Phentermine/Topiramate in Children, Adolescents, and Young Adults With Hypothalamic Obesity: a Pilot and Feasibility Study
Hypothalamic obesity (HO) refers to the substantial weight gain that often complicates hypothalamic brain tumors. Children with this treatment-recalcitrant form of obesity have excess rates of metabolic sequelae compared to otherwise healthy children with similar obesity, and later experience excess mortality related to cardiometabolic disease. In this pilot trial, our objective is to gather key preliminary data about phentermine/topiramate (Ph/T) that is FDA-approved for common obesity but has never been tested in HO. The subset of individuals with HO who experience hyperphagia or excess daytime sleepiness may benefit from the Ph/T-induced decrease in appetite and increase in alertness. Preliminary assessments of safety, adverse events, dosing (Aim 1), as well as of efficacy (% BMI loss, Aim 2) will be made in a 28-week parallel-arm double-blinded Phase 2 placebo-controlled clinical trial in 6-28-year-old individuals with HO.
• Males and Females; Ages 6-28 years (inclusive)
• History of rapid weight gain related to tumor onset or treatment, as assessed by an experienced endocrinologist (for example, change in BMI z-score \> 0.2 and/or BMI +5% during the first 6 months following tumor treatment)
• Obesity (BMI \> 95th%ile for age/sex using CDC 2000 reference for under 18; BMI \> 30 kg/m2 for 18+ years)
• Recent evidence of hypothalamic injury by brain MRI with central review; \>6 months status-post definitive therapy (surgery, chemotherapy, or radiation); no major operations/surgeries planned during the study period.
• Stable on pituitary replacement\* and/or appetite-modulating medications (including stimulants) for at least 2 months. \*Adjustments of less than 25% (\<25%) are permitted to hydrocortisone, growth hormone or thyroid hormone. Sex steroids and DDAVP are exempt.
• Post-menarchal females must use a highly effective form of contraception, unless hypogonadotropic hypogonadism is documented. All participating females of child-bearing potential will have pregnancy testing as outlined in the protocol.
• Participants must be able to communicate well with the investigative team, must comply with requirements of the study, and be able to provide written informed consent and/or assent for individuals less than 18y with consent of a parent/legal guardian.