Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS (RING-PCOS)
Primary Purpose
Polycystic Ovary Syndrome
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Etonogestrel/ethinyl estradiol vaginal ring
Sponsored by
About this trial
This is an interventional prevention trial for Polycystic Ovary Syndrome
Eligibility Criteria
Inclusion Criteria:
- Diagnosis of PCOS according to Rotterdam criteria, with at least 2 of 3 of the following criteria: oligomenorrhea (≤8 periods per year), clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound
- Body mass index ≥25 and ≤45 kg/m2
- In good general health according to the investigators' discretion
- Willing to avoid pregnancy for the duration of the study
Exclusion Criteria:
- Current pregnancy or desire for pregnancy during course of study
- Current breastfeeding
- Second-trimester pregnancy within four weeks prior to initiation of NuvaRing or third-trimester pregnancy within 6 months prior to initiation of NuvaRing
- Use of hormonal contraception within four weeks prior to initiation of NuvaRing
- Diagnosis of metabolic syndrome. Metabolic syndrome will be defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL.
Contraindications to NuvaRing use:
- Age ≥ 35 plus tobacco use
- Current or past deep vein thrombosis or pulmonary embolism
- Cerebrovascular disease
- Coronary artery disease
- Thrombogenic valvular or rhythm diseases of the heart (such as subacute bacterial endocarditis with valvular disease or atrial fibrillation)
- Inherited or acquired coagulopathy
- Headaches with focal neurological symptoms or migraine headaches with aura
- Age ≥ 35 plus any migraine headaches
- Liver tumors, benign or malignant
- Undiagnosed abnormal uterine bleeding
- Current or past breast cancer or other estrogen- or progestin-sensitive cancer
- Hypersensitivity to any of the components of NuvaRing
- Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir
Medical comorbidities:
- 21-hydroxylase deficiency, congenital adrenal hyperplasia
- Untreated thyroid disease
- Untreated hyperprolactinemia
- Type 1 or 2 diabetes mellitus
- Uncontrolled liver disease
- Uncontrolled renal disease
- Current alcohol abuse
- Hypertension ≥ 140 mm Hg average systolic or ≥ 90 mm Hg average diastolic in women using anti-hypertensive medication
- Hypertension ≥ 150 mm Hg average systolic or ≥ 100 mm Hg average diastolic in women not using anti-hypertensive medication
- History of or current gynecologic cancer
- Triglycerides >=250 mg/dL
- Current use of lipid-lowering or weight loss agents
- Participation in any study of an investigational drug or device or biologic agent within 30 days
- Suspected adrenal or ovarian tumor secreting androgens
- Suspected Cushing's syndrome
- Bariatric surgery within 12 months
- Other medical concerns that in the judgment of the investigator may compromise safety of the participant or confound the reliability of compliance and information acquired in this study
Sites / Locations
- University of PennsylvaniaRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Contraceptive Ring
Arm Description
Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing), which releases 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily.
Outcomes
Primary Outcome Measures
Incidence of Metabolic Syndrome
Metabolic Syndrome defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL.
Secondary Outcome Measures
Change in low-density lipoprotein (LDL) measure
Change in high-density lipoprotein (HDL) measure
Change in triglycerides measure
Change in apolipoprotein A
Change in apolipoprotein B
Change in advanced lipid testing measure
Change in cholesterol efflux capacity
Change in fasting insulin level
Change in fasting 2 hour oral Glucose Tolerance Test result
Change in Testosterone
Change in Ferriman-Gallwey Hirsutism score
A lower score indicates less hirsutism. The F-G scoring system has a minimum value of 0, and a maximum value of 36.
Body Mass Index
Change in scoring on the Center for Epidemiologic Studies Depression Scale
The range of values is zero to 60, with the higher scores indicating the presence of more depressive symptoms.
Change in scoring on the State-Trait Anxiety Inventory
The State-Trait Anxiety Inventory measures both state and trait anxiety, the scores range from 20 to 80, with higher scores correlating with greater anxiety.
Change in scoring on Polycystic Ovary Syndrome Quality of Life Questionnaire
Worse quality of life is associated with a lower score on the questionnaire, with a range score from 30 to 210.
Full Information
NCT ID
NCT04257500
First Posted
January 31, 2020
Last Updated
September 19, 2023
Sponsor
Andrea Roe, MD, MPH
1. Study Identification
Unique Protocol Identification Number
NCT04257500
Brief Title
Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS
Acronym
RING-PCOS
Official Title
Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS
Study Type
Interventional
2. Study Status
Record Verification Date
September 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 24, 2020 (Actual)
Primary Completion Date
December 2023 (Anticipated)
Study Completion Date
December 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Andrea Roe, MD, MPH
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
Data Monitoring Committee
No
5. Study Description
Brief Summary
A prospective study to determine the metabolic effects of the contraceptive vaginal ring among overweight and obese women with polycystic ovary syndrome (PCOS). We will recruit a total of 40 participants and study use of the vaginal ring over a 4-month period.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
40 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Contraceptive Ring
Arm Type
Experimental
Arm Description
Etonogestrel/ethinyl estradiol vaginal ring (NuvaRing), which releases 120 mcg of etonogestrel and 15 mcg of ethinyl estradiol daily.
Intervention Type
Drug
Intervention Name(s)
Etonogestrel/ethinyl estradiol vaginal ring
Other Intervention Name(s)
NuvaRing
Intervention Description
16 weeks of continuous use of contraceptive vaginal ring
Primary Outcome Measure Information:
Title
Incidence of Metabolic Syndrome
Description
Metabolic Syndrome defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL.
Time Frame
4 months
Secondary Outcome Measure Information:
Title
Change in low-density lipoprotein (LDL) measure
Time Frame
4 months
Title
Change in high-density lipoprotein (HDL) measure
Time Frame
4 months
Title
Change in triglycerides measure
Time Frame
4 months
Title
Change in apolipoprotein A
Time Frame
4 months
Title
Change in apolipoprotein B
Time Frame
4 months
Title
Change in advanced lipid testing measure
Time Frame
4 months
Title
Change in cholesterol efflux capacity
Time Frame
4 months
Title
Change in fasting insulin level
Time Frame
4 months
Title
Change in fasting 2 hour oral Glucose Tolerance Test result
Time Frame
4 months
Title
Change in Testosterone
Time Frame
4 months
Title
Change in Ferriman-Gallwey Hirsutism score
Description
A lower score indicates less hirsutism. The F-G scoring system has a minimum value of 0, and a maximum value of 36.
Time Frame
4 months
Title
Body Mass Index
Time Frame
4 months
Title
Change in scoring on the Center for Epidemiologic Studies Depression Scale
Description
The range of values is zero to 60, with the higher scores indicating the presence of more depressive symptoms.
Time Frame
4 months
Title
Change in scoring on the State-Trait Anxiety Inventory
Description
The State-Trait Anxiety Inventory measures both state and trait anxiety, the scores range from 20 to 80, with higher scores correlating with greater anxiety.
Time Frame
4 months
Title
Change in scoring on Polycystic Ovary Syndrome Quality of Life Questionnaire
Description
Worse quality of life is associated with a lower score on the questionnaire, with a range score from 30 to 210.
Time Frame
4 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Diagnosis of PCOS according to Rotterdam criteria, with at least 2 of 3 of the following criteria: oligomenorrhea (≤8 periods per year), clinical or biochemical hyperandrogenism, and polycystic ovaries on ultrasound
Body mass index ≥25 and ≤45 kg/m2
In good general health according to the investigators' discretion
Willing to avoid pregnancy for the duration of the study
Exclusion Criteria:
Current pregnancy or desire for pregnancy during course of study
Current breastfeeding
Second-trimester pregnancy within four weeks prior to initiation of NuvaRing or third-trimester pregnancy within 6 months prior to initiation of NuvaRing
Use of hormonal contraception within four weeks prior to initiation of NuvaRing
Diagnosis of metabolic syndrome. Metabolic syndrome will be defined according to the updated Adult Treatment Panel III as 3 or more of the following criteria: blood pressure ≥130/85 mm Hg, waist circumference >35 inches, fasting glucose ≥110 mg/dL, TG ≥150 mg/dL, HDL-C <50 mg/dL.
Contraindications to NuvaRing use:
Age ≥ 35 plus tobacco use
Current or past deep vein thrombosis or pulmonary embolism
Cerebrovascular disease
Coronary artery disease
Thrombogenic valvular or rhythm diseases of the heart (such as subacute bacterial endocarditis with valvular disease or atrial fibrillation)
Inherited or acquired coagulopathy
Headaches with focal neurological symptoms or migraine headaches with aura
Age ≥ 35 plus any migraine headaches
Liver tumors, benign or malignant
Undiagnosed abnormal uterine bleeding
Current or past breast cancer or other estrogen- or progestin-sensitive cancer
Hypersensitivity to any of the components of NuvaRing
Use of hepatitis C drug combinations containing ombitasvir/paritaprevir/ritonavir
Medical comorbidities:
21-hydroxylase deficiency, congenital adrenal hyperplasia
Untreated thyroid disease
Untreated hyperprolactinemia
Type 1 or 2 diabetes mellitus
Uncontrolled liver disease
Uncontrolled renal disease
Current alcohol abuse
Hypertension ≥ 140 mm Hg average systolic or ≥ 90 mm Hg average diastolic in women using anti-hypertensive medication
Hypertension ≥ 150 mm Hg average systolic or ≥ 100 mm Hg average diastolic in women not using anti-hypertensive medication
History of or current gynecologic cancer
Triglycerides >=250 mg/dL
Current use of lipid-lowering or weight loss agents
Participation in any study of an investigational drug or device or biologic agent within 30 days
Suspected adrenal or ovarian tumor secreting androgens
Suspected Cushing's syndrome
Bariatric surgery within 12 months
Other medical concerns that in the judgment of the investigator may compromise safety of the participant or confound the reliability of compliance and information acquired in this study
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Andrea Morley
Phone
215-615-4202
Email
andrea.morley@pennmedicine.upenn.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea Roe, MD MPH
Organizational Affiliation
University of Pennsylvania
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Elizabeth Ruiz
Email
elizabeth.ruiz@pennmedicine.upenn.edu
First Name & Middle Initial & Last Name & Degree
Andrea Roe, MD, MPH
12. IPD Sharing Statement
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Does Vaginal Delivery of Combined Hormonal Contraception Affect the Risk of Metabolic Syndrome in Overweight/Obese Women With PCOS
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