Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial MMPs

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01469585
Recruitment Status : Unknown
Verified August 2014 by Bliss Kaneshiro, University of Hawaii.
Recruitment status was:  Active, not recruiting
First Posted : November 10, 2011
Last Update Posted : August 19, 2014
Charles Drew University of Medicine and Science
Meharry Medical College
Information provided by (Responsible Party):
Bliss Kaneshiro, University of Hawaii

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 Not Applicable

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.

MMPs, 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 MMPs in endometrial biopsy (EMB) 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 Type : Interventional  (Clinical Trial)
Estimated Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Oral Contraceptives and Subantimicrobial Doxycycline: Effect on Endometrial MMPs
Study Start Date : November 2011
Actual Primary Completion Date : June 2012
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

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 Name: Oracea

No Intervention: Continuous Oral Contraceptive Pill
Women will take only the continuous oral contraceptive.

Primary Outcome Measures :
  1. Determine the effect of combined oral contraceptives on endometrial MMP expression. [ Time Frame: 49 days ]
    Baseline MMP expression will be determined on day 19-21 of cycle 1. During cycle 2, when women are taking the cyclic oral contraceptive, the EMB will be performed between cycle day 19-21 (study day 47-49), prior to endometrial degradation.

Secondary Outcome Measures :
  1. Determine the effect of sub-antimicrobial doxycycline on MMP expression and activity in continuous oral contraceptive users. [ Time Frame: 84 days ]
    Based on doxycycline's action as an MMP inhibitor, it is hypothesized that MMP expression and activity will be decreased in women taking sub-antimicrobial doxycycline compared to women on continuous oral contraceptives only. Because it is expensive to take sub-antimicrobial doxycycline for longer than 28 days, if it is to be clinically useful, it should have an appreciable effect on endometrial MMP levels after 28 days.

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
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 EE and LNG;
  • Women who are pregnant, breastfeeding or have POS;
  • 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.

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 identifier (NCT number): NCT01469585

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

Responsible Party: Bliss Kaneshiro, Assistant Professor, University of Hawaii Identifier: NCT01469585     History of Changes
Other Study ID Numbers: UH DOXY RTRN
First Posted: November 10, 2011    Key Record Dates
Last Update Posted: August 19, 2014
Last Verified: August 2014

Keywords provided by Bliss Kaneshiro, University of Hawaii:
continuous oral contraceptives
MMP expression

Additional relevant MeSH terms:
Uterine Hemorrhage
Uterine Diseases
Genital Diseases, Female
Pathologic Processes
Contraceptive Agents
Contraceptives, Oral
Contraceptives, Oral, Combined
Reproductive Control Agents
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antiprotozoal Agents
Antiparasitic Agents
Contraceptive Agents, Female