NCT00001723.

Methods	Type of trial: interventional, randomised controlled trial Allocation: randomised Intervention model: parallel assignment Masking: double blind (participant, carer, investigator, outcomes assessor) Primary purpose: treatment
Participants	Condition: diabetes mellitus hypertension metabolic disease obesity sleep apnoea syndrome Enrolment: 200 Inclusion criteria: good general health. People taking medications for obesity‐related comorbid conditions not excluded obesity: BMI for age and triceps skinfold > 95th percentile (determined by National Health and Nutrition Examination Survey I age‐, sex‐ and race‐specific data). All participants > 60 kg in bodyweight evidence for a quantifiable obesity‐related comorbidity. Examples include: systolic or diastolic hypertension (determined by age‐specific charts); frank type 2 diabetes, impaired glucose tolerance assessed by OGTT; hyperinsulinaemia (fasting insulin > 15 mIU/mL); significant hyperlipidaemia (total cholesterol > 200 mg/dL, low‐density lipoprotein cholesterol > 129 mg/dL or fasting triglycerides > 200 mg/dL); hepatic steatosis (ALT or AST above normal range with negative hepatitis trials) or sleep apnoea documented by a sleep trial aged 12 to 17 years at the start of the trial for girls with childbearing potential, a negative pregnancy test before taking and while taking trial medication. Sexually active females used an effective form of contraception, including. total abstinence, oral contraceptives, an intrauterine device, levonorgestrel implants or medroxyprogesterone acetate injections. If one of these could not be used, contraceptive foam with a condom race of all 4 grandparents self‐identified as either all Caucasian or all African‐American Exclusion criteria: presence of renal, hepatic (other than obesity‐related steatosis), gastrointestinal, most endocrinological (e.g. Cushing's syndrome), or pulmonary disorders (other than either asthma not requiring continuous medication or sleep apnoea‐related disorders) pregnancy, breastfeeding or having unprotected intercourse had, or had parent or guardians who had, current substance abuse or a psychiatric disorder or other condition which, in the opinion of the investigators, would impede competence or compliance or possibly hinder completion of the trial regularly used prescription medications unrelated to the complications of obesity. Oral contraceptive use permitted, provided the contraceptive was used for at least 2 months before starting trial medication. Use of nonprescription and prescription medications reviewed on a case‐by‐case basis; depending on the medication, participants who have continued to take prescription medication for at least 3 months prior to trial entry were eligible recent use (within 6 months) of anorexiant medications for weight reduction inability to undergo magnetic resonance imaging (e.g. volunteers with metal within their bodies including cardiac pacemakers, neural pacemakers, aneurysmal clips, shrapnel, ocular foreign bodies, cochlear implants, nondetachable electronic or electromechanical devices such as infusion pumps, nerve stimulators, bone growth stimulators, etc. that are contraindications)
Interventions	Intervention: orlistat Comparator: placebo
Outcomes	Primary outcome: change in BMI SDS (baseline to 6 months) Secondary outcomes: change in bodyweight change in BMI change in body fat, body fat distribution measures obtained from DEXA effect of race on change in weight, difference in change of weight according to race (non‐Hispanic white participants versus non‐Hispanic black participants)
Study details	NCT number: NCT00001723 Other trial ID numbers: 980111, 98‐CH‐0111
Publication details	"Safety and Efficacy of Orlistat (Xenical, Hoffmann LaRoche) in African American and Caucasian Children and Adolescents with Obesity‐Related Comorbid Conditions"
Stated aim for study	Quote: "Researchers propose to determine the safety, tolerability, and efficacy of Xenical [orlistat] in 12‐17 year old severely obese African American and Caucasian children and adolescents who have one or more obesity‐related disease (hypertension, hyperlipidemia, sleep apnea, hepatic steatosis, insulin resistance, impaired glucose tolerance, or Type 2 diabetes)"
Notes	The trial was completed when identified. Trial collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Roche Pharma AG Results presented on the clinicaltrials.gov website and in a conference abstract. Results from ClinicalTrials.gov Results Database: change in BMI SDS orlistat: ‐0.12 ± 0.02 and placebo: ‐0.06 ± 0.02. ANCOVA differences between groups P value = 0.007. Change in bodyweight orlistat: ‐2.9 ± 0.7 and placebo: ‐0.6 ± 0.7. No statistical analysis provided. Change in BMI orlistat: ‐1.44 ± 0.26 and placebo: ‐0.50 ± 0.20. No statistical analysis provided. 95/100 participants in orlistat and 94/100 in placebo group experienced adverse events with the most common being gastrointestinal disorders. No serious adverse events in orlistat group. In placebo group, 1 participant had hypoglycaemia and 1 participant had left lower quadrant pain and vomiting, and was admitted to hospital overnight
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Low risk	Quote from author (via email): "We randomized participants in a 1:1 fashion to orlistat 120 mg or identical appearing placebo thrice daily with meals plus a daily multivitamin (Centrum, Whitehall‐Robins Healthcare, Madison, NJ) containing 5000 IU vitamin A (80% as retinol, 20% as beta carotene), 400 IU vitamin D as ergocalciferol, 30 IU vitamin E (as di‐α tocopheryl acetate), and 25 mcg vitamin K (as phytonadione). Investigators assigned consecutive code numbers to participants from pre‐specified lists that were stratified by race (Caucasian versus African American), sex (Male, Female), and degree of pubertal development (3 strata for boys: testes <15ml, testes 15‐20mL, and testes >20mL; for girls: Breast Tanner stage I‐III; Tanner stage IV, and Tanner stage V). The NIH CRC Pharmaceutical Development Section used permuted blocks with stratification to generate allocations that translated code numbers into trial group assignments by using a pseudo‐random number program" Comment: randomisation process described
Allocation concealment (selection bias)	Low risk	Quote from author (via email): "Pharmacy personnel not involved with the conduct of the study, dispensed identical‐appearing study capsules in containers that differed only by participant code number. During the trial, no participant, investigator, or other medical or nursing staff interacting with participants was aware of study group assignments" Comment: allocation was concealed
Blinding of participants and personnel (performance bias) Objective outcomes	Low risk	Quote: "Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)" Comment: participants and personnel were blinded
Blinding of participants and personnel (performance bias) Subjective outcomes	Low risk	Quote: "Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)" Comment: participants and personnel were blinded
Blinding of outcome assessment (detection bias) Objective outcomes	Low risk	Quote: "Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)" Comment: assessors were blinded
Blinding of outcome assessment (detection bias) Subjective outcomes	Low risk	Quote: "Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)" Comment: assessors were blinded
Incomplete outcome data (attrition bias) Objective outcomes	Low risk	Comment: according to ClinicalTrials.gov, 87% of orlistat participants completed the trial, 84% completed placebo arm
Incomplete outcome data (attrition bias) Subjective outcomes	Low risk	Comment: according to ClinicalTrials.gov, 87% of orlistat participants completed the trial, 84% completed placebo arm
Selective reporting (reporting bias)	High risk	Comment: there are differences in the results reported on the ClinicalTrial.gov website and in the conference abstract
Other bias	Unclear risk	Comment: unclear as limited information available