Effect of a Commonly Used Antibiotic, Doxycycline, in Women With Polycystic Ovarian Syndrome (MI-PCOS)

The Use of an MMP Inhibitor, Doxycycline, to Reduce Ovarian Androgen Production and Restore Normal Cycling in Women With Polycystic Ovarian Syndrome

The purpose of this study is to study the effect of a commonly used antibiotic, doxycycline, on the production of ovarian hormones and menstrual cycles in women with Polycystic Ovarian Syndrome (PCOS).

Study Overview

• Status: Completed
• Conditions: Androgen Excess; Polycystic Ovarian Syndrome (PCOS); Irregular Menstrual Cycles
• Intervention / Treatment: Drug: doxycycline; Other: Sugar Pill

Detailed Description

Polycystic ovarian syndrome (PCOS) is one of the leading causes of female infertility, affecting 5-10% of reproductive-age women . This heterogeneous disorder is characterized by anovulatory infertility, androgen excess, an increase in the ratio of LH to FSH, and morphologic polycystic changes to the ovaries. Obesity and insulin resistance are also metabolic factors associated with PCOS that further increase the morbidity in these patients. Inducing fertility in patients with PCOS can be a challenge, as it most often involves ovulation induction that can lead to ovarian enlargement, hyperstimulation, and multiple-birth pregnancies. This study is designed to determine novel effective strategies to promote normal cycling in this patient population.

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • New York
    • Rochester, New York, United States, 14623
      • University of Rochester, Strong Fertility Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Women between 18 and 40 years of age.
2. History of PCOS with < 8 periods the proceeding year
3. Clinical or biochemical evidence of androgen excess
4. BMI <40
5. Willingness to sign consent for study including participation with collection of blood specimens
6. Willingness to discontinue OCP for duration of study period up to 36 weeks

Exclusion Criteria:

1. Pregnancy
2. Hypersensitivity to doxycycline or tetracycline
3. History of Cushing's syndrome
4. History of hyperprolactinemia
5. History of congenital adrenal hyperplasia
6. Significant hepatic impairment, including serum AST or ALT >1.5 times upper limits of normal.
7. Significant renal impairment, GFR <60 ml/min
8. Current use of metformin, statins, glucocorticoids, spironolactone and/or anti-estrogens.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Doxycycline; Subjects randomized to receive doxycycline for a period of 12 weeks. A 12-week period thereafter will occur off study medication. The dose of doxycycline to be used in this study is 200mg/day in divided doses of 100mg twice daily. The dose of doxycycline being used in this study is 100mg because it is the standard approved dose.	Drug: doxycycline; 200mg/day in divided doses of 100mg twice daily
Placebo Comparator: Sugar Pill; The administered placebo is to be continued for a period of 12 weeks. A 12-week period thereafter will occur off placebo control	Other: Sugar Pill; 1 pill twice a day; Other Names: Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total Serum Testosterone	We will determine total serum testosterone levels in all participating subjects at week 24.	24 weeks
Total Serum Testosterone	We will determine total serum testosterone levels in all participating subjects at week 12.	week 12

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serum Progesterone Levels in Blood	Serum progesterone levels will be obtained on a weekly basis to assess ovulation. We will then perform statistical analysis on this data to determine the effectiveness of doxycycline in this study population.	24 weeks
Free Testosterone in Serum		week 12
Free Testosterone in Serum		week 24
Serum Hormone Binding Globulin (SHBG)		week 12
Serum Hormone Binding Globulin (SHBG)		week 24
Total Number of Ovulations	The total number of ovulations per group. Ovulation was defined as elevation of serum progesterone and or urinary pregnanediol glucuronide followed by documented menstrual bleeding within 2 weeks of elevation.	week 24

Collaborators and Investigators

• Sponsor: University of Rochester
• Investigators: Principal Investigator: Kathleen M Hoeger, MD, MPH, University of Rochester; Principal Investigator: Stephen Hammes, MD, University of Rochester

Study record dates

Study Major Dates

• Study Start: November 1, 2010
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: August 11, 2011
• First Submitted That Met QC Criteria: February 7, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): January 13, 2016
• Last Update Submitted That Met QC Criteria: December 9, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Polycystic Ovarian Syndrome; Irregular Menstrual Cycles; Androgen Excess in Women
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms; Endocrine System Diseases; Disease; Ovarian Cysts; Cysts; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; 46, XX Disorders of Sex Development; Disorders of Sex Development; Urogenital Abnormalities; Adrenogenital Syndrome; Congenital Abnormalities; Polycystic Ovary Syndrome; Hyperandrogenism; Syndrome; Anti-Infective Agents; Anti-Bacterial Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Doxycycline
• Other Study ID Numbers: RSRB 00034479