PWM: Adjunct Therapies (2006)
- adolescents aged 10 to 16 years
- severe exogenous obesity, defined as weight for height index > 140% in otherwise healthy subjects
Obese adolescents excluded if obesity was associated with or was the result of:
- endocrinopathy
- genetic syndromes
- medications
Recruitment -- Adolescents were recruited among the patients who were referred to study centers (number of centers not discussed) for evaluation and management of exogenous obesity.
Design -- Prospective, randomized, controlled pilot trial
Blinding used (if applicable)--none
Intervention
Randomization was done by alternation of successive patients who met the inclusion criteria to receive orlistat (120 mg three times daily) and a daily multivitamin in addition to conventional treatment or conventional treatment only (control group).
Dietary and Exercise
Both orlistat and control groups received conventional treatment (lifestyle modification) which included reduced-calorie diet and increased physical activity components.
Lifestyle modification program was administered by a team consisting of a pediatric endocrinologist, pediatrician and a dietitian at each study center.
The program included:
- 20% reduction in daily calories calculated for age and sex.
- At least 30 minutes of moderate exercise per day.
Lifestyle modification (diet and exercise) was reinforced at bimonthly clinic visits. Compliance with diet and exercise program was rated as poor, fair, or good.
Monitoring of Adverse Effects
Subjects receiving orlistat were monitored during study about gastrointestinal complaints.
Statistical Analysis --A t-test was used to evaluate differences between the treatment and control groups in parameters examined. The Mann-Whitney rank sum test was used for the parameters that did not follow a Gaussian distribution
p < 0.05 was considered statistically significant.
Timing of Measurements
Height and weight measurements at beginning and end of study in outpatient clinic examinations; protocol not discussed.
Lifestyle modification (diet and exercise) was reinforced at bimonthly clinic visits. Compliance with diet and exercise program was rated as poor, fair, or good.
Gastrointestinal complaints attributed to orlistat were monitored during study duration.
Dependent Variables (changes from baseline to end of trial)
- Changes in weight
- Changes in BMI
- Percent weight change
Independent Variables
- Treatment group--orlistat and conventional treatment or conventional treatment only (control)
Control Variables
Not discussed
Initial N: Orlistat group: N = 22 adolescents; Control group: N = 20 adolescents
Attrition (final N): Orlistat group: N = 15 (7 withdrew from study within 1st month due to adverse gastrointestnal effects of orlistat); Control group: N = 15 (loss to follow-up due to noncompliance with bimonthly clinic examinations)
Age: Orlistat group: 12.9 ± 2.4 y; Control group:12.5 ± 2.2 y
Ethnicity: not presented
Other relevant demographics: Gender: 5 males and 10 females in both groups
Anthropometrics: (at initiation of study)
| Variable | Orlistat Group (mean ± SD) | Control Group (mean ± SD) | P value |
| Weight (kg) | 82.1 ± 20.9 | 73.9 ± 15.3 | NS |
| BMI | 32.5 | 31.2 |
0.018 |
Location: Turkey
Adolescents on orlistat in addition to conventional treatment (N = 15) were followed for 5-15 months (average 11.7 ± 3.7 months).
Adolescents in the control group (conventional treatment only) (N = 15) were followed for 6-17 months (average 10.2 ± 3.7 months)
Over the study period:
|
Variables |
Orlistat Group Mean ± SD |
Control group Mean ± SD |
P value |
|
Change in BMI (initial - final BMI) |
-4.09 ± 2.9 |
0.11 ± 2.49 |
<0.001 |
|
Weight Change (kg) |
-6.27 ± 5.4 |
4.16 ± 6.45 |
<0.001 |
|
Percent Weight Change |
-7.65 ± 6.5 |
5.7 ± 8.3 |
<0.001 |
Two patients in the orlistat group and nine patients in the control group gained weight during the study.
Other Findings
Reported compliance with the diet and exercise program was fair to poor after the first 2 months in both orlistat and control groups.
Mild gastrointestinal complaints were experienced by all orlistat-receiving patients. Seven of the patients in the orlistat group dropped out of the study within the first month due to gastrointestinal side-effects.
"In the current study, we report the results of 15 adolescents who remained on orlistat for an average duration of 11.7 months. We show that weight loss reported by short-term treatment with orlistat (2 studies conducted with pediatric populations--McDuffie JR et al, 2002 and McDuffie JR et al, 2004) is maintained in the medium term in adolescents. BMI decreased significantly in patients of the orlistat group compared to the control group. However, none of the patients was able to achieve a BMI that was normal for age. Control adolescents continued to gain weight and their BMI showed either no change or slight increases, despite efforts of lifestyle interventions."
"Orlistat could be a useful adjunct in the treatment of severe obesity in adolescents, however, gastrointestinal side-effects limit its usefulness to almost one in three adolescents. The true benefit of orlistat remains to be determined in a larger placebo-controlled study."
Limitations of study:
- Fair to poor noncompliance with diet and exercise after first 2 months of study; a more vigorously and frequently monitored lifestyle intervention could have resulted in better outcomes in both groups
- Small sample size in both orlistat and control groups with 32% and 25% attrition rates in the orlistat and control groups, respectively
- Most participants were females (67% in both groups)
- ? generalizability to other age groups
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Quality Criteria Checklist: Primary Research
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| 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? | 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.) | 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? | No | |
| 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? | 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? | 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? | ??? | |
| 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? | ??? | |
| 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)? | No | |
| 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? | Yes | |
| 10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
| 10.2. | Was the study free from apparent conflict of interest? | Yes | |