Oral Contraceptives and Body Mass Index

• Sponsor: Oregon Health and Science University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01170390
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)
• Enrollment: 32
• Location: 1
• Arms: 3
• Duration (Months): 27
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

The main hypothesis for this study is that increased Body Mass Index (BMI) alters oral contraceptive metabolism in a manner which results in decreased effectiveness in obese women.

Condition or Disease	Intervention/Treatment	Phase
Body Weight; Contraceptive Usage	Drug: All participants (Aviane); Drug: Portia; Drug: Aviane	Phase 4

Detailed Description

This study is being conducted to understand how effective oral hormonal birth control (the pill) is for women with high body mass index ("BMI" - the ratio of your height and weight BMI"). Previous studies of birth control traditionally do not include women above a certain BMI number, so safety and efficacy is not clearly understood in this population, yet the pill is still widely used in women with high BMI.

Reproductive-aged, ovulatory women of obese (BMI >30 kg/m2), will be placed on oral contraceptives for 2 months, then randomized into two intervention arms for an additional 2 months. At several key time points, synthetic steroid pharmacokinetics, gonadotropins (LH, FSH) and ovarian hormone levels (estradiol, progesterone), ovarian follicular activity by ultrasound monitoring, and cervical mucus testing will be monitored.

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Diagnostic
• Official Title: Improving Contraceptive Effectiveness in Obese Women
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Mar 1, 2011
• Actual Study Completion Date: Dec 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Other: All participants A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days).	Drug: All participants (Aviane); 20 mcg EE/0.1 mg LNG cyclically; Other Names: Levonorgestrel and Ethinyl Estradiol
Active Comparator: Aviane and Portia A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles	Drug: Portia; 30 mcg EE/0.15 mg LNG cyclically; Other Names: Levonorgestrel and Ethinyl Estradiol
Active Comparator: Aviane & Aviane A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	Drug: Aviane; 20 mcg EE/0.1 mg LNG continuously dosed; Other Names: Levonorgestrel and Ethinyl Estradiol

Outcome Measures

Primary Outcome Measures

1. LNG Steady State at Baseline and Then Post-randomization [baseline (2 months) and post-randomization (4 months)]

   The main goal is to test whether key pharmacokinetic parameters of levonordestrel (LNG) differ between obese women taking traditionally dosed OCs versus the interventional arms (i.e. using each obese subject as their own control).

Secondary Outcome Measures

1. LNG AUC [post-randomization (4 months)]

   Area under the curve post-randomization for levonorgestrel. AUC was calculated and extrapolated using post randomization in single daily samples drawn during Cycle 4 days 20-26. Serial repeat sampling to obtain a detailed PK curve was not performed to obtain this AUC. Subjects could provide samples during these days at times convenient to them and PK software accounted for the time between when the drug was dosed versus when the sample was drawn.

2. LNG AUC [baseline (2 months)]

   Baseline measurements of levonorgestrel AUC (on Aviane). Area under the curve at baseline for levonorgestrel. AUC was calculated from time zero to 168 hours and extrapolated to infinity from serial repeat sampling (0,0.5,1.1.5,2,3,4,6,8,12 hours and then single samples daily for 4 days between Cycles 1 and 2.

3. EE Steady State Baseline [Baseline (2 months)]

   Steady state levels of ethinyl estradiol (EE) at baseline (2 months)

4. EE Steady State After Randomization [Post-randomiziation 4 months]

   Steady state levels of ethinyl estradiol (EE) post- randomization

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 35 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Age 18-35

• BMI > 30kg/m2

• Proof of a normal breast and pelvic exam within last 9 months

• Self reported normal menstrual periods (24-35 days)

• Good general health

• In the investigator's opinion, are subject's veins suitable the repeat blood draws dictated by study protocol

• Single progesterone level during screening visit ≥ 3ng/mL

• Hematocrit ≥ 36%

Exclusion Criteria:

• Contradictions to COCs (history of deep vein thrombosis,myocardial infection, uncontrolled hypertension, pulmonary embolus, diabetes with vascular changes, stroke, migraines with neurologic changes, breast cancer, impaired liver function, uncontrolled thyroid disease, hypersensitivity or allergy to birth control)

• Smoker (must smoke 0 cigarettes)

• Actively seeking/involved in a weight loss program

• Currently pregnant/seeking pregnancy in the next 6 months

• Currently breast-feeding

• Past or current diagnosis of polycystic ovarian disease

• Recent use of birth control (Depot medroxyprogesterone: 6 months, Progestin implants: 6 months, Oral contraceptives, patch or ring: 2 months, Hormone impregnated IUD: 6 months)

• Currently taking medication that interferes with COC's (Rifampin, Carbamazepine, St. John's Wort)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Oregon Health and Science University	Portland	Oregon	United States	97239

Sponsors and Collaborators

• Oregon Health and Science University
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

• Principal Investigator: Alison Edelman, MD, MPH, Oregon Health and Science University

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• (OHSU Women's Health Research Unit)

Publications

None provided.

• Responsible Party: Alison Edelman, Associate Professor, Oregon Health and Science University
• ClinicalTrials.gov Identifier: NCT01170390
• Other Study ID Numbers: OHSU FAMPLAN 5382; R01HD061582
• First Posted: Jul 27, 2010
• Last Update Posted: Dec 31, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by Alison Edelman, Associate Professor, Oregon Health and Science University: Obesity; Body weight; Oral contraception; Efficacy
• Additional relevant MeSH terms: Body Weight; Estradiol 17 beta-cypionate; Estradiol 3-benzoate; Levonorgestrel; Ethinyl Estradiol; Ethinyl estradiol, levonorgestrel drug combination; Estradiol; Polyestradiol phosphate

Study Results

Participant Flow

Recruitment Details	A prospective cohort study was conducted at the Oregon Health & Science University (OHSU) in Portland, OR, from March 2006 to September 2007. Recruitment included print ads in local newspapers, flyers posted in the Center for Women's Health & other OHSU clinics and public places, and electronic postings to web sites such as Craig's List.

Arm/Group Title	All Participants	Study Arm #1 (Aviane and Aviane)	Study Arm #2 (Aviane and Portia)
Arm/Group Description	All participants were given a low dose oral contraceptive (Aviane) cyclically for 2 months	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Period Title: Oral Contraceptives
STARTED	32	0	0
COMPLETED	31	0	0
NOT COMPLETED	1	0	0
Period Title: Oral Contraceptives
STARTED	0	17	15
COMPLETED	0	16	15
NOT COMPLETED	0	1	0

Baseline Characteristics

Arm/Group Title	Aviane and Aviane	Aviane and Portia	Total
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles	Total of all reporting groups
Overall Participants	16	15	31
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	16 100%	15 100%	31 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	30 (4)	27 (4)	29 (4.7)
Sex: Female, Male (Count of Participants)
Female	16 100%	15 100%	31 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	16 100%	15 100%	31 100%

Outcome Measures

1. Primary Outcome

Title	LNG Steady State at Baseline and Then Post-randomization
Description	The main goal is to test whether key pharmacokinetic parameters of levonordestrel (LNG) differ between obese women taking traditionally dosed OCs versus the interventional arms (i.e. using each obese subject as their own control).
Time Frame	baseline (2 months) and post-randomization (4 months)

Outcome Measure Data

Analysis Population Description

One subject discontinued prior to the completion of the baseline studies in the Aviane/Aviane arm

Arm/Group Title	Aviane & Aviane	Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Measure Participants	16	15
LNG steady state levels at baseline	3.82 (1.28)	3.13 (0.87)
After randomization (4 months)	3.01 (0.19)	3.58 (0.35)

2. Secondary Outcome

Title	LNG AUC
Description	Area under the curve post-randomization for levonorgestrel. AUC was calculated and extrapolated using post randomization in single daily samples drawn during Cycle 4 days 20-26. Serial repeat sampling to obtain a detailed PK curve was not performed to obtain this AUC. Subjects could provide samples during these days at times convenient to them and PK software accounted for the time between when the drug was dosed versus when the sample was drawn.
Time Frame	post-randomization (4 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aviane & Aviane	Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Measure Participants	16	15
Mean (Standard Deviation) [hr*ng/mL]	412 (255)	283 (130)

3. Secondary Outcome

Title	LNG AUC
Description	Baseline measurements of levonorgestrel AUC (on Aviane). Area under the curve at baseline for levonorgestrel. AUC was calculated from time zero to 168 hours and extrapolated to infinity from serial repeat sampling (0,0.5,1.1.5,2,3,4,6,8,12 hours and then single samples daily for 4 days between Cycles 1 and 2.
Time Frame	baseline (2 months)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aviane and Aviane	Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Measure Participants	16	15
Mean (Standard Deviation) [hr*ng/mL]	267 (115)	199 (75)

4. Secondary Outcome

Title	EE Steady State Baseline
Description	Steady state levels of ethinyl estradiol (EE) at baseline (2 months)
Time Frame	Baseline (2 months)

Outcome Measure Data

Analysis Population Description

One subject discontinued prior to the completion of the baseline cycle in the Aviane/Aviane arm

Arm/Group Title	Aviane & Aviane	Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Measure Participants	16	15
Mean (Standard Deviation) [ng/mL]	0.12 (0.04)	0.1 (0.03)

5. Secondary Outcome

Title	EE Steady State After Randomization
Description	Steady state levels of ethinyl estradiol (EE) post- randomization
Time Frame	Post-randomiziation 4 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aviane & Aviane	Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)	A low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
Measure Participants	16	15
Mean (Standard Deviation) [ng/mL]	0.08 (0.08)	0.11 (0.01)

Adverse Events

Arm/Group Title	Aviane and Aviane		Aviane and Portia
Arm/Group Description	A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A very-low dose oral contraceptive given continuously for 56 days (20mcg EE component, 28 days of active pills/cycle with no hormone free interval)		A very-low dose oral contraceptive given cyclically (21 days of active pills/cycle with a 7 day hormonal-free interval) for 2 cycles (56 days). A low dose oral contraceptive given cyclically (30mcg EE component, 21 days of active pills/cycle with a 7 day hormonal-free interval) for two cycles
All Cause Mortality
	Aviane and Aviane		Aviane and Portia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aviane and Aviane		Aviane and Portia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)
Other (Not Including Serious) Adverse Events
	Aviane and Aviane		Aviane and Portia
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/16 (0%)		0/15 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.