This study will randomize children who have difficulty maintaining a healthy weight to one of two treatment groups: lifestyle therapy plus lisdexamfetamine or lifestyle therapy plus placebo.

This pilot study will enroll up to 40 children aged 6 to 12 years who have severe obesity. Individuals will be randomized to receive lifestyle therapy plus lisdexamfetamine or lifestyle therapy plus placebo. Participants will receive therapy for 24 weeks.

Inclusion Criteria:

• Children ages 6 to <12 years at study entry
• Severe obesity defined as BMI >/= 1.2 times the 95th percentile at the screening visit
• Prior failed attempt of lifestyle therapy per parent/guardian report
• Written informed consent of parent/legal guardian and written assent of participant

Exclusion Criteria:

• Contraindications to lisdexamfetamine, including current or recent (< 14 days) use of monoamine oxidase inhibitor and known hypersensitivity to amphetamine products
• Family history of sudden death or ventricular arrhythmia in any first or second degree relative with any of the following: sudden or unexplained death including sudden infant death syndrome, cardiomyopathy, heart transplant, familial arrhythmia (such as Wolff-Parkinson-White syndrome, long QT interval, or implantable defibrillator).
• Any history of fainting or seizure from exercise, startle, or fright
• Clinically significant congenital or structural heart disease or arrhythmia
• BMI <1.2 times the 95th percentile at the baseline/randomization visits
• Hypertension defined as systolic blood pressure (SBP) and/or diastolic blood pressure (DBP) >/= 95th percentile (on 3 separate occasions) at the screening OR baseline/randomization visits
• Tachycardia defined heart rate (HR) >/= 120 bpm (on 3 separate occasions) at the screening OR baseline/randomization visits
• Current or recent (< 3 months) use of psychostimulant or sympathomimetic amine
• History of chemical dependency
• Diabetes mellitus (type 1 or 2)
• Current or recent (< 3 months) use of anti-obesity medication(s)
• Previous bariatric surgery
• Recent initiation or change in dose (< 3 months prior) of anti-hypertensive or lipid medication(s)
• Thyroid stimulating hormone (TSH) > 1.5x upper limit of normal (ULN)
• Aspartate transaminase (AST) or alanine transaminase (ALT) > 3x ULN
• Fasting glucose >/= 126 mg/dL
• History of mania, schizophrenia, bipolar disorder, or psychosis
• Unstable depression or anxiety that has required hospitalization in the past 12 months
• Any history of suicide attempt
• Columbia Suicide Severity Rating Scale (C-SSRS) with a score of Moderate or Hiogh at the screening or baseline/randomization visits
• Children's Depressive Inventory 2 (CDE-2_ score >/= 70 (based on parent or child report) at the screening or baseline/randomization visits
• Concomitant use of tricyclic antidepressants, selective serotonin re-uptake inhibitors (SSRIs), serotonin and norepinephrine re-uptake inhibitors (SNRIs), lithium, fentanyl, tramadol, triptans, tryptophan, buspirone and St. John's wort at any time during the study
• Refusal to use adequate contraception (double barrier method or stable hormonal contraception plus single barrier method, tubal ligation, or abstinence) in girls of childbearing potential
• Inability to swallow test capsule (participants will have two opportunities)