- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02367846
Assessing the Impact of Contraceptives on Bone Health Using 41Ca
The Effect of Oral vs. Non-oral Contraceptive Therapy on Bone Turnover Using 41Ca Methodology
Study Overview
Status
Intervention / Treatment
Detailed Description
This study is a preclinical, multi-site study (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 contraceptive therapy, such as vaginal contraceptive (CVR) therapy is also tested. Millions of women use COC therapy for birth control purposes or regulation of menstrual cycles. CVR therapy is a relatively new FDA-approved contraceptive alternative to COC. The purpose of the proposed project is to investigate whether oral ethinyl estradiol (EE) may negatively impair bone turnover when compared to vaginally-administered EE in young physically-active women.
A novel calcium tracer technology suitable to rapidly assess changes in net bone calcium balance in a small sample size will be applied to evaluate the effects of COC and CVR therapy on bone turnover. The radioisotope Calcium-41 (41Ca) demonstrates increased sensitivity when compared to dual x-ray absorptiometry (DXA) and increased specificity for bone mineralization and precision when compared to biochemical markers of bone turnover. This study will be the first study to examine how the route of estrogen administration affects bone turnover in young physically active women by assessing changes in net bone calcium balance with different forms of contraceptive therapy.
The overall purpose of this study is to explore the effects of oral versus vaginal contraceptive therapy on bone turnover in young exercising women using 41Ca technology. In an effort to expose the route-dependent effects of oral versus non-oral contraceptive therapy on bone turnover, the investigators will examine 1) the effects of ethinyl estradiol on bone calcium balance using the 41Ca technology and 2) the underlying physiological mechanisms associated with the effects of oral versus vaginal contraceptive therapy on net bone calcium balance.
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
Description
Inclusion Criteria:
- Female
- Age 18-25 yrs
- BMI 18-29 kg/m2
- Non-smoking
- Willing to refrain from using hormonal contraceptives for the equilibration + baseline period of the study (~150 days)
- Availability to frequently visit the laboratory in the next 12 months
- Not currently pregnant nor intending to become pregnant in the next 12 months
- Not lactating
- No apparent metabolic, endocrine, musculoskeletal, or severe psychiatric disease
- Willing to maintain consistent exercise (aerobic, weight-bearing) and dietary habits during pre-intervention and intervention periods
- Willing to refrain from supplements other than those provided by study staff in the next 12 months
- Variable physical activity acceptable, but mode must be primarily weight bearing
- At least 9 menses in the past 12 months
Exclusion Criteria:
- Non-weight bearing exercise as primary mode of physical activity
- Resistance exercise training (≥ 2 times 30 minutes per week of resistance exercise)
- Complete seasonal change of impact mode of physical activity
- Known or suspected metabolic or endocrine disease
- Smoking
- Pregnant
- Currently consuming large amounts of soy products
- Current clinical eating disorder or other axis 1 psychiatric disorder or bipolar disorders
- Oral or hormonal contraceptive use in the last 6 months
- 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 oral or vaginal contraceptive therapy
- Other Exclusion Criteria proposed by the World Health Organization COC Contraindications (Grossman et al., 2011).
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: Combined Oral Contraceptive (COC)
We are testing the effects of a COC (Apri (Reclipsen); 30 µg EE, 150 µg desogestrel).
On the first day of the intervention, the participants randomized to COC will begin taking the pill.
One pill will be ingested orally at the same time each day for days 1-49 of the intervention.
Pills ingested during days 1-21 and during days 29-49 will be active tablets.
Pills ingested on days 22-28 will be tablets without active ingredients.
Each participant in the COC group will ingest a pill from the first pack each day for the first 28 days then begin the second pack.
If a participant is unable to collect a 24-h urine sample on day 49, she will take active tablets from the third pill pack until she has collected the 24-h urine sample.
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The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral vs. non-oral ethinyl estradiol on net bone calcium balance.
A prospective crossover study with repeated measures and a simple random assignment will be used to test the effects of 49 days of COC use on bone metabolism using 41Ca to determine net bone calcium balance.
Subjects will be randomized to receive COC during either the first or second intervention period.
Other Names:
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Experimental: Contraceptive Vaginal Ring (CVR)
We are testing the effects of the vaginal ring (Nuva Ring; 15 µg/d EE, 120 µg/d etonogestrel).
When randomized to CVR, participants will insert the contraceptive ring into their vagina .
The ring will be worn during weeks 1-3, and again during weeks 5-7.
During week 4, no ring will be worn to allow for withdrawal bleeding.
If a participant is unable to collect a 24-h urine sample on day 49, they will insert a third ring which will remain in the vagina until she has collected a 24-h urine sample.
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The proposed study is a preclinical, multi-site trial comparing the short-term effects of oral vs. non-oral ethinyl estradiol on net bone calcium balance.
A prospective crossover study with repeated measures and a simple random assignment will be used to test the effects of 49 days of CVR use on bone metabolism using 41Ca to determine net bone calcium balance.
Subjects will be randomized to receive CVR during either the first or second intervention period.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Changes in 41Ca:Ca ratio
Time Frame: 49 days of contraceptive therapy
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Changes in the 41Ca:Ca ratio in 24-h urine samples measured every 10-14 days during and after oral and non-oral contraceptive therapy as determined by Accelerometer Mass Spectrometry
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49 days of contraceptive therapy
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in serum concentrations of insulin-like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP-1, IGFBP-3), and acid labile subunit (ALS)
Time Frame: 49 days of contraceptive therapy
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Changes in fasting serum concentrations of IGF-1, IGFBP-1, IGFBP-3, and ALS after oral and non-oral contraceptive therapy
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49 days of contraceptive therapy
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Changes in serum concentrations of markers of bone formation and bone resorption
Time Frame: 49 days of contraceptive therapy
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Changes in fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (CTx) after oral and non-oral contraceptive therapy
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49 days of contraceptive therapy
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Mary Jane De Souza, PhD, Penn 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.
- Denk E, Hillegonds D, Vogel J, Synal A, Geppert C, Wendt K, Fattinger K, Hennessy C, Berglund M, Hurrell RF, Walczyk T. Labeling the human skeleton with 41Ca to assess changes in bone calcium metabolism. Anal Bioanal Chem. 2006 Nov;386(6):1587-602. doi: 10.1007/s00216-006-0795-5. Epub 2006 Oct 11.
- Lee WH, Wastney ME, Jackson GS, Martin BR, Weaver CM. Interpretation of 41Ca data using compartmental modeling in post-menopausal women. Anal Bioanal Chem. 2011 Feb;399(4):1613-22. doi: 10.1007/s00216-010-4454-5. Epub 2010 Dec 9.
- Weaver CM, Martin BR, Jackson GS, McCabe GP, Nolan JR, McCabe LD, Barnes S, Reinwald S, Boris ME, Peacock M. Antiresorptive effects of phytoestrogen supplements compared with estradiol or risedronate in postmenopausal women using (41)Ca methodology. J Clin Endocrinol Metab. 2009 Oct;94(10):3798-805. doi: 10.1210/jc.2009-0332. Epub 2009 Jul 7.
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
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
- STUDY00000464
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