Norplant and Irregular Bleeding/Spotting - Full Text View

Purpose

Irregular or prolonged menstrual bleeding and/or spotting are common side effects in patients using progestin-only hormonal contraception such as levonorgestrel implants (Norplant). Doxycycline, a drug approved by the Food and Drug Administration (FDA) to treat gum disease, may reduce the occurrence of uterine bleeding and spotting in women who use Norplant. This study will evaluate the effects of doxycycline on uterine bleeding/spotting in women using Norplant.

Condition	Intervention	Phase
Endometrial Bleeding Periodontal Disease	Drug: doxycycline	Phase IV

Drug Information available for:

Doxycycline Doxycycline calcium Doxycycline hyclate Levonorgestrel

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Factorial Assignment, Safety/Efficacy Study

Official Title:	A Prospective Randomized Clinical Trial of Doxycycline 20mg Twice a Day Versus Placebo on the Bleeding and Spotting in Women After Insertion of a Levonorgestrel Implant (Norplant) Protocol #2002-1

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Estimated Enrollment:	50
Study Start Date:	February 2003
Estimated Study Completion Date:	February 2005

Detailed Description:

A high percentage of women using progestin-only contraception experience breakthrough bleeding (BTB) and spotting that causes impaired lifestyle and results in decreased compliance with this contraceptive method. There is a need for an effective, low-cost, easily adapted treatment to reduce the bleeding and spotting in progestin-only contraceptives. The molecular environment of the endometrium of women with BTB and spotting contains abnormally high levels of pro-inflammatory cytokines (TNF-alpha and IL-1 beta) and abnormally high levels of proteases (matrix metalloproteinases [MMPs] and neutrophil elastase), which prevent normal tissue repair. Doxycycline (DOX) is an inexpensive, FDA approved antibiotic that inhibits MMPs and reduces nitric oxide synthesis. This study will evaluate DOX treatment of progestin-only contraceptive induced BTB and spotting, characterize the endometrial molecular biologic changes that occur in DOX treated patients, and determine the effect of Norplant on sexual functioning and testosterone levels.

All participants in this study will receive Norplant. Participants will then be randomized to receive either DOX (20 mg twice a day) or placebo for 6 months. Participants will have 9 study visits during the 24 weeks of the study. Study visits will include a medical history, physical exam, and blood and urine tests. Participants will also have three periodontal evaluations and three endometrial biopsies. At the end of the study, participants may choose to have the Norplant implant removed if they wish to discontinue Norplant use; otherwise the implant may remain in for up to 5 years.

Eligibility

Ages Eligible for Study:	18 Years to 40 Years
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria

Regular menstrual periods for the last 2 cycles
Currently not using hormonal contraceptives, including oral contraceptives, patch, ring, or Norplant in 2 months prior to study entry, or Depo-Provera in 12 months prior to study entry
Currently not using tetracycline-class antibiotics
Normal Pap smear

Exclusion criteria

Pregnancy or breastfeeding within 2 months of study entry
Chronic migraine headaches
Uncontrolled high blood pressure
Untreated sexually transmitted diseases
Alcoholism or drug abuse within 12 months of study entry
Insulin dependent diabetes
Liver, kidney, or gallbladder disease
Participation in another clinical trial within 30 days of study entry
History of cancer
History of blood clots, strokes, or heart disease

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00064766

Locations


United States, Virginia
	CONRAD Clinical Research Center, Eastern Virginia Medical School	Recruiting
	Norfolk, Virginia, United States, 23507
	Contact: Wendi A Gobhardt, RN, BSN 757-446-8487 gobharwa@evms.edu
	Contact: Joann Cooper, RN 757-446-8487 cooperjk@evms.edu
	Principal Investigator: David F Archer, MD
	Sub-Investigator: George Kovalevsky, MD
	Sub-Investigator: Susan A Ballagh, MD
	Sub-Investigator: Gayle McCombs, RHD, MS

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators


Principal Investigator:	David F Archer, MD	CONRAD Clinical Research Center, Eastern Virginia Medical School

More Information

Study ID Numbers:	R01HD43175, NIH 1 R01 HD43175-01
First Received:	July 11, 2003
Last Updated:	June 23, 2005
ClinicalTrials.gov Identifier:	NCT00064766
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Norplant

Periodontal disease

Endometrial bleeding

Progestin-induced endometrial bleeding

Study placed in the following topic categories:

Mouth Diseases

Periodontal Diseases

Metrorrhagia

Levonorgestrel

Stomatognathic Diseases

Hemorrhage

Doxycycline

Additional relevant MeSH terms:

Anti-Infective Agents

Antiprotozoal Agents

Contraceptive Agents

Contraceptives, Oral

Physiological Effects of Drugs

Contraceptive Agents, Female

Reproductive Control Agents

Pharmacologic Actions

Anti-Bacterial Agents

Antimalarials

Antiparasitic Agents

Pathologic Processes

Therapeutic Uses

Contraceptives, Oral, Synthetic

ClinicalTrials.gov processed this record on November 30, 2008

Sponsored by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00064766