Clinical trial NCT00064766: Norplant and Irregular Bleeding/Spotting
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Endometrial Bleeding
Periodontal Disease
Keywords: Norplant
Periodontal disease
Endometrial bleeding
Progestin-induced endometrial bleeding
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor class: NIH
First posted: 2003-07-15
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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.

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 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Norfolk
country: United States
facility: CONRAD Clinical Research Center, Eastern Virginia Medical School
state: Virginia
Study officials:
affiliation: CONRAD Clinical Research Center, Eastern Virginia Medical School
name: David F Archer, MD
role: PRINCIPAL_INVESTIGATOR
References: