DF: Cardiovascular Disease (2008)

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

To determine the effects of a water soluble fiber supplement on blood lipid levels in a clinic population with mild to moderate hypercholesterolemia.

Inclusion Criteria:
  • Mild to moderate hypercholesterolemia
  • 18 years to 70 years old.
Exclusion Criteria:
  • Clinic attendees with severe hypercholesterolemia
  • Use of hypolipidemic drugs withing the last two months
  • Use of food or food supplements to lower plasma lipids
  • Above 30% ideal body weight.
Description of Study Protocol:

Recruitment

  • Each clinic was asked to enroll at least 20 eligible clinic attendees
  • No special recruitment strategies were used.

Design

Eligible clinic attendees (subjects) were placed on the National Cholestrol Education Program (NCEP) Step 1 Diet for nine weeks, then randomly assignmed to the Control or Experimental Group.

Blinding Used

  • Placebo and fiber packets were identical in appearance and taste
  • Data collectors blinded to outcomes due to objective lab results.

Intervention

  • Subjects were given packets (either containing placebo or fiber) to eat before breakfast and dinner
    • Subjects were instructed to use one packet before dinner throughout the treatment, one packet before breakfast every ohter day during the second week of treatment and one packet before breakfast every day during the remainder of treatment
    • The subjects were instructed to mix the packet with 296ml of skim milk or juice and consume within five minutes.
  • After 15 weeks of the placebo treatment, subjects in the Placebo Group were instructed to use two fiber packets a day (before breakfast and dinner)
  • Packets contain either 10g fiber [15-gram mixture of water soluble fibers (guar gum and pectin), with a five-gram mixture of non-water soluble fibers (pea fiber, soy fiber and corn bran)] or 5.2g placebo (non-water soluble fiber from cellulose)
  • Subjects completed three-day food diaries at baseline and Weeks Eight, 14, 32 and 50. These diaries were analyzed by a dietitian and given a food record rating score. The analysis was used to confirm adherance to the NCEP Step 1 Diet.

Statistical Analysis

  • Statistical analyisis using SAS software
  • Planned sample size of 40 subjects in each treatment group for the 15-week treatment period
  • Analysis of covariance. Covariants: Overall mean, effect of treatment week, sex, pre-treatment age, weight, BMI, Food Record Rating (FRR).
  • Mean LDL-C, HDL-C, triglyercides and TC at baseline, Weeks Six, 12, 15 and end-point at 36 weeks 
  • Proportions compared using Fisher's exact test
  • Two-tailed significance test.
Data Collection Summary:

Timing of Measurements

  • LDL-C and triglycerides
    • Six weeks before start of treatment
    • Three weeks before start of treatment.
  • Apo A-1 and B, serum iron, ferritin, vitamins A and E
    • Baseline
    • Week Six
    • Week 15
    • Every six weeks for the remaining 36 weeks.
  • Total cholesterol (TC), HDL-C, triglycerides
    • Every six weeks for the remaining 36 weeks
    • Baseline
    • Week Three
    • Week Six
    • Week Nine
    • Week 12
    • Week 15.
  • Three-day food Diary
    • Baseline
    • Week Eight
    • Week 14
    • Week 32
    • Week 50.

Dependent Variables

Serum lipid levels

  • Total cholesterol
  • LDL-C
  • LDL-C/HDL-C
  • Triglycerides.

Independent Variables

Fiber: 20g per day (predominately water soluble fiber) "Choltrol," supplied by Novarits Consumer Health.

Control Variables

  • Sex
  • Weight
  • Age
  • BMI
  • Food record rating.
Description of Actual Data Sample:

Initial N

162 (104 males, 58 females)

  • 282 started Step 1 Diet
  • 169 completed nine-week diet stabilization (60%)
  • 162 randomized to treatment groups (attrition of six Fiber subjects and one Placebo subject)
  • Included in Efficacy Analysis: 58 from the Fiber Group, 67 from the Placebo Group
  • 102 completed the 15-week comparative phase: 52 from the Fiber Group, 50 from the Placebo Group
  • 70 completed the 36-week extention phase: 40 from the Fiber Group, 30 from the Placebo Group).

Attrition (Final N)

70 (sex not described)

  • Excluded from the efficacy analysis
    • Less than 80% diet compliant (three in the Fiber Group, four in the Placebo Group)
    • Not compliant with Step 1 Diet (19 in Fiber, 10 in Placebo)
    • Did not complete at least six weeks of treatment (one in the Fiber Group).
  • Withdrew due to GI side effects
    • Fiber Group: Seven
    • Placebo Group: Eight. 
  • Approximately equal numbers of subjects at each study site were excluded from the analyses.

Age

  • Fiber Group: Range, 26 to 69 years; mean, 51.1 years
  • Placebo Group: Range, 29 to 67 years; mean, 53.7 years.

Ethnicity

  • Fiber: 97.5% white
  • Placebo: 91.4% white.

Other Relevant Demographics

65% male, 35% female.

Anthropometrics

  • Fiber: BMI, 25.7±3.3
  • Placebo: BMI, 25.7±3.6.

Location

Multi-center study including states Washington, California, Illinois, Texas, Kansas, Maryland, Minnesota and New Jersey.

Summary of Results:

 15 Week Data: Change in Parameters from Baseline to 15 weeks

Variables

Treatment Group
Mean change

Control Group
Mean change

Statistical Significance of Group Difference

Serum Cholesterol

LDL-C

-0.41±0.36mmol/L
(-9.7%)

0.00±0.41mmol/L
(0%)

P<0.001

TC

-0.44±0.45mmol/L
(-7.0%)

-0.03±0.47mmol/L
(-0.5%)

P<0.001 

LDL-C/HDL-C

-0.25±0.37mmol/L
(-7.9%)

0.06±0.42mmol/L
(1.9%)

P<0.001

Apo B -14.3±21.1g/L
(-10.0%)
3.6±20.5g/L
(2.6%)

P<0.001

  • No significant within treatment decreases in LDL-C, TC, LDL/HDL-C or Apo B
  • No significant differences between Fiber Supplement and Placeo Groups in the mean changes from basline in weight, FRR score, iron, ferritin, vitamins A and E
  • No covariate was statiscally significant.

36-Week Data

Subjects switched from placebo to fiber supplement: Significant decrease in LDL-C, TC and LDL-C/HDL-C.

Other Findings

  • During the 15-week treatment period, there were no significant changes in mean daily cholesterol and fiber consumption based on analyses of the three-day food record
  • No significant differences between pre-treatment characteristics of subject, except mean FRR score for the Fiber Group was higher, indicating a slightly higher level of fat intake (9.9 vs. 8.3; P<0.05)
  • Greatest reduction in LDL-C and TC occurred at Week 12 (13.3% and 8.7%), compared to Week 15 (9.7% and 7.0%).
Author Conclusion:

Fiber supplement provided significant and sustained reductions in LDL-C without reducing HDL-C or increasing triglycerides over 51-week treatment period.

Funding Source:
Reviewer Comments:
  • Missing discussion topics which could assist in explaining outcomes:
    • Discussion of ancillary treatments or co-interventions, including exercise regime
    • Discussion of unplanned or extra treatment.
  • Potential bias: Fiber packet proved by Novartis Pharmaceuticals
  • Crossover study design in the final three weeks of the study, when the Placebo Group switched to fiber-containing packets and experienced a reduction in LDL-C. The reduction was less for the Placebo Group than the Fiber Group that started in the beginning.

 

 

 

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? Yes
  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? Yes
  2.4. Were the subjects/patients a representative sample of the relevant population? Yes
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) Yes
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? Yes
  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? No
  4.1. Were follow-up methods described and the same for all groups? No
  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? ???
  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? N/A
  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? Yes
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? No
  6.6. Were extra or unplanned treatments described? No
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? ???
  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? No
  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)? ???
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? No
  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? ???
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? No
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