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Treating PCOS With Semaglutide vs Active Lifestyle Intervention (TEAL)

Primary Purpose

PCOS, Adolescent Obesity, NAFLD

Status

Recruiting

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Semaglutide 3mg and 7mg [Rybelsus]

Weight loss diet

About this trial

This is an interventional treatment trial for PCOS focused on measuring Insulin Resistance

Eligibility Criteria

12 Years - 21 Years (Child, Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week.
BMI equal or greater than the 90th percentile for age and gender
PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >12 months post-menarche and clinical or biochemical hypertestosteronemia
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:

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.
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.
Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study.
Severe illness requiring hospitalization within 60 days.
Diabetes, defined as Hemoglobin A1C > 6.4%
BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs. or <84 lbs.
Anemia, defined as Hemoglobin < 11 mg/dL
Diagnosed major psychiatric or developmental disorder limiting informed consent.
Implanted metal devices that are not compatible with MRI
Use of blood pressure medications.
Known liver disease other than NAFLD or AST or ALT >100 IU/L.
Personal history of pancreatitis
Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2
History of severe GI disease (e.g. gastroparesis)
History of gallstones
Untreated thyroid disease
History of hypersensitivity to semaglutide
Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma).
Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder

Sites / Locations

University of Colorado Anshutz Medical Campus/Children's Hospital ColoradoRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Diet Intervention

GLP-1 Intervention

Arm Description

Weight loss with dietary intervention

Participants will take a daily oral tablet of semaglutide for 4 months.

Outcomes

Primary Outcome Measures

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%.

Secondary Outcome Measures

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.

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.

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.

Full Information

NCT ID

NCT03919929

First Posted

April 15, 2019

Last Updated

June 6, 2023

Sponsor

University of Colorado, Denver

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

1. Study Identification

Unique Protocol Identification Number

NCT03919929

Brief Title

Treating PCOS With Semaglutide vs Active Lifestyle Intervention

Acronym

TEAL

Official Title

Treating PCOS With Semaglutide vs Active Lifestyle Intervention

Study Type

Interventional

2. Study Status

Record Verification Date

June 2023

Overall Recruitment Status

Recruiting

Study Start Date

May 3, 2019 (Actual)

Primary Completion Date

July 2024 (Anticipated)

Study Completion Date

July 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Colorado, Denver

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

Brief 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.

Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

PCOS, Adolescent Obesity, NAFLD

Keywords

Insulin Resistance

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2, Phase 3

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Diet Intervention

Arm Type

Active Comparator

Arm Description

Weight loss with dietary intervention

Arm Title

GLP-1 Intervention

Arm Type

Experimental

Arm Description

Participants will take a daily oral tablet of semaglutide for 4 months.

Intervention Type

Drug

Intervention Name(s)

Semaglutide 3mg and 7mg [Rybelsus]

Other Intervention Name(s)

GLP-1 receptor agonist

Intervention Description

Once daily oral tablet of semaglutide for 4 months

Intervention Type

Other

Intervention Name(s)

Weight loss diet

Intervention Description

Prescribed weight loss diet to match weight loss in Drug arm

Primary Outcome Measure Information:

Title

Change in Hepatic Fat Fraction

Description

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%.

Time Frame

Baseline and 12 weeks

Secondary Outcome Measure Information:

Title

Change in Rate of De Novo Lipogenesis

Description

Time Frame

Baseline and 12 weeks

Title

Change in Whole Body Insulin Sensitivity

Description

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.

Time Frame

Baseline and 12 weeks

Title

Change in Adipose Insulin Sensitivity

Description

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.

Time Frame

Baseline and 12 weeks

Other Pre-specified Outcome Measures:

Title

Evaluation of Mitochondrial function via change in ratios of direct to indirect hepatic carbon flux in newly synthesized triglycerides

Description

OSTT with UC13 glycerol baseline and 12 weeks

Time Frame

Baseline and 12 weeks

10. Eligibility

Sex

Female

Gender Based

Yes

Minimum Age & Unit of Time

12 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Sedentary- less than 2 hours of moderate (jogging, swimming etc) exercise a week. BMI equal or greater than the 90th percentile for age and gender PCOS per the most stringent NIH criteria adapted for adolescents (irregular menses >12 months post-menarche and clinical or biochemical hypertestosteronemia 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: 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. 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. Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study. Severe illness requiring hospitalization within 60 days. Diabetes, defined as Hemoglobin A1C > 6.4% BMI percentile less than the 90th percentile for age and sex. Weight >325 lbs. or <84 lbs. Anemia, defined as Hemoglobin < 11 mg/dL Diagnosed major psychiatric or developmental disorder limiting informed consent. Implanted metal devices that are not compatible with MRI Use of blood pressure medications. Known liver disease other than NAFLD or AST or ALT >100 IU/L. Personal history of pancreatitis Known renal disease of any severity or an eGFR at screening of <45ml/min/1.73m2 History of severe GI disease (e.g. gastroparesis) History of gallstones Untreated thyroid disease History of hypersensitivity to semaglutide Other causes of hyperandrogenism (example: tumor, CAH) or amenorrhea (untreated thyroid disease, tumor, primary ovarian failure, prolactinoma). Active symptoms or undergoing treatment for anorexia nervosa or binging/purging disorder

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Melanie Cree-Green, MD, PhD

Phone

720-777-5743

melanie.green@childrenscolorado.org

First Name & Middle Initial & Last Name or Official Title & Degree

Yesenia Garcia-Reyes, MS

Phone

720-777-6984

yesenia.garciareyes@childrenscolorado.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Melanie Cree-Green, MD, PhD

Organizational Affiliation

Children's Hospital Colorado

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Colorado Anshutz Medical Campus/Children's Hospital Colorado

City

Aurora

State/Province

Colorado

ZIP/Postal Code

80045

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Yesenia Garcia Reyes

Phone

720-777-6984

yesenia.garciareyes@childrenscolorado.org

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Treating PCOS With Semaglutide vs Active Lifestyle Intervention

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