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Assessing the Impact of Contraceptives on Bone Health Using 41Ca

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ClinicalTrials.gov Identifier: NCT02367846
Recruitment Status : Active, not recruiting
First Posted : February 20, 2015
Last Update Posted : January 18, 2020
Sponsor:
Collaborator:
Purdue University
Information provided by (Responsible Party):
Mary Jane DeSouza, Penn State University

Brief Summary:
This preclinical randomized crossover study will examine the effects of oral versus non-oral contraceptive therapy on bone turnover in young exercising women. 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 non-oral contraceptive therapy on net bone calcium balance.

Condition or disease Intervention/treatment Phase
Other Disorders of Bone Development and Growth Drug: Combined Oral Contraceptive (COC) Drug: Contraceptive Vaginal Ring (CVR) Phase 4

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Basic Science
Official Title: The Effect of Oral vs. Non-oral Contraceptive Therapy on Bone Turnover Using 41Ca Methodology
Study Start Date : January 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Combined Oral Contraceptive (COC)
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 Name: Apri (Reclipsen)

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.
Drug: Contraceptive Vaginal Ring (CVR)
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 Name: Nuva Ring




Primary Outcome Measures :
  1. Changes in 41Ca:Ca ratio [ Time Frame: 49 days of contraceptive therapy ]
    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


Secondary Outcome Measures :
  1. 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 ]
    Changes in fasting serum concentrations of IGF-1, IGFBP-1, IGFBP-3, and ALS after oral and non-oral contraceptive therapy

  2. Changes in serum concentrations of markers of bone formation and bone resorption [ Time Frame: 49 days of contraceptive therapy ]
    Changes in fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (CTx) after oral and non-oral contraceptive therapy



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 25 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Female
  2. Age 18-25 yrs
  3. BMI 18-29 kg/m2
  4. Non-smoking
  5. Willing to refrain from using hormonal contraceptives for the equilibration + baseline period of the study (~150 days)
  6. Availability to frequently visit the laboratory in the next 12 months
  7. Not currently pregnant nor intending to become pregnant in the next 12 months
  8. Not lactating
  9. No apparent metabolic, endocrine, musculoskeletal, or severe psychiatric disease
  10. Willing to maintain consistent exercise (aerobic, weight-bearing) and dietary habits during pre-intervention and intervention periods
  11. Willing to refrain from supplements other than those provided by study staff in the next 12 months
  12. Variable physical activity acceptable, but mode must be primarily weight bearing
  13. At least 9 menses in the past 12 months

Exclusion Criteria:

  1. Non-weight bearing exercise as primary mode of physical activity
  2. Resistance exercise training (≥ 2 times 30 minutes per week of resistance exercise)
  3. Complete seasonal change of impact mode of physical activity
  4. Known or suspected metabolic or endocrine disease
  5. Smoking
  6. Pregnant
  7. Currently consuming large amounts of soy products
  8. Current clinical eating disorder or other axis 1 psychiatric disorder or bipolar disorders
  9. Oral or hormonal contraceptive use in the last 6 months
  10. Hyperparathyroidism
  11. Liver or renal disease
  12. Evidence of malabsorption or skeletal disorder
  13. Thyroid abnormalities (controlled hypothyroidism acceptable)
  14. Chronic use of non-steroidal anti-inflammatory drugs (NSAIDS)
  15. Taking medications known to have interactions with oral or vaginal contraceptive therapy
  16. Other Exclusion Criteria proposed by the World Health Organization COC Contraindications (Grossman et al., 2011).

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 ClinicalTrials.gov identifier (NCT number): NCT02367846


Locations
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United States, Pennsylvania
Women's Health and Exercise Laboratories, The Pennsylvania State University
University Park, Pennsylvania, United States, 16802
Sponsors and Collaborators
Penn State University
Purdue University
Investigators
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Principal Investigator: Mary Jane De Souza, PhD Penn State University
Publications:
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Responsible Party: Mary Jane DeSouza, Professor of Kinesiology and Physiology, Penn State University
ClinicalTrials.gov Identifier: NCT02367846    
Other Study ID Numbers: STUDY00000464
First Posted: February 20, 2015    Key Record Dates
Last Update Posted: January 18, 2020
Last Verified: January 2020
Keywords provided by Mary Jane DeSouza, Penn State University:
Calcium Tracer
Oral Contraceptives
Contraceptive Vaginal Ring
Impact of contraceptives on bone health using 41Ca
Additional relevant MeSH terms:
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Bone Diseases
Bone Diseases, Developmental
Musculoskeletal Diseases
Contraceptive Agents
Contraceptives, Oral
Contraceptives, Oral, Combined
Reproductive Control Agents
Physiological Effects of Drugs
Contraceptive Agents, Female