BACKGROUND: Acquired hypothalamic obesity (aHO), caused by hypothalamic injury, can lead to insatiable hunger along with abnormal food-seeking behaviors (hyperphagia), accelerated weight gain, and reduced health-related quality of life. There are no approved aHO treatments, and understanding patients’ lived experiences is crucial to supporting the evaluation of potential treatments. Setmelanotide is being investigated as a treatment for aHO in an ongoing Phase 3, randomized, placebo-controlled trial (TRANSCEND; NCT05774756). To contextualize trial results and characterize pre-trial aHO burden, TRANSCEND participants or their caregivers were interviewed in this sub-study.
METHODS: Qualitative, remote interviews were conducted from July 2024 to January 2025 with English-speaking trial participants (aged ≥12 years) or their primary caregivers (for those aged <12 years or ≥12 years who were unable to self-report) living in the United States. Semi-structured interview guides were tailored to facilitate discussion about participants’ experiences or caregivers’ observations (e.g., changes in weight, hunger, energy levels) after hypothalamic injury. Interviews were audio recorded and transcribed for thematic analysis using ATLAS.ti.
RESULTS: Thirty individuals (24 female) were interviewed: 14 trial participants (4 adolescent, 10 adult) and 16 caregivers. Trial participants’ mean (SD) age at the time of hypothalamic injury was 8.3 (5.7) years. All 30 of those interviewed reported increased hunger and accelerated weight gain post injury, with 29 of 30 indicating never (n=15) or rarely (n=14) feeling full. This intense hunger and lack of or reduced satiety post injury reportedly led to increased consumption and an extreme lack of control over eating for 28 of the 30 interviewed individuals. Those interviewed described a continual struggle between the trial participant seeking food and the caregiver monitoring/limiting food. This fixation with food, plus decrements in energy levels (n=29/30) and physical activity (n=28/30) post injury, contributed to weight gain as well as mental, social, and familial impacts. In attempts to mitigate hunger and weight gain, 18 of the 30 interviewed individuals reported prescription medication use prior to the TRANSCEND trial—most commonly stimulants (n=9) and glucagon-like peptide-1 receptor agonists (n=7)—with only 5 individuals reporting weight loss, which was described as limited or temporary.
CONCLUSIONS: Experiences and observations with aHO before the TRANSCEND trial and post hypothalamic injury were characterized by substantial hunger, accelerated weight gain, fatigue, and reductions in physical activity/function, which had severe impacts on trial participants’ and caregivers’ overall quality of life. This study’s findings support the assessment of these concepts in the evaluation of treatment benefit in aHO studies.
Skip to main content
