search
Back to results

Assessing the Impact of Contraceptives on Bone Health Using 41Ca

Primary Purpose

Other Disorders of Bone Development and Growth

Status
Active
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Combined Oral Contraceptive (COC)
Contraceptive Vaginal Ring (CVR)
Sponsored by
Penn State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Other Disorders of Bone Development and Growth focused on measuring Calcium Tracer, Oral Contraceptives, Contraceptive Vaginal Ring, Impact of contraceptives on bone health using 41Ca

Eligibility Criteria

18 Years - 25 Years (Adult)FemaleAccepts Healthy Volunteers

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).

Sites / Locations

  • Women's Health and Exercise Laboratories, The Pennsylvania State University

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Combined Oral Contraceptive (COC)

Contraceptive Vaginal Ring (CVR)

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Changes in 41Ca:Ca ratio
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

Changes in serum concentrations of insulin-like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP-1, IGFBP-3), and acid labile subunit (ALS)
Changes in fasting serum concentrations of IGF-1, IGFBP-1, IGFBP-3, and ALS after oral and non-oral contraceptive therapy
Changes in serum concentrations of markers of bone formation and bone resorption
Changes in fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (CTx) after oral and non-oral contraceptive therapy

Full Information

First Posted
January 27, 2015
Last Updated
March 29, 2023
Sponsor
Penn State University
Collaborators
Purdue University
search

1. Study Identification

Unique Protocol Identification Number
NCT02367846
Brief Title
Assessing the Impact of Contraceptives on Bone Health Using 41Ca
Official Title
The Effect of Oral vs. Non-oral Contraceptive Therapy on Bone Turnover Using 41Ca Methodology
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
January 2015 (undefined)
Primary Completion Date
December 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Penn State University
Collaborators
Purdue University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Other Disorders of Bone Development and Growth
Keywords
Calcium Tracer, Oral Contraceptives, Contraceptive Vaginal Ring, Impact of contraceptives on bone health using 41Ca

7. Study Design

Primary Purpose
Basic Science
Study Phase
Phase 4
Interventional Study Model
Crossover Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
6 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Combined Oral Contraceptive (COC)
Arm Type
Experimental
Arm Description
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.
Arm Title
Contraceptive Vaginal Ring (CVR)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Combined Oral Contraceptive (COC)
Other Intervention Name(s)
Apri (Reclipsen)
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Contraceptive Vaginal Ring (CVR)
Other Intervention Name(s)
Nuva Ring
Intervention Description
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.
Primary Outcome Measure Information:
Title
Changes in 41Ca:Ca ratio
Description
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
Time Frame
49 days of contraceptive therapy
Secondary Outcome Measure Information:
Title
Changes in serum concentrations of insulin-like growth factor-1 (IGF-1), IGF-binding proteins (IGFBP-1, IGFBP-3), and acid labile subunit (ALS)
Description
Changes in fasting serum concentrations of IGF-1, IGFBP-1, IGFBP-3, and ALS after oral and non-oral contraceptive therapy
Time Frame
49 days of contraceptive therapy
Title
Changes in serum concentrations of markers of bone formation and bone resorption
Description
Changes in fasting serum concentrations of markers of bone formation (osteocalcin, P1NP) and bone resorption (CTx) after oral and non-oral contraceptive therapy
Time Frame
49 days of contraceptive therapy

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
25 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mary Jane De Souza, PhD
Organizational Affiliation
Penn State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Women's Health and Exercise Laboratories, The Pennsylvania State University
City
University Park
State/Province
Pennsylvania
ZIP/Postal Code
16802
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
21343758
Citation
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.
Results Reference
background
PubMed Identifier
21152905
Citation
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.
Results Reference
background
PubMed Identifier
19584189
Citation
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.
Results Reference
background
PubMed Identifier
17033771
Citation
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.
Results Reference
background

Learn more about this trial

Assessing the Impact of Contraceptives on Bone Health Using 41Ca

We'll reach out to this number within 24 hrs