EAL

PWM: Adjunct Therapies (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To evaluate the efficacy of orlistat as an adjunct to diet and exercise therapy for weight loss in obese adolescents.

Inclusion Criteria:

Included if:

between the ages of 14 and 18 years old
had a BMI that exceeded the 85th percentile for age and sex

Exclusion Criteria:

Excluded if:

known secondary causes for obesity such as hypothyroidism
daily corticosteroid exposure for longer than 30 days or history of significant exposure to corticosteroids for chronic illness during the past year
genetic causes of obesity
pregnant (pregnancy test performed on all female subjects each month)

Description of Study Protocol:

Recruitment --recruited from pediatricians in private practice and by newspaper advertisement

Design -- randomized, double-blind, placebo-controlled trial

Blinding used (if applicable)--double-blinded

Intervention (if applicable)--After inital screening, each subject was admitted and stayed overnight in the research study center for baseline evaluation before randomization to orlistat (120 mg 3 times a day) or placebo (pills appeared identical). After fasting overnight, blood specimens were collected. Dietary and exercise counseling, bioelectrical impedance analysis and quality of life (QOL) questionnaires were completed before discharge from center with medication containing either orlistat or placebo. A daily multivitamin supplement was also provided.

Dietary and Exercise Counseling

Subjects in both orlistat and placebo received identical dietary and exercise counseling.

The goal caloric intake was calculated using the Harris-Benedict equation with ambulating activity factor. For weight loss, 500 calories/day (30% fat) were subtracted.

Participants were encouraged to exercise at least 3 times a week for at least 30 minutes per session.

Subjects met with a dietitian monthly to reinforce diet and exercise plan.

Weekly log sheets were provided to record exercise and dietary behaviors.

Statistical Analysis Descriptive statistics included a means + standard deviation (SD) for baseline chracteristics; means + standard error (SE) for outcome data; repeated-measures ANOVA to evaluate differences between the outcome and laboratory measures with the time points (repeated factor) and 2 study groups (grouping factor); paired t tests for comparison within each group.

Results were calculated for the 34 adolescents who completed the study, but also assessed by using intent-to-treat analysis (N = 40)

Using data from adults, the authors determined that a sample size of 15 subjects per group (orlistat and placebo) would be adequate to detect a mean difference in BMI of 2.0 kg/m² at 6 months with 80% power and alpha = 0.05. In order to allow for a 25% attrition rate, 20 subjects were randomized to each group.

p < 0.05 was considered statistically significant.

Data Collection Summary:

Timing of Measurements

Anthropometrics--BMI assessed on a monthly basis. Methodology not provided. Body fat percent was measured by bioelectrical impedance analysis (BIA) at baseline, 3 months, and 6 months.

Laboratory--At baseline, 3 and 6 months visits, a fasting blood sample was obtained for measurement of serum insulin, glucose, lipid panel, and vitamins , D, and E.

Dietary and exercise-- The subjects returned monthly for dietary and exercise counseling. All subjects completed a 3-day diet record at baseline and 6 months and a 24-hour recall at 3 months and 6 months.

Quality of Life--Quality of life questionnaires were completed at baseline and at 6 months.

Adverse Effects--Participants were screened monthly for adverse effects, particularly gastrointestinal symptoms.

Dependent Variables (changes from baseline to 6 months):

Change in BMI
Changes in weight
Lean body mass
Blood chemistry studies

Independent Variables

Treatment group--orlistat or placebo

Control Variables

gender

Description of Actual Data Sample:

At baseline, no statistically significant differences were noted between the 2 study groups for age, sex, ethnicity, BMI, weight, or BIA

Initial N: baseline--40

Gender	Orlistat (n = 20)	Placebo (n = 20)
Female	12	15
Male	8	5

Attrition (final N): 6-months--34. Final gender breakdown not presented.

Orlistat: 16/20; 80% completed study

Placebo: 18/20; 90% completed study

Age: Orlistat group: 15.8 ± 1.5 y; Placebo group: 15.8 ± 1.4 y

Ethnicity: Only information for Hispanic presented. Orlistat group: 12/20 Hispanic; Placebo group: 13/20 Hispanic.

Other relevant demographics: N/A

Anthropometrics:

Characteristic	Orlistat (mean ± SD)	Placebo (mean ± SD)
Weight, kg	111.1 ± 22.9	114.3 ± 38.4
Body Mass Index	39.2 + 5.3	41.7 ± 11.7
Fat by bioelectrical impedance analysis (BIA)	43.7 ± 2.9	44.2 ± 5.0

Location: General Clinical Research Center (GCRC) at the University of New Mexico Hospital in Albuquerque

Summary of Results:

At 6 Months (End of Study)

Within the 2 groups:
The decrease in BMI within the orlistat group was statistically significant (-1.3 ± 1.6 kg/m²; p = 0.04)
The decrease in BMI within the placebo group was statistically significant (-0.8 ± 3.0 kg/m²; p = 0.02)
However, no statistically significant difference was found between the 2 study groups for decrease in BMI from baseline to 6 months (p = 0.39)
The decrease in weight within each group from baseline to 6 months was not statistically significant (p = 0.13 for the orlistat group and p = 0.09 for the placebo group).
There was not a significant difference in weight loss beween the groups (p = 0.54).
There was a significant decrease in % fat by measured by BIA within both the orlistat and placebo group from baseline to 6 months (p < 0.05) (-2.7 ± 1.4 orlistat vs. -0.9 ± 1.6 placebo).
The decrease in % fat measured by BIA was not statistically different between the groups.
Laboratory measurements did not differ between the 2 groups.
There were no gender differences in outcome measures, nor were differences found between the 2 groups in QOL measures from baseline to 6 months.
In comparison with the placebo group, the orlistat group had more adverse events, primarly gastrointestinal symptoms (i.e., oily spotting, fatty or oily stools, or cramping).

Author Conclusion:

This study hypothesized that orlistat therapy would decrease BMI to a greater extent than would placebo. Although some individual subjects in the orlistat group did have clinically significant decreases in BMI, group analysis showed no significant difference between orlistat and placebo. Both the orlistat and placebo groups had a statistically significant decrease in BMI from baseline to 6 months, suggesting that the dietary and exercise counseling that both groups received was beneficial. Because both groups had a large variance in the change in BMI, further study to investigate which subjects benefit from weight-loss intervention and why is indicated. In this study of obese adolescents, orlistat did not significantly reduce BMI in comparison with placebo at 6 months.

No statistically significant differences were found in laboratory measurements between the 2 study groups. A potential adverse effect of orlistat treatment is a decrease in fat-soluble vitamins. Although vitamin D levels was not statistically different from that in the placebo group, this change was not statistically different from that in the placebo group. Supplementation with fat-soluble vitamins and monitoring of vitamins levels in orlistat-treated patients have been advised until further data on this issue have been published.

Funding Source:

Reviewer Comments:

Potential limitations include:

use of BIA rather than dual-energy x-ray absorptiometry or computed tomography to assess lean body mass; BIA is a less sensitive measure but is less expensive and does not deliver irradiation
small sample size
reasonably short study period (only 6 months)
? generalizability for other age groups and ethnic groups

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?		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.)	N/A
	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?		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?	???
	6.4.	Was the amount of exposure and, if relevant, subject/patient compliance measured?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?	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?	N/A
	7.4.	Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures?	N/A
	7.5.	Was the measurement of effect at an appropriate level of precision?	???
	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?	Yes
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?		Yes
	10.1.	Were sources of funding and investigators' affiliations described?	Yes
	10.2.	Was the study free from apparent conflict of interest?	Yes