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Treating PCOS With Exenatide vs Active Lifestyle Intervention (TEAL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details. Identifier: NCT03919929
Recruitment Status : Not yet recruiting
First Posted : April 18, 2019
Last Update Posted : September 26, 2019
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
University of Colorado, Denver

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.

Condition or disease Intervention/treatment Phase
PCOS Adolescent Obesity NAFLD Drug: Exenatide 2 MG [Bydureon] Other: Weight loss diet Phase 2 Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Treating PCOS With Exenatide vs Active Lifestyle Intervention
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : July 2024
Estimated Study Completion Date : July 2024

Resource links provided by the National Library of Medicine

Drug Information available for: Exenatide

Arm Intervention/treatment
Active Comparator: Diet Intervention
Weight loss with dietary intervention
Other: Weight loss diet
Prescribed weight loss diet to match weight loss in Drug arm

Experimental: GLP-1 Intervention
Participants will receive long-acting Exenatide once a week for 12 weeks.
Drug: Exenatide 2 MG [Bydureon]
Exenatide once weekly for 12 weeks
Other Name: GLP-1 receptor agonist

Primary Outcome Measures :
  1. Change in Hepatic Fat Fraction [ Time Frame: Baseline and 12 weeks ]
    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 :
  1. Change in Rate of De Novo Lipogenesis [ Time Frame: Baseline and 12 weeks ]
    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.

  2. Change in Whole Body Insulin Sensitivity [ Time Frame: Baseline and 12 weeks ]
    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.

  3. Change in Adipose Insulin Sensitivity [ Time Frame: Baseline and 12 weeks ]
    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.

Other Outcome Measures:
  1. Change in Relative Hepatic Mitochondrial Flux [ Time Frame: Baseline and 12 weeks ]
    Change from baseline of relative hepatic mitochondrial flux will be assessed with an oral glycerol stable isotope tracer and subsequent blood draws while fasting. The outcome will be the relative proportion of hepaticly secreted glucose and glycerol that has undergone label rearrangement representative of excess mitochondrial metabolism - termed % indirect.

Information from the National Library of Medicine

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Ages Eligible for Study:   12 Years to 21 Years   (Child, Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No

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

Exclusion Criteria:

  1. Diagnosed with or have a family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2).
  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.
  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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT03919929

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Contact: Melanie Cree-Green, MD, PhD 720-777-6128 MELANIE.GREEN@UCDENVER.EDU
Contact: Yesenia Garcia-Reyes, MS 720-777-6984

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United States, Colorado
University of Colorado Anshutz Medical Campus/Children's Hospital Colorado
Aurora, Colorado, United States, 80045
Sponsors and Collaborators
University of Colorado, Denver
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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Principal Investigator: Melanie Cree-Green, MD, PhD Children's Hospital Colorado

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Responsible Party: University of Colorado, Denver Identifier: NCT03919929     History of Changes
Other Study ID Numbers: 19-0636
1R01DK120612-01A1 ( U.S. NIH Grant/Contract )
First Posted: April 18, 2019    Key Record Dates
Last Update Posted: September 26, 2019
Last Verified: September 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Colorado, Denver:
Insulin Resistance
Additional relevant MeSH terms:
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Pediatric Obesity
Nutrition Disorders
Body Weight
Signs and Symptoms
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Obesity Agents
Hormones, Hormone Substitutes, and Hormone Antagonists