EAL

PWM: Adjunct Therapies (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To describe the authors' experience with weight reduction treatment using sibutramine in adoescents suffering from morbid obesity

Inclusion Criteria:

Female and male adolescents with morbid obesity (BMI >95th percentile for age and/or 30kg/m²) treated at a nutrition clinic of Assaf Harofeh Medical Center, Israel during Nov 2000 and Nov 2001.

Exclusion Criteria:

Subjects could not have disorders that affected metabolism like hypothyroidism, diabetes mellitus, Cushing syndrome, severe hyperlipidemia, known significant hypertension or other cardiovascular disease, psychiatric conditions or specific eating disorders, and participation in other weight control programs within 3 months prior to this intervention.

Description of Study Protocol:

Recruitment

Recruitment strategy not described.

Design

Nonrandomized trial

Blinding used
Neither subjects nor investigators were blinded

Intervention

All subjects had an initial evaluation that included history, physical exam, blood work (complete blood count, electrolytes, urea, creatinine, lipid profile, liver transaminase, TSH, free thyroxine and blood cortisol at 8 am), and psychiatric assessment by a psychiatrist.
Individualized, moderate, balanced calorie-restricted diet with conventional food planned by a pediatric RD, taking into account age, gender, personal preferences and growth potential. Diets for younger adolescents were less restrictive and closer to the recommended daily allowance of calories in order not to impair growth. Adolescents were instructed to consume 1200-1700 calories with 30% from fat, 15% protein, and the remainder from carbohydrates. MVI and calcium supplements were added as needed.
Daily physical activity was encouraged.
10 mg sibutramine daily was initiated at the second clinic visit after the medical and psychiatric assessments were completed.

Statistical Analysis

Results were presented as means and standard deviations.

Paired t-tests were performed to assess the significance of weight reduction at different time points.

Pearson correlation test was used to calculate correlations between weight reduction and age.

Data Collection Summary:

Timing of Measurements

Subjects were evaluated weekly at the nutrition clinic.

Results were presented for 3 months, 6 months and 1 year after enrollment.

Dependent Variables

weight loss
BMI

Independent Variables

Sibutramine

Control Variables

No control variables were described.

Description of Actual Data Sample:

Initial N:

20 subjects with 13 females and 7 males

Attrition (final N):

3 months: N = 13
6 months: N = 7
9 months: N = 6
1 year: N = 3

Age: Mean age: 15 years 4 months (range 13-18 years)

Ethnicity: Not described

Other relevant demographics: Not described

Anthropometrics: mean BMI of group: 40 + 5.6 kg/m² (range 30.1 -49.5 kg/m2)

Location: Nutrition clinic at Assaf Harofeh Medical Center, Israel

Summary of Results:

Analysis of Change in Weight and BMI from Baseline (mean + SD)

Time (mo)	N	Wt Change (kg)	P	BMI Change	P
3	13	6.2 + 4.3	<0.001	2.4 + 1.7	<0.001
6	7	10.8 + 3.7	<0.001	4.4 + 1.7	<0.001
9	6	no info		no info
12	3	13.5 + 5.5	0.051	6.1 + 1.7	<0.05

Other Findings

1. Statistically significant reduction in weight (change = 4.1 + 3.7 kg, P < 0.05) and BMI (change = 1.8 + 1.3, P < 0.01) from 3 to 6 months in 7 subjects.

2. All weight changes over the second six months had no statistical significance.

3. No correlation was found between weight reduction and age.

4. High drop out rate related to slow rate of weight reduction and fear of further disappointment with an unsuccessful weight reduction program.

5. Motivating factors for staying with the treatment longer included academic or army service qualification, peer acceptance and resolution of obesity-related medical problems.

6. Improvement in concomitant disorders

Severe asthma: 2 subjects demonstrated reduced clinical complaints, decreased use of bronchodilator therapy and no hospitalizations compared to frequent admissions prior to study. Lung function tests revealed a 10-15% improvement in expected forced expiratory volume during 1 second, from 65% to 75-80% after weight reduction.
Three patients with blood pressures above the 90th percentile for age, gender and height showed a reduction in the mean arterial pressure from 105, 90-100, to 93, 80-93 mmHG, respectively which are WNL for age, gender and height.
One patient with Down's syndrome, who suffered obstructive sleep apnea and was managed with BiPAP, was able to sleep freely without deoxygenation eisodes and an otolaryngologic surgical procedure was avoided.
Adverse reactions were mild, transient, well tolerated and were not the reason for dropout: constipation (2 subjects), headaches (2 subjects).

Author Conclusion:

Sibutramine may help achieve weight reduction and improvement in concomitant health problems short term but it's long term effect is limited.

Funding Source:

Reviewer Comments:

Subject Characteristics:

The authors did not describe the number of subjects suffering other disorders such as asthma, hypertension, obstructive sleep apnea. Did not describe characteristics of males vs females.
Authors didn't define severe hyperlipidemia, signficant hypertension or cardiovascular disease.

Anthropomentric measurements:

No description of how height and weight were measured

Intervention:

No dietary or physical activity data were presented although all participants were expected to follow lower calorie diet and engage in physical activity. Did subjects achieve recommended calorie and activity levels? How often did the subjects meet with the pediatric dietitian - initially or throughout the study?
For younger adolescents was the goal weight loss or weight maintenance?
Compliance with sibutramine regimen not addressed.
Why did two subjects receive a higher dose of sibutramine and why did one subject stop sibutramine for two months, then restart? If these strategies were offered to all, would retention have been better?
Didn't discuss 9 month time point - increase in weight per Figure 1 in paper

Characteristics of dropouts:

Were older or younger adolescents more likely to dropout?
Females vs males more likely to dropout?

Analysis:

Small sample size initially (N=20) but extremely small at 1 year time point (N=3).
Intention to treat analysis not applied.

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?	No
	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)	Yes
	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?	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?		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.)	N/A
	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?	No
	6.5.	Were co-interventions (e.g., ancillary treatments, other therapies) described?	Yes
	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?	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?		No
	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)?	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?	No
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