Treating PCOS With Semaglutide vs Active Lifestyle Intervention

NAFLD Clinical Trial

— TEAL  

Official title:

Treating PCOS With Semaglutide vs Active Lifestyle Intervention

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03919929
• Other study ID #: 19-0636
• Secondary ID: 1R01DK120612-01A
• Status: Active, not recruiting
• Phase: Phase 2/Phase 3
• Start date: May 3, 2019
• Est. completion date: July 2024

Study information

• Verified date: January 2024
• Source: University of Colorado, Denver
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Girls with obesity and polycystic ovarian syndrome will receive either glucagon like peptide-1 receptor agonist therapy or a dietary intervention for 12 weeks to decrease the metabolic syndrome, in particular to lower hepatic fat and improve insulin sensitivity.

Description:

In obese girls with polycystic ovarian syndrome, testosterone and obesity combine to create unique pathology to increase metabolic disease including fatty liver and insulin resistance, which may be mediated by altered glucagon like peptide-1 activity. The investigators will treat girls with obesity and polycystic ovarian syndrome for 4 months with a glucagon like peptide-1 receptor agonist compared to dietary intervention to primarily lower hepatic fat and secondarily improve whole body and adipose insulin sensitivity. Mechanisms of hepatic metabolism, including rates of de novo lipogenesis and relative mitochondrial flux will also be assessed.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 60
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 12 Years to 21 Years

Eligibility

Inclusion Criteria:

1. Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.

2. BMI equal or greater than the 90th percentile for age and gender

3. PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >12 months post-menarche and clinical or biochemical hypertestosteronemia

4. Participants cannot be on hormonal contraception, so participants should remain abstinent or use reliable non-hormonal contraception (e.g. copper IUD) for the entire study period. For participants who receive semaglutide, they should avoid pregnancy for at least 2 months after stopping medication to avoid fetal exposure to the medication.

Exclusion Criteria:

1. Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2). Family history of medullary thyroid cancer or thyroid nodule palpated by endocrinologist at screening.

2. Use of medications known to affect insulin sensitivity: metformin (cannot have been used in the 3 months prior to screening), oral glucocorticoids within 10 days, atypical antipsychotics, immunosuppressant agents, HIV medications, hormonal contraception (cannot have been used in the 6 months prior to screening). Dermal patch or vaginal ring contraception methods.Weight loss medications or stimulants. Use of other products containing other GLP-1 agonists.

3. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.

4. Severe illness requiring hospitalization within 60 days.

5. Diabetes, defined as Hemoglobin A1C > 6.4%

6. BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs. or <84 lbs.

7. Anemia, defined as Hemoglobin < 11 mg/dL

8. Diagnosed major psychiatric or developmental disorder limiting informed consent.

9. Implanted metal devices that are not compatible with MRI

10. Use of blood pressure medications.

11. Known liver disease other than NAFLD or AST or ALT >100 IU/L.

12. Personal history of pancreatitis

13. Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2

14. History of severe GI disease (e.g. gastroparesis)

15. History of gallstones

16. Untreated thyroid disease

17. History of hypersensitivity to semaglutide

18. Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).

19. Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder

Related Conditions & MeSH terms

• Adolescent Obesity
• NAFLD
• PCOS
• Pediatric Obesity

Intervention

Drug:
• Semaglutide 3mg and 7mg [Rybelsus]
Once daily oral tablet of semaglutide for 4 months

Other:
• Weight loss diet
Prescribed weight loss diet to match weight loss in Drug arm

Locations

Country	Name	City	State
United States	University of Colorado Anshutz Medical Campus/Children's Hospital Colorado	Aurora	Colorado

Sponsors (2)

Lead Sponsor	Collaborator
University of Colorado, Denver	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Evaluation of Mitochondrial function via change in ratios of direct to indirect hepatic carbon flux in newly synthesized triglycerides	OSTT with UC13 glycerol baseline and 12 weeks	Baseline and 12 weeks
Other	Change in Free Androgen Index	The Free Androgen Index (FAI) is a test for hyperandrogenism in women, using testosterone and sex hormone binding globulin (SHBG) as markers. Typical values for the FAI in women are 7-10, and FAI is usually elevated in women with PCOS. The change in FAI will be calculated after 12 weeks of diet or semaglutide intervention.	Baseline and 12 weeks
Primary	Change in Hepatic Fat Fraction	Change from baseline in presence/severity of hepatic fat fraction will be measured with MRI, and calculated via the Dixon method as the proton density hepatic fat fraction, which ranges from 0-75%.	Baseline and 12 weeks
Primary	Change in Weight	Change in weight will be calculated for each group (diet and semaglutide), and both the absolute and relative weight changes between the two groups will be reported.	Baseline and 12 weeks
Secondary	Change in Rate of De Novo Lipogenesis	Change from baseline of the rate of overnight de novo lipogenesis will be measured utilizing stable isotope methods with deuterated water, and expressed as the rate of newly synthesized lipids in the serum triglyceride fraction.	Baseline and 12 weeks
Secondary	Change in Whole Body Insulin Sensitivity	Participants will undergo a 75 gram oral glucose tolerance test, and the change from baseline in whole body insulin sensitivity will be expressed as Si, calculated via the oral minimal model.	Baseline and 12 weeks
Secondary	Change in Adipose Insulin Sensitivity	Change from baseline of adipose insulin sensitivity will be calculated as the percent suppression of free fatty acids, and the nadir of free fatty acids during the oral glucose tolerance test.	Baseline and 12 weeks