- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02367833
Effects of Oral vs. Non-oral Contraceptives on the GH/IGF-1 Axis
Primary Mechanisms Underlying the Effects of Oral vs. Non-oral Contraceptives on the GH/IGF-1 Axis and Bone Metabolism in Young Women
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This study is a preclinical, multi-site trial (Penn State University and Purdue University) that will determine whether the negative effects of combined oral contraceptive (COC) therapy on bone turnover are dependent on the route of administration such that an attenuation of these effects is observed when a comparable dose of non-oral transdermal contraceptive (TDC) therapy and contraceptive vaginal ring (CVR) therapy are also tested. Millions of women use COC therapy for birth control purposes or regulation of menstrual cycles. TDC and CVR therapies are relatively new FDA-approved contraceptive alternatives to COC. The purpose of the proposed project is to address the potential mechanism(s) by which oral ethinyl estradiol (EE) may negatively impair bone via "first pass" effects on the liver and compare these effects to transdermally-administered and vaginally-administered EE in young women. We will assess mechanistic effects by way of 2-day serial sampling and by an insulin-like growth factor (IGF-1) generation test. The IGF-1 generation test was developed over 20 years ago and is currently used to diagnose growth hormone (GH) insensitivity. IGF-1 generation tests may also be used to amplify effects not observable by the assessment of fasting or serial concentrations of systemic IGF-1(secreted by the liver) and its associated binding proteins. This study will be the first study to examine the physiological mechanisms whereby the route of estrogen administration affects the GH/IGF-1 axis and bone turnover in young women.
The overall purpose of this study is to explore differences in liver metabolism and bone turnover of oral versus transdermal and vaginal contraceptive therapy. In an effort to expose the route-dependent effects of oral versus transdermal and vaginal contraceptive therapy on liver and bone metabolism, we will examine the effects of ethinyl estradiol on serially-assessed fasting concentrations of the GH/IGF-1 axis and bone turnover and explore physiological mechanisms underlying hepatic responsiveness to oral versus transdermal and vaginal contraceptive therapy using an IGF-1 Generation Test as a probe.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
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Pennsylvania
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University Park, Pennsylvania, United States, 16802
- Women's Health and Exercise Laboratories, The Pennsylvania State University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Female
- Age 18-30 yrs
- BMI 18-29 kg/m2
- Non-smoking
- Not using hormonal contraceptives for at least 6 months prior
- Not currently pregnant nor intending to become pregnant in the next 6 months
- Not lactating
- No apparent metabolic, endocrine, musculoskeletal, or severe psychiatric disease
- Willing to adhere to maintenance of current exercise training and diet and remain weight stable (±2 kg) during study
- Variable physical activity acceptable, but mode must be primarily weight bearing
- At least 9 menses in past 12 months
- Willing to quit taking any current nutritional supplements and take Calcium and Vitamin D supplements for the duration of the study.
- If 21 or older, a normal Pap smear must be confirmed.
Exclusion Criteria:
- Non-weight bearing exercise as primary mode of physical activity
- Known or suspected metabolic or endocrine disease
- Pregnant
- Currently consuming large amounts of soy products
- Regular consumption of grapefruit juice
- Current clinical eating disorder or other axis 1 psychiatric or bipolar disorders
- Oral or hormonal contraceptive use in the last 6 months
- Currently amenorrheic
- Hyperparathyroidism
- Liver or renal disease
- Evidence of malabsorption or skeletal disorder
- Thyroid abnormalities (controlled hypothyroidism acceptable)
- Chronic use of non-steroidal anti-inflammatory drugs (NSAIDS)
- Taking medications known to have interactions with contraceptive therapy
- Division I Athlete, on or off season
- Other Exclusion Criteria proposed by the World Health Organization COC Contraindications (Grossman, 2011)
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Combined Oral Contraceptives (COC)
Apri (or generic equivalent - Reclipsen) (30µg/d EE, 150 µg/d desogestrel) is a monophasic dosing regimen of 21 active and 7 placebo pills.
On Day 1 of the Intervention, participants in the COC group will begin taking the COC pill.
Each participant in this group will ingest active pills from the first pack each day for the first 21 days.
Pills ingested on days 22 through 28 are placebo pills.
A second pill pack will begin on day 29 and pills with active ingredients will be ingested from the second pack each day for days 29-49.
On day 50, the participants will immediately begin a 3rd pill pack, if the post-study testing is still occurring, and will ingest a pill with active ingredients from the third pack for days 50-56 (or for as long as the post-study testing is occurring).
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The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism.
Using a prospective repeated measures design, we will test the effects of 2 cycles of combined oral contraceptive (Apri or Reclipsen) on the GH/IGF-1 axis.
Other Names:
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Experimental: Transdermal Contraceptive (TDC)
Participants in the TDC group will apply a 20 cm2 patch (Xulane: 20µg/d EE,150µg/d norelgestromin) to the abdomen, upper arm or buttock.
The patch will be changed once weekly on the same day each week for weeks 1-3 (days 1-21, removed on day 22) and weeks 5-8 (days 29-56).
Week 4 (days 22-28) will be a patch-free week.
As soon as the post-study testing is complete, subjects will remove the patch.
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The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism.
Using a prospective repeated measures design, we will test the effects of 2 cycles of a transdermal contraceptive (Xulane) on the GH/IGF-1 axis.
Other Names:
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Experimental: Contraceptive Vaginal Ring (CVR)
Participants in the CVR group (NuvaRing - 15µg/d EE/120µg/d etonogestrel) will insert a vaginal ring into the vagina on Day 1 of the intervention.
The vaginal ring will be removed and discarded after 3 weeks of continuous use (days 1-21 of continuous use and removed on day 22).
There will be one week (days 22-28) that will be ring-free.
A new ring will be inserted for days 29-49.
On day 50, the second ring will be removed, and a third ring will be immediately inserted into the vagina (if the post-study testing is still occurring).
The third ring will remain in the vagina for the last week of the post-study period (days 50-56).
As soon as the post-study testing is complete, subjects will remove the ring.
|
The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral and non-oral ethinyl estradiol on the GH/IGF-1 axis and bone metabolism.
Using a prospective repeated measures design, we will test the effects of 2 cycles of vaginal ring contraceptive (Nuva Ring) on the GH/IGF-1 axis.
Other Names:
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No Intervention: Control Group
The Control group will complete all procedures with the exception of contraceptive therapy.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Insulin-like Growth Factor-1 (IGF-1), IGF Binding Proteins (IGFBP-1, IGFBP-3), and Acid Labile Subunit (ALS)
Time Frame: Baseline and post-49 days of contraceptive therapy
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Changes in serially-sampled fasting serum concentrations of insulin-like growth factor-1 (IGF-1) before and after 49 days of contraceptive therapy.
Data were only collected for IGF-1 levels, no assays were performed for IGFBP-1, IGFBP-3, and acid labile subunit (ALS) and no raw data were collected due to insufficient funds.
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Baseline and post-49 days of contraceptive therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Bone Turnover Markers
Time Frame: Baseline and post-49 days of contraceptive therapy
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Changes in serially-sampled fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (NTx, and CTx) before and after contraceptive therapy.
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Baseline and post-49 days of contraceptive therapy
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Changes in GH-stimulated IGF-1 Secretion
Time Frame: 49 days of contraceptive therapy
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Changes in IGF-1, IGFBP-1, IGFBP-3,and ALS in response to exogenously administered GH before and after contraceptive therapy.
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49 days of contraceptive therapy
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Mary Jane De Souza, PhD, The Pennsylvania State University
Publications and helpful links
General Publications
- Grossman D, White K, Hopkins K, Amastae J, Shedlin M, Potter JE. Contraindications to combined oral contraceptives among over-the-counter compared with prescription users. Obstet Gynecol. 2011 Mar;117(3):558-565. doi: 10.1097/AOG.0b013e31820b0244.
- Allaway HCM, Misra M, Southmayd EA, Stone MS, Weaver CM, Petkus DL, De Souza MJ. Are the Effects of Oral and Vaginal Contraceptives on Bone Formation in Young Women Mediated via the Growth Hormone-IGF-I Axis? Front Endocrinol (Lausanne). 2020 Jun 16;11:334. doi: 10.3389/fendo.2020.00334. eCollection 2020.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- STUDY00000053
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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