Studies a GLP-1 medicine and hormone rhythms in teen girls with PCOS and obesity

AI summary

From the trial's eligibility criteria. Machine-read from the registry text on this page, so it can be wrong. The registry text below and the trial team decide who can take part.

The trial is looking for girls aged 12 to 18 with obesity and polycystic ovary syndrome (PCOS) who still have symptoms after at least 4 months of lifestyle changes.

Age

12 to 18 years, and at least 2 years after the first period.

Sex

Female only.

Disease stage

PCOS by NIH criteria: infrequent periods (cycles under 21 or over 35 days) and high androgen (male-type hormone) levels. Obesity at or above the 95th percentile. Good overall health.

Earlier treatment

Symptoms must persist despite lifestyle changes for at least 4 months. Cannot have had GLP-1 agonists, birth control pills or progesterone for at least 6 weeks before screening.

Biomarker or test result

Testosterone level or free androgen index above the reference range for the Tanner stage.

Main reasons for not taking part

• Diabetes mellitus
• Abnormal thyroid function tests at screening
• Non-classic congenital adrenal hyperplasia or high prolactin
• Personal or family history of medullary thyroid carcinoma or MEN2, or history of pancreatitis
• Currently pregnant or ever pregnant

The registry criteria, word for word

Check if you might fit

Answer for yourself. This is not a decision: only the study team can say whether you can take part.

• Are you between 12 and 18 years old?YesNo

What the trial wants to find out

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.

The group in the trial

• Females ages 12 to 18 years, at least 2 years post-menarche, with obesity and PCOS..

  Females ages 12 to 18 years, at least 2 years post-menarche, with obesity (BMI equal to or more than the 95th percentile for age) and with PCOS, by NIH criteria: oligomenorrhea (menstrual cycles \<21 or \>35 days) \[4\] and hyperandrogenism (testosterone level or free androgen index (FAI) \> refence range for tanner stage) and in good overall health. FAI is calculated as total testosterone\*100/sex hormone binding globulin.

  Treatment: GLP-1 Receptor Agonists