Clinical trial

Effects of Glucagon-like Peptide-1 (GLP-1) Agonist in Neuro-reproductive Function in Obese Adolescent Females With Polycystic Ovary Syndrome (PCOS)

Recruiting now · Not applicable · 1 countries · Registry ID NCT07169136

Recruiting nowNot applicableObservational

What this study is about

The prevalence of childhood obesity in the United States has more than tripled in the past four decades affecting one in every five adolescent girls and is disproportionally higher among racial and/or ethnic minorities. Normal puberty onset and progression is dependent on normal hypothalamic-pituitary-gonadal (HPG) axis which is affected by whole body metabolism. Gonadotropin-releasing hormone (GnRH) and gonadotropins, LH and FSH, are released in a pulsatile manner for appropriate sex steroids production and gonadal function. Proper pulsatility in the GnRH system is disrupted by a significant change in energy balance such as in obesity. Polycystic Ovary Syndrome (PCOS) is the most common neuroendocrine dysfunction in women of reproductive age. Glucagon-like peptide-1 (GL-1), a peptide hormone secreted by the intestinal enteroendocrine L-cells following glucose and fat intake, stimulates insulin release by the pancreas in response to glucose, decreases gastric emptying and inhibits glucagon secretion. GLP-1 receptors are present in the hypothalamic nuclei and pituitary gland; and it is thought that GLP-1 may directly stimulate GnRH secretion and partially regulate reproduction. In animal studies, GLP-1 was found to stimulate GnRH secretion, to regulate kisspeptin (Kiss-1) mRNA and GnRH mRAN expression. GLP-1 receptor agonists are FDA-approved to treat adults and adolescents with obesity. Although the impact of GLP-1 receptor agonists in reproductive health has been investigated in preclinical trials, and in men with obesity and functional hypogonadism, no studies to date have investigated the impact of GLP-1 receptor agonists in female neuroendocrine function, particularly in youth. The goal of this proposal is to gather critical preliminary data to investigate, in a group of obese adolescent females with PCOS, the impact of GLP-1 agonist administration in addition to lifestyle modifications on the neuroendocrine rhythms - LH frequency and amplitude (principal); body composition, adiposity; and carbohydrate metabolism and insulin sensitivity. To accomplish these aims, we will recruit a cohort of up to 20 adolescents ages 12-18 years, at least 2 years post-menarche, with obesity, PCOS, by NIH criteria, without carbohydrate intolerance and in otherwise good health. Research volunteers will be advised on lifestyle modifications of diet and exercise as per routine, and a GLP-1 agonist will be started according to the product's label as per FDA guidelines in children with obesity. Medication will be titrated to maximal therapeutic dose, as per routine clinical practice. Participants will be treated for a total of 16 weeks. Neuroendocrine rhythms pre- and post-treatment will be compared.

A promising-looking record is not the same as confirmed eligibility. The study team must review the full criteria and current recruitment status.

Basic eligibility

Age12 Years to 18 Years

SexFemale

Healthy volunteersNot accepted

ConditionPolycystic Ovarian Syndrome in Adolescent Females, Obesity (Disorder)

Full registry criteria

Inclusion Criteria: * Diagnosed with PCOS, by NIH criteria: oligomenorrhea (menstrual cycles \<21 or \>35 days) and hyperandrogenism (testosterone level or free androgen index (FAI) \> refence range for tanner stage) and in good overall health * Obesity (equal to or more than the 95th percentile) * Females ages 12 to 18 years, at least 2 years post-menarche * Participants has persistent symptoms of PCOS and obesity despite lifestyle modifications for at least 4 months. Exclusion Criteria: * Has abnormal thyroid function tests at Screening. * Has suspected or known Diabetes mellitus, impaired fasting glucose, or elevated hemoglobin A1c. * Has non-classic congenital adrenal hyperplasia. * Has hyperprolactinemia. * Has a known history or family history of medullary thyroid carcinoma or MEN2 and history of pancreatitis * Participants receiving prior treatment with metformin, GLP-1 agonists, oral contraception pills, progesterone, or other insulin sensitizers for at least 6 weeks prior to Screening. * Is currently pregnant or has been pregnant.

Treatments and study arms

GLP-1 Receptor Agonists

Drug

Weekly subcutaneous Semaglutide.

Primary outcomes

Change in LH pulse frequency after 4 months of GLP-1 agonist use.Blood sampling will occur at study enrollment and then 4 months post intervention.

LH will be obtained every 20 minutes overnight. LH will be measured using a chemiluminescence assay. Pulse frequency will be calculated using mathematical deconvolution analysis.

Change in average levels of LH and FSH after 4 months of GLP-1 agonist use.Blood sampling will occur at study enrollment and then 4 months post intervention.

LH and FSH will be measured using a chemiluminescence assay.

Change in average levels of Total testosterone and Estradiol after 4 months of GLP-1 agonist use.Blood sampling will occur at study enrollment and then 4 months post intervention.

Total testosterone and estradiol will be measured by liquid chromatography-mass spectrometry

Change in average levels of progesterone after 4 months of GLP-1 agonist use.Blood sampling will occur at study enrollment and then 4 months post intervention.

Progesterone will be measured using immunoassay.

Change in LH amplitude.Blood sampling will occur at study enrollment and then 4 months post intervention.

LH will be obtained every 20 minutes overnight. LH will be measured using a chemiluminescence assay. Pulse amplitude will be calculated using mathematical deconvolution analysis.

Study locations

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Nemours Children's Clinic🇺🇸 Jacksonville, Florida, United States

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Camila Pereira-Eshraghi, MD. MS.Contact

Email · Call 1 + 904-408-7895