 week study period.

Anthropometrics

  • Baseline Weight = 55.2 kg (48.8-61.2)
  • Baseline BMI = 19.8 kg/m2 (17.8-21.8)
  • Rate of weight change per month pre-intervention = -2.9 kg (-4.4 - -2.2)
  • Percent weight loss from usual body weight (UBW) = 17.9% (15.9-22.8)
  • MAMC = 20.8 cm (18.4-22.4)
  • TSF = 11.1 mm (7.8-15.9)
  • Percent Total body water = 52.9% (51.2-56.1) 
  • LBM = 41.5 kg (38.1-44.8)
  • Fat mass = 14.5 kg (12.8-16.7)

Other Clinical Variables

*Values reported are median (interquartile range)

  • CRP = 10 mg l-1 (<10-27)
  • Karnofsky performance status = 85 (80-90); Score ranges from 10 (moribund) to 100 (normal)
  • Appetite = 5 (3-7); Score ranges from 0 (no appetite) to 10 (excellent appetite)

Location:

  • University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH8 9JA, UK
Summary of Results:

Variables

Three Weeks1

Seven Weeks1

Weight Change (kg)

+1.0 (-0.1 + 2.0)
p = 0.0242

+2.0 (-0.4 + 4.6)
p = 0.0332

MAMC Change (cm)

0 (-0.2 + 0.5)
Not Significant

+0.4 (-0.7 + 1.1)
Not Significant

TSF Change (mm)

0 (-0.2 + 0.4)
Not Significant

-0.2 (-0.5 + 0.5)
Not Significant

% Total body water Change

+0.1 (-0.3 + 1.9)
Not Significant

-0.1 (-0.4 + 1.5)
Not Significant

LBM Change (kg)

+1.0 (+0.6 + 1.4)
p = 0.00642

+1.9 (+1.0 + 3.0)
p = 0.00472

Fat mass Change (kg)

-0.2 (-0.8 + 0.9)
Not Significant

+0.2 (-0.6 + 2.0)
Not Significant

CRP Change (mg/l)

0 (0 + 3)
Not Significant

0 (-5 + 22)
Not Significant

Karnofsky performance status Change3

+10 (0 + 10)
p = 0.00472

+10 (0 + 10)
p = 0.0462

Appetite Change4

+1 (0 + 1)
p = 0.0012

+1 (0 + 1)
Not Significant

Caloric Intake (kcal/d)

1798 (1355-2474)5
p = 0.00162

N/A

REE (kcal/d)

1303 (1188-1470)6
p = 0.182

N/A

REE/kg body weight (kcal/kg/d)

24.0 (20.2-25.8)7
p = 0.0252

N/A

REE/kg LBM (kcal/kg/d)

31.8 (27.7-33.9)8
p = 0.0182

N/A

1 Values are median (interquartile range)
2 p-value for paired comparison with baseline value using Wilcoxon signed rank test
3 Score ranges from 10 (moribund) to 100 (normal)
4 Score ranges from 0 (no appetite) to 10 (excellent appetite)
5 Baseline = 1450 kcal (1048-2043)
6 Baseline = 1339 kcal/kg/day (1159-1448)
7 Baseline = 24.2 kcal/kg/day (23.1-27.7)
8 Baseline = 34.0 kcal/kg/day (29.6-35.6)

 

Consumption of nutritional supplement

  • median 1.9 cans (range 1.2-2 cans/day)

No significant changes in lab values of course of study.

Author Conclusion:
  • This small pilot study suggests that a fish oil-enriched oral, liquid nutritional supplement has the potential to be a safe, effective, anti-cachectic agent vs. conventional nutritional supplements.
  • A randomized, controlled trial is required to confirm the observed anti-cachectic effect, evaluate effect on survival, or any as yet undetected side-effects.
  • Pancreatic cancer patients who were previously losing weight were able to gain weight in this study due to the consumption of a fish oil-containing nutritional supplement
  • Pancreatic cancer patients who continued to lose weight on the study did so at a slower rate than prior to the study
  • Hydration remained stable in this study population (reported as TBW as % of BW)
  • Patients in this study appeared to be gaining lean body mass versus just water weight in terms of weight gain.
  • The increase in Karnofsky performance status could be related to improvements in LBM.
  • TSF and MAMC levels did not change and reflect evidence that protein and fat stores were preserved by the administration of omega-3 fatty acid supplement.
  • Caloric intake improved by 500 kcal/day
  • Appetite improved in the initial stages of the study
  • No toxicities were noted from the supplement
  • Fish-oil supplement may have prevented an increase in C-reactive protein levels
Funding Source:
Reviewer Comments:
  • This is a good preliminary pilot study.
  • This study suggests an EPA-enriched oral, liquid nutritional may halt and/or reverse cancer cachexia.
  • There was no control group so cannot rule out that effects were due to simple increases in intake of calories & protein.
  • A controlled trial is required to confirm these findings.
  • It should be noted that one of the authors, AC Voss, is an employee of Ross Products who supplied the nutritional supplement used in this study
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? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? ???
3. Were study groups comparable? N/A
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) No
  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? N/A
  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? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? No
  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.) No
  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? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  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)? ???
  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? Yes
  9.1. Is there a discussion of findings? Yes
  9.2. Are biases and study limitations identified and discussed? Yes
10. Is bias due to study's funding or sponsorship unlikely? No
  10.1. Were sources of funding and investigators' affiliations described? Yes
  10.2. Was the study free from apparent conflict of interest? No