학술논문
A Pilot Randomized Clinical Trial of Intranasal Oxytocin to Promote Weight Loss in Individuals With Hypothalamic Obesity
Clinical Research Article
Clinical Research Article
Document Type
Academic Journal
Author
McCormack, Shana E.; Wang, Zi; Wade, Kristin L.; Dedio, Anna; Cilenti, Nicolette; Crowley, Julia; Plessow, Franziska; Bamba, Vaneeta; Roizen, Jeffrey D.; Jiang, Yaoguang; Stylli, Jack; Ramakrishnan, Arjun; Platt, Michael L.; Shekdar, Karuna; Fisher, Michael J.; Vetter, Victoria L.; Hocking, Matthew; Xiao, Rui; Lawson, Elizabeth A.
Source
Journal of the Endocrine Society. May 2023, Vol. 7 Issue 5
Subject
Language
English
ISSN
2472-1972
Abstract
Hypothalamic obesity is a rare form of treatment-resistant obesity that frequently develops in individuals with brain tumors affecting the hypothalamus and pituitary, such as craniopharyngioma [1, 2]. Craniopharyngioma is a [...]
Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6 kg (95% CI: - 2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was welltolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits. Key Words: oxytocin, neuroendocrinology, hypopituitarism, pediatric endocrinology, hypothalamic obesity, craniopharyngioma Abbreviations: BMDCS, Bone Mineral Density Cohort Study Physical Activity; BMI, body mass index; CHOP, Children's Hospital of Philadelphia; CTCAE, Common Terminology Criteria for Adverse Events; DDAVP, desmopressin; DI, diabetes insipidus; ECG, electrocardiography; FAD-GFS, Family Assessment Device General Function scale; IQR, interquartile range; MRI, magnetic resonance imaging; Neuro-QOL, Quality of Life in Neurological Disorders; OXT, oxytocin; PWS, Prader-Willi syndrome; SMURF, Safety Monitoring Uniform Report Form; SSRT, stop-signal reaction time.
Context: Hypothalamic obesity is a rare, treatment-resistant form of obesity. In preliminary studies, the hypothalamic hormone oxytocin (OXT) has shown promise as a potential weight loss therapy. Objective: To determine whether 8 weeks of intranasal OXT (vs 8 weeks of placebo) promotes weight loss in children, adolescents, and young adults with hypothalamic obesity. Methods: This randomized, double-blind, placebo-controlled, crossover pilot trial (NCT02849743), conducted at an outpatient academic medical center, included patients aged 10 to 35 years with hypothalamic obesity from hypothalamic/pituitary tumors. Participants received intranasal OXT (Syntocinon, 40 USP units/mL, 4 IU/spray) vs excipient-matched placebo, 16 to 24 IU 3 times daily at mealtimes. Weight loss attributable to OXT vs placebo and safety (adverse events) were assessed. Results: Of 13 individuals randomized (54% female, 31% pre-pubertal, median age 15.3 years, IQR 13.3-20.6), 10 completed the entire study. We observed a nonsignificant within-subject weight change of -0.6 kg (95% CI: - 2.7, 1.5) attributable to OXT vs placebo. A subset (2/18 screened, 5/13 randomized) had prolonged QTc interval on electrocardiography prior to screening and/or in both treatment conditions. Overall, OXT was well-tolerated, and adverse events (epistaxis and nasal irritation, headache, nausea/vomiting, and changes in heart rate, blood pressure, and QTc interval) were similar between OXT and placebo. In exploratory analyses, benefits of OXT for anxiety and impulsivity were observed. Conclusion: In this pilot study in hypothalamic obesity, we did not detect a significant impact of intranasal OXT on body weight. OXT was welltolerated, so future larger studies could examine different dosing, combination therapies, and potential psychosocial benefits. Key Words: oxytocin, neuroendocrinology, hypopituitarism, pediatric endocrinology, hypothalamic obesity, craniopharyngioma Abbreviations: BMDCS, Bone Mineral Density Cohort Study Physical Activity; BMI, body mass index; CHOP, Children's Hospital of Philadelphia; CTCAE, Common Terminology Criteria for Adverse Events; DDAVP, desmopressin; DI, diabetes insipidus; ECG, electrocardiography; FAD-GFS, Family Assessment Device General Function scale; IQR, interquartile range; MRI, magnetic resonance imaging; Neuro-QOL, Quality of Life in Neurological Disorders; OXT, oxytocin; PWS, Prader-Willi syndrome; SMURF, Safety Monitoring Uniform Report Form; SSRT, stop-signal reaction time.