Oxytocin for Adolescent Obesity
Recruiting in Palo Alto (17 mi)
Age: < 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Recruiting
Sponsor: Massachusetts General Hospital
Must not be taking: Weight loss drugs
Disqualifiers: Substance abuse, Cardiovascular disease, Epilepsy, others
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This is a randomized, double blind, placebo-controlled study of the effects of intranasal oxytocin in youths with obesity, ages 12-18 years old. Subjects will be randomized to receive intranasal oxytocin or placebo (3 sprays per nostril, 4 times per day) for 12 weeks. Study visits include screening to determine eligibility, 2-part main study visits at baseline, week 8, and week 12, and safety check-in visits at weeks 1, and 4; phone calls at weeks 2, 6, and 10, with a safety follow-up visit 6 weeks after the last dose of study drug. Study procedures include appetite, behavioral, metabolic, and endocrine assessments.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications. However, if you are taking medications or supplements for weight loss, you cannot participate unless you have been on a stable dose with stable weight for at least 3 months.
What evidence supports the effectiveness of the drug oxytocin nasal spray for treating adolescent obesity?
Research shows that oxytocin can help reduce food intake and promote weight loss in both animal models and humans with obesity. Studies have found that oxytocin nasal spray can lead to weight loss by decreasing calorie consumption and increasing energy use, making it a promising option for obesity treatment.12345
Is oxytocin nasal spray safe for use in humans?
How is the drug oxytocin nasal spray different from other obesity treatments?
Oxytocin nasal spray is unique because it targets the brain to help control appetite and energy balance, potentially leading to weight loss without the psychiatric or cardiovascular side effects often seen with other obesity treatments. It works by reducing food intake and increasing energy expenditure, and it can be effective even in cases where the body is resistant to leptin, a hormone that regulates hunger.123410
Eligibility Criteria
This trial is for overweight adolescents aged 12-18 with a BMI in the top 5% for their age and gender. They must be willing to keep their diet and lifestyle unchanged during the study. Those with certain medical conditions, significant recent weight changes, or on specific diets or medications that affect metabolism are excluded.Inclusion Criteria
You agree to keep your current diet and lifestyle throughout the study.
I am between 12 and 18 years old.
My BMI is in the top 5% for my age and gender.
Exclusion Criteria
You currently have an eating disorder that is not under control.
You are following a specialized diet such as gluten-free, vegan, Paleo, Atkins, raw diet, macrobiotic diet.
I have a thyroid condition that hasn't been treated.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
1 visit (in-person)
Treatment
Participants receive intranasal oxytocin or placebo for 12 weeks
12 weeks
Main study visits at baseline, week 8, and week 12; safety check-in visits at weeks 1 and 4; phone calls at weeks 2, 6, and 10
Follow-up
Participants are monitored for safety and effectiveness after treatment
6 weeks
1 safety follow-up visit (in-person)
Treatment Details
Interventions
- Oxytocin nasal spray (Hormone Therapy)
- Placebo (Other)
Trial OverviewThe study tests if oxytocin nasal spray helps with weight loss compared to a placebo. Participants will use either the real spray or placebo four times daily for three months, while researchers monitor appetite, behavior, metabolism, and hormones.
Participant Groups
2Treatment groups
Experimental Treatment
Placebo Group
Group I: OxytocinExperimental Treatment1 Intervention
Oxytocin nasal spray (24 IU nasal spray, 4 times per day for 12 weeks)
Group II: PlaceboPlacebo Group1 Intervention
Placebo nasal spray (24 IU nasal spray, 4 times per day for 12 weeks)
Oxytocin nasal spray is already approved in United States, European Union for the following indications:
🇺🇸 Approved in United States as Pitocin for:
- Induction of labor
- Stimulation of uterine contractions
🇪🇺 Approved in European Union as Syntocinon for:
- Induction of labor
- Stimulation of uterine contractions
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Massachusetts General HospitalBoston, MA
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Who Is Running the Clinical Trial?
Massachusetts General HospitalLead Sponsor
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
National Institutes of Health (NIH)Collaborator
References
Translational and therapeutic potential of oxytocin as an anti-obesity strategy: Insights from rodents, nonhuman primates and humans. [2022]The fact that more than 78 million adults in the US are considered overweight or obese highlights the need to develop new, effective strategies to treat obesity and its associated complications, including type 2 diabetes, kidney disease and cardiovascular disease. While the neurohypophyseal peptide oxytocin (OT) is well recognized for its peripheral effects to stimulate uterine contraction during parturition and milk ejection during lactation, release of OT within the brain is implicated in prosocial behaviors and in the regulation of energy balance. Previous findings indicate that chronic administration of OT decreases food intake and weight gain or elicits weight loss in diet-induced obese (DIO) mice and rats. Furthermore, chronic systemic treatment with OT largely reproduces the effects of central administration to reduce weight gain in DIO and genetically obese rodents at doses that do not appear to result in tolerance. These findings have now been recently extended to more translational models of obesity showing that chronic subcutaneous or intranasal OT treatment is sufficient to elicit body weight loss in DIO nonhuman primates and pre-diabetic obese humans. This review assesses the potential use of OT as a therapeutic strategy for treatment of obesity in rodents, nonhuman primates, and humans, and identifies potential mechanisms that mediate this effect.
A randomized, double-blind, placebo-controlled clinical trial of 8-week intranasal oxytocin administration in adults with obesity: Rationale, study design, and methods. [2023]Obesity affects more than one-third of adults in the U.S., and effective treatment options are urgently needed. Oxytocin administration induces weight loss in animal models of obesity via effects on caloric intake, energy expenditure, and fat metabolism. We study intranasal oxytocin, an investigational drug shown to reduce caloric intake in humans, as a potential novel treatment for obesity.
Oxytocin as an Anti-obesity Treatment. [2022]Obesity is a growing health concern, as it increases risk for heart disease, hypertension, type 2 diabetes, cancer, COVID-19 related hospitalizations and mortality. However, current weight loss therapies are often associated with psychiatric or cardiovascular side effects or poor tolerability that limit their long-term use. The hypothalamic neuropeptide, oxytocin (OT), mediates a wide range of physiologic actions, which include reproductive behavior, formation of prosocial behaviors and control of body weight. We and others have shown that OT circumvents leptin resistance and elicits weight loss in diet-induced obese rodents and non-human primates by reducing both food intake and increasing energy expenditure (EE). Chronic intranasal OT also elicits promising effects on weight loss in obese humans. This review evaluates the potential use of OT as a therapeutic strategy to treat obesity in rodents, non-human primates, and humans, and identifies potential mechanisms that mediate this effect.
The role of oxytocin in regulation of appetitive behaviour, body weight and glucose homeostasis. [2022]Obesity and its associated complications have reached epidemic proportions in the USA and also worldwide, highlighting the need for new and more effective treatments. Although the neuropeptide oxytocin (OXT) is well recognised for its peripheral effects on reproductive behaviour, the release of OXT from somatodendrites and axonal terminals within the central nervous system (CNS) is also implicated in the control of energy balance. In this review, we summarise historical data highlighting the effects of exogenous OXT as a short-term regulator of food intake in a context-specific manner and the receptor populations that may mediate these effects. We also describe what is known about the physiological role of endogenous OXT in the control of energy balance and whether serum and brain levels of OXT relate to obesity on a consistent basis across animal models and humans with obesity. We describe recent data on the effectiveness of chronic CNS administration of OXT to decrease food intake and weight gain or to elicit weight loss in diet-induced obese (DIO) and genetically obese mice and rats. Of clinical importance is the finding that chronic central and peripheral OXT treatments both evoke weight loss in obese animal models with impaired leptin signalling at doses that are not associated with visceral illness, tachyphylaxis or adverse cardiovascular effects. Moreover, these results have been largely recapitulated following chronic s.c. or intranasal treatment in DIO non-human primates (rhesus monkeys) and obese humans, respectively. We also identify plausible mechanisms that contribute to the effects of OXT on body weight and glucose homeostasis in rodents, non-human primates and humans. We conclude by describing the ongoing challenges that remain before OXT-based therapeutics can be used as a long-term strategy to treat obesity in humans.
Metabolic Effects of Oxytocin. [2022]There is growing evidence that oxytocin (OXT), a hypothalamic hormone well recognized for its effects in inducing parturition and lactation, has important metabolic effects in both sexes. The purpose of this review is to summarize the physiologic effects of OXT on metabolism and to explore its therapeutic potential for metabolic disorders. In model systems, OXT promotes weight loss by decreasing energy intake. Pair-feeding studies suggest that OXT-induced weight loss may also be partly due to increased energy expenditure and/or lipolysis. In humans, OXT appears to modulate both homeostatic and reward-driven food intake, although the observed response depends on nutrient milieu (eg, obese vs. nonobese), clinical characteristics (eg, sex), and experimental paradigm. In animal models, OXT is anabolic to muscle and bone, which is consistent with OXT-induced weight loss occurring primarily via fat loss. In some human observational studies, circulating OXT concentrations are also positively associated with lean mass and bone mineral density. The impact of exogenous OXT on human obesity is the focus of ongoing investigation. Future randomized, placebo-controlled clinical trials in humans should include rigorous, standardized, and detailed assessments of adherence, adverse effects, pharmacokinetics/pharmacodynamics, and efficacy in the diverse populations that may benefit from OXT, in particular those in whom hypothalamic OXT signaling may be abnormal or impaired (eg, individuals with Sim1 deficiency, Prader-Willi syndrome, or craniopharyngioma). Future studies will also have the opportunity to investigate the characteristics of new OXT mimetic peptides and the obligation to consider long-term effects, especially when OXT is given to children and adolescents. (Endocrine Reviews XX: XX - XX, 2020).
A Review of the Safety, Efficacy and Mechanisms of Delivery of Nasal Oxytocin in Children: Therapeutic Potential for Autism and Prader-Willi Syndrome, and Recommendations for Future Research. [2018]In this article, we conduct a comprehensive review of existing evidence for the safety and therapeutic potential of intranasal oxytocin in pediatric populations. Unique considerations for dosing and delivery of oxytocin to the nasal passageway in pediatric populations and methods to promote adherence are reviewed. Intranasal oxytocin has been administered to 261 children in three open-label studies and eight randomized controlled trials. To date, the only published results in pediatric populations have focused on autism spectrum disorder (ASD) and Prader-Willi syndrome (PWS). Results regarding efficacy for improving social impairment in ASD are equivocal, partially due to mixed methodological designs, dosing regimens, and outcome measures. At present, there is no randomized controlled evidence that oxytocin provides benefit to individuals with PWS. There is no clear evidence of a link between oxytocin administration and any specific adverse event. Adverse events have been assessed using medical interviews, open reports, checklists, and physiological assessments. Adverse events reports have been largely classified as mild (n = 93), with few moderate (n = 9) or severe (n = 3) events reported. There were 35 additional adverse events reported, without severity ratings. Severe events, hyperactivity and irritability, occurred at first administration in both placebo and oxytocin groups, and subsided subsequent to discontinuation. We note that adverse event monitoring is inconsistent and often lacking, and reporting of its relationship to the study drug is poor. Only one study reported adherence data to suggest high adherence. Recommendations are then provided for the delivery of nasal sprays to the nasal passageway, monitoring, and reporting of efficacy, safety, and adherence for oxytocin nasal spray trials in pediatric populations.
No side-effects of single intranasal oxytocin administration in middle childhood. [2019]Despite growing interest in the (therapeutic) use of intranasal oxytocin administration in children, the potential side-effects of intranasal oxytocin have remained largely unclear to date. The current study is the first double-blind randomized controlled trial to examine side-effects following single administration of oxytocin nasal spray in elementary school-aged children.
Synthetic oxytocin. [2018]A synthetic oxytocin, Syntocinon(R), was used in 3,342 obstetrical patients for a wide variety of indications. It was concluded that the preparation is as effective as natural oxytocin.(1) There were no side effects observed, particularly vasospasm or anaphylactic reaction. Its use in clinical obstetrics can be recommended provided there is a proper indication for its use and the need for close supervision and individual adjustment of dosage is recognized.
Systematic review and meta-analysis of reported adverse events of long-term intranasal oxytocin treatment for autism spectrum disorder. [2018]Recent studies have suggested oxytocin as a possible drug to treat social deficits caused by autism spectrum disorder (ASD), but the safety of intranasal oxytocin in autistic patients has not been established. The aim of this review was to characterize the side-effect profile of long-term intranasal oxytocin in treatment of ASD compared to placebo. All randomized controlled trials of intranasal oxytocin in the treatment of ASD published before 1 January 2017 that reported safety data were identified from databases, including PubMed, Embase, Cochrane Library, and International Pharmaceutical Abstract. Relevant data from the selected studies were then extracted for meta-analysis to estimate the pooled risk ratio for the most common adverse events. Descriptive analysis of severe adverse events was also conducted. Of the 223 participants in the five included studies, 123 were given oxytocin and 100 were given placebos. Nasal discomfort (14.3%), tiredness (7.2%), irritability (9.0%), diarrhea (4.5%), and skin irritation (4.5%) were the most common adverse events. None of these common adverse events was statistically associated with treatment allocation according to meta-analysis using pooled data (all P-values > 0.1). Five severe adverse events were reported, namely aggression (one in placebo, two in oxytocin) and seizures (one in placebo, one in oxytocin). Results from this systematic review support intranasal oxytocin as well tolerated and safe for use in the ASD population. Larger clinical trials should be conducted to establish the efficacy of intranasal oxytocin as a treatment of ASD.
Chronic Oxytocin Administration as a Treatment Against Impaired Leptin Signaling or Leptin Resistance in Obesity. [2018]This review summarizes the existing literature on the effects of oxytocin administration in the treatment of obesity in different animal models and in humans, focusing on the central control of food intake, the oxytocin effects on adipose tissue, and the relationships between oxytocin and leptin. Oxytocin is a hypothalamic nonapeptide synthesized mainly in the paraventricular and supraoptic nuclei projecting to the pituitary, where it reaches the peripheral circulation, as well as to other brain regions. Moreover, leptin modulates oxytocin levels and activates oxytocin neurons in the hypothalamic paraventricular nucleus, which innervates the nucleus of the solitary tract, partly responsible for the brain-elicited oxytocin effects. Taking into account that oxytocin is located downstream leptin, it was hypothesized that oxytocin treatment would be effective in decreasing body weight in leptin-resistant DIO animals, as well as in those with leptin or with leptin receptor deficiency. Several groups have demonstrated that in such animal models (rats, mice, and rhesus monkeys), central or peripheral oxytocin administration decreases body weight, mainly due to a decrease in fat mass, demonstrating that an oxytocin treatment is able to partly overcome leptin deficiency or resistance. Moreover, a pilot clinical study demonstrated the efficiency of oxytocin in the treatment of obesity in human subjects, confirming the results obtained in the different animal models. Larger multicenter studies are now needed to determine whether the beneficial effects of oxytocin treatment can apply not only to obese but also to type 2 diabetic patients. These studies should also shed some light on the molecular mechanisms of oxytocin action in humans.