{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T07:06:15Z","timestamp":1784099175186,"version":"3.55.0"},"reference-count":19,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Behav. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Acquired hypothalamic obesity (HO), caused by hypothalamic injury, is characterized by hyperphagia (i.e., insatiable hunger and abnormal food-seeking behaviors), reduced energy expenditure, and accelerated and sustained weight gain, all of which substantially impact quality of life. In the Phase 3, randomized, double-blind, placebo-controlled TRANSCEND trial (\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      identifier: NCT05774756), setmelanotide demonstrated significant improvements compared with placebo in body mass index, hunger, symptoms of hyperphagia, and quality of life in participants with acquired HO. This substudy further characterizes changes in hunger, weight, energy level, and physical activity with setmelanotide and assesses the perceived meaningfulness of such benefits to patients and their caregivers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      In-depth, 75-min qualitative interviews were conducted from July 2024 to January 2025 with eligible and consented English-speaking TRANSCEND trial participants or their caregivers in the United States. Interviews followed a semistructured interview guide tailored to facilitate discussion about participant experiences or caregiver observations regarding changes in weight, hunger, and energy level before and during trial participation. Interview participants were also asked to describe the perceived meaningfulness of any changes experienced. Interviews were audio recorded and transcribed; thematic analysis was conducted using ATLAS.ti (\n                      <jats:ext-link>https:\/\/atlasti.com\/<\/jats:ext-link>\n                      ).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of the 30 interview participants, 14 were trial participants (4 adolescents and 10 adults) and 16 were caregivers of participants aged &amp;lt; 12 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 8) and \u2265 12 years (\n                      <jats:italic>n<\/jats:italic>\n                      = 8); 23 received setmelanotide and 7 received placebo. All interview participants reported insatiable hunger and accelerated and sustained weight gain after hypothalamic injury but before starting the trial; 29 of 30 interview participants reported reduced energy level. Consistently, trial participants who received setmelanotide and their caregivers reported beneficial changes in hunger, weight, energy level, and physical activity, and indicated these changes were meaningful, while in placebo-treated participants, no such changes were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings support the Phase 3 TRANSCEND efficacy outcomes pertaining to weight, hunger, energy levels, and quality of life and that the impactful changes with setmelanotide in patients with acquired HO and their caregivers extend beyond body mass index and weight reduction.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      , identifier NCT05774756.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnbeh.2026.1830070","type":"journal-article","created":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T06:09:25Z","timestamp":1784095765000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Quality of life improvements with setmelanotide treatment in acquired hypothalamic obesity: TRANSCEND trial interview results from US participants"],"prefix":"10.3389","volume":"20","author":[{"given":"Christian L.","family":"Roth","sequence":"first","affiliation":[{"name":"Seattle Children\u2019s Research Institute","place":["Seattle, WA, United States"]},{"name":"Department of Pediatrics, Seattle Children\u2019s Hospital, University of Washington","place":["Seattle, WA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan A.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Rady Children\u2019s Hospital, University of California, San Diego","place":["San Diego, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shana E.","family":"McCormack","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Diabetes, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]},{"name":"Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania","place":["Philadelphia, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katie Larson","family":"Ode","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Iowa\u2013Stead Family Children\u2019s Hospital, Fraternal Order of Eagles Diabetes Research Center, University of Iowa","place":["Iowa City, IA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan M.","family":"Kelsey","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Colorado School of Medicine and Children\u2019s Hospital Colorado","place":["Aurora, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jieruo","family":"Liu","sequence":"additional","affiliation":[{"name":"Rhythm Pharmaceuticals, Inc.","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claire","family":"Ervin","sequence":"additional","affiliation":[{"name":"RTI Health Solutions","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Usha G.","family":"Mallya","sequence":"additional","affiliation":[{"name":"Rhythm Pharmaceuticals, Inc.","place":["Boston, MA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lindsey","family":"Norcross","sequence":"additional","affiliation":[{"name":"RTI Health Solutions","place":["Durham, NC, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer L.","family":"Miller","sequence":"additional","affiliation":[{"name":"Pediatric Endocrinology, Department of Pediatrics, College of Medicine, University of Florida","place":["Gainesville, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"862817","DOI":"10.3389\/fendo.2022.862817","article-title":"Resting energy expenditure and body composition in children and adolescents with genetic, hypothalamic, medication-induced or multifactorial severe obesity.","volume":"13","author":"Abawi","year":"2022","journal-title":"Front. 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