Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial Matrix Metalloproteinases

• Sponsor: University of Hawaii (Other)
• Overall Status: Completed
• CT.gov ID: NCT01469585
• Collaborator: Charles Drew University of Medicine and Science (Other), Meharry Medical College (Other)
• Enrollment: 20
• Location: 1
• Arms: 2
• Duration (Months): 6
• Patients Per Site Per Month: 3.3

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the effects (good and bad) of subantimicrobial dose doxycycline on the irregular bleeding women experience when taking continuous oral contraceptive pills. This research is being done because currently, there is no effective treatment for this condition. Findings from this study could help to decrease the side effects of birth control pills and decrease unplanned pregnancies.

Condition or Disease	Intervention/Treatment	Phase
Breakthrough Bleeding	Drug: Doxycycline	N/A

Detailed Description

Continuous oral contraceptive administration entails women taking hormonally active pills for 28 days without a seven day placebo week to avoid hormonal withdrawal bleeding. Unfortunately, with continuous administration, timed, regular bleeding can be replace by irregular, unscheduled bleeding, which often leads to dissatisfaction, discontinuation and the possibility of unplanned pregnancy.

Matrix Metalloproteinases, a group of zinc-dependant proteases, are hypothesized to play a role in endometrial degradation. The purpose of this study is to describe the expression of Matrix Metalloproteinases in endometrial biopsy specimens collected 1) prior to initiating oral contraceptives 2) while taking cyclic oral contraceptive 3) while taking continuous oral contraceptives and 4) while taking continuous oral contraceptives along with sub-antimicrobial doxycycline.

Study Design

• Study Type: Interventional
• Actual Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial Matrix Metalloproteinases
• Study Start Date: Nov 1, 2011
• Actual Primary Completion Date: May 1, 2012
• Actual Study Completion Date: May 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Sub-antimicrobial doxycycline Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill.	Drug: Doxycycline; 40 mg orally at the start of cycle 3 (study day 57) for 28 days.; Other Names: Oracea
No Intervention: Continuous Oral Contraceptive Pill Women will take only the continuous oral contraceptive.

Outcome Measures

Primary Outcome Measures

1. Endometrial Matrix Metalloproteinase Expression by Gel Densitometry [49 days]

   Baseline Matrix Metalloproteinase expression (activity level) will be determined on day 19-21 of cycle 1. During cycle 2, when women are taking the cyclic oral contraceptive, the endometrial biopsy will be performed between cycle day 19-21 (study day 47-49), prior to endometrial degradation and activity level will be noted. Of note, the outcome is MMP activity level, not a change in level.

Secondary Outcome Measures

1. Matrix Metalloproteinase Expression and Activity by Gel Densitometry [84 days]

   Based on doxycycline's action as an Matrix Metalloproteinase inhibitor, it is hypothesized that Matrix Metalloproteinase expression and activity level will be decreased in women taking sub-antimicrobial doxycycline compared to women on continuous oral contraceptives only. The outcome is activity level (not a change in activity level)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 45 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Women between the ages 18 and 45 who are ovulatory as demonstrated by a pre-treatment Progesterone (P) greater than or equal to 3.0 ng/mL prior to oral contraceptive use

Exclusion Criteria:

• Women with any absolute contraindications to ethinyl estradiol and levonorgestrel;

• Women who are pregnant or breastfeeding

• Use of oral contraceptives, patch, ring, intrauterine or implantable hormonal contraception within 4-weeks;

• Medroxyprogesterone acetate use within six months;

• Current use of drugs that interfere with sex steroid metabolism.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii	United States	96826

Sponsors and Collaborators

• University of Hawaii
• Charles Drew University of Medicine and Science
• Meharry Medical College

Investigators

• Principal Investigator: Bliss Kaneshiro, MD, MPH, University of Hawaii John A. Burns School of Medicine Department of Obstetrics and Gynecology

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Bliss Kaneshiro, Assistant Professor, University of Hawaii
• ClinicalTrials.gov Identifier: NCT01469585
• Other Study ID Numbers: UH DOXY RTRN
• First Posted: Nov 10, 2011
• Last Update Posted: Dec 17, 2020
• Last Verified: Nov 1, 2020

• Keywords provided by Bliss Kaneshiro, Assistant Professor, University of Hawaii: continuous oral contraceptives; Matrix Metalloproteinase expression
• Additional relevant MeSH terms: Metrorrhagia; Doxycycline

Study Results

Participant Flow

Arm/Group Title	Sub-antimicrobial Doxycycline	Continuous Oral Contraceptive Pill
Arm/Group Description	Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill. Doxycycline: 40 mg orally at the start of cycle 3 (study day 57) for 28 days.	Women will take only the continuous oral contraceptive.
Period Title: Overall Study
STARTED	11	9
COMPLETED	4	6
NOT COMPLETED	7	3

Baseline Characteristics

Arm/Group Title	Active Comparator: Subantimicrobial Doxycycline	No Intervention: Continuous Oral Contraceptive Pill	Total
Arm/Group Description	Active comparator: Subantimicrobial doxycycline	No intervention: Continuous oral contraceptive pill	Total of all reporting groups
Overall Participants	11	9	20
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	11 100%	9 100%	20 100%
>=65 years	0 0%	0 0%	0 0%
Sex: Female, Male (Count of Participants)
Female	11 100%	9 100%	20 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	0 0%	0 0%	0 0%
Unknown or Not Reported	11 100%	9 100%	20 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 9.1%	0 0%	1 5%
Asian	2 18.2%	4 44.4%	6 30%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	1 9.1%	0 0%	1 5%
White	5 45.5%	2 22.2%	7 35%
More than one race	2 18.2%	3 33.3%	5 25%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	11 100%	9 100%	20 100%

Outcome Measures

1. Primary Outcome

Title	Endometrial Matrix Metalloproteinase Expression by Gel Densitometry
Description	Baseline Matrix Metalloproteinase expression (activity level) will be determined on day 19-21 of cycle 1. During cycle 2, when women are taking the cyclic oral contraceptive, the endometrial biopsy will be performed between cycle day 19-21 (study day 47-49), prior to endometrial degradation and activity level will be noted. Of note, the outcome is MMP activity level, not a change in level.
Time Frame	49 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sub-antimicrobial Doxycycline Group	Control
Arm/Group Description	Sub-antimicrobial doxycycline group (controlled release subantimicrobial doxycycyline 40 mg once daily)	Control (no medication)
Measure Participants	11	9
Mean (Standard Deviation) [relative expression]	1.33 (0.41)	2.49 (0.72)

2. Secondary Outcome

Title	Matrix Metalloproteinase Expression and Activity by Gel Densitometry
Description	Based on doxycycline's action as an Matrix Metalloproteinase inhibitor, it is hypothesized that Matrix Metalloproteinase expression and activity level will be decreased in women taking sub-antimicrobial doxycycline compared to women on continuous oral contraceptives only. The outcome is activity level (not a change in activity level)
Time Frame	84 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Sub-antimicrobial Doxycycline	Continuous Oral Contraceptive Pill
Arm/Group Description	Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill. Doxycycline: 40 mg orally at the start of cycle 3 (study day 57) for 28 days.	Women will take only the continuous oral contraceptive.
Measure Participants	4	6
Mean (Standard Deviation) [relative expression]	1.52 (0.63)	1.98 (0.87)

Adverse Events

Arm/Group Title	Sub-antimicrobial Doxycycline		Continuous Oral Contraceptive Pill
Arm/Group Description	Women will take sub-antimicrobial doxycyline in addition to the continuous oral contraceptive pill. Doxycycline: 40 mg orally at the start of cycle 3 (study day 57) for 28 days.		Women will take only the continuous oral contraceptive.
All Cause Mortality
	Sub-antimicrobial Doxycycline		Continuous Oral Contraceptive Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Sub-antimicrobial Doxycycline		Continuous Oral Contraceptive Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Sub-antimicrobial Doxycycline		Continuous Oral Contraceptive Pill
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT 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.