Official Title: “The Impact of GABA-Enhancing Agents on Cortical GABA Concentrations Across the Menstrual Cycle in Women”

The goal of this series of challenge studies is to examine the impact of menstrual cycle phase on cortical GABA response to administration of agents with either direct (benzodiazepines) or indirect (progesterone, fluoxetine) GABA modulating properties. While the impact of these agents on cortical GABA levels in women with premenstrual dysphoric disorder (PMDD) is of interest, this study is designed primarily for those women without a psychiatric illness.

Study Type: Interventional

Study Design: Other, Non-Randomized, Single Blind (Subject), Active Control, Single Group Assignment

Study Primary Completion Date: May 2010

Intervention(s) in this Clinical Trial

• Drug: Fluoxetine
  • Fluoxetine 20 mg by mouth in the follicular and luteal phase of the menstrual cycle per participant.
• Drug: Zolpidem
  • Zolpidem 10 mg by mouth in the follicular and luteal phase of the menstrual cycle per participant.
• Drug: Progesterone
  • Progesterone 800 mg by mouth will be administered to each participant once in the follicular and luteal phases of the menstrual cycle.

Arms, Groups and Cohorts in this Clinical Trial

• No Intervention: Zolpidem 1
  • Zolpidem will be administered twice to each participant; once in the follicular and luteal phases of the menstrual cycle.
• No Intervention: Progesterone 2
  • Progesterone will be administered twice to each participant; once in both the follicular and luteal phases of the menstrual cycle.
• No Intervention: Fluoxetine 3
  • Fluoxetine will be administered twice to each participant; once in both the follicular and luteal phases of the menstrual cycle.

Primary Measures

• To determine the impact of GABA-A receptor agonists (benzodiazepines, allopregnanolone) and other GABA-modulating agents (fluoxetine) on cortical GABA levels by menstrual cycle phase as measured using 1H-MRS in healthy controls.
  • Time Frame: Each medication will be administered 2 times during a 1-month menstrual cycle.
    Safety Issue?: No

Inclusion Criteria:

• Women ages 18-45 and able to give voluntary written informed consent;
• Regular menstrual periods of 24-35 days in length;
• Body mass index 18.5 to 30 kg/m2;
• No past or present DSM-IV psychiatric or substance dependence diagnosis by structured diagnostic interview (SCID-NP); no substance abuse history within the previous 2 years;
• Absence of mood symptoms across the menstrual cycle during one month of prospective daily ratings with the Daily Record of Severity of Problems (DRSP); the DRSP is based on the DSM-IV research criteria for premenstrual dysphoric disorder (PMDD) and has been used in numerous studies to confirm the presence or absence of significant premenstrual mood and behavioral difficulties;
• Must be willing and able to participate in at least three of the four challenge paradigms.

Exclusion Criteria:

• Medical, neurologic or cerebrovascular disorder (CVA, seizure disorder, etc.);
• Family history of first degree relative with an Axis I psychiatric or substance dependence disorder (excepting alcohol and nicotine) (per subject report);
• Current treatment with psychoactive medication;
• Diabetes controlled by means other than diet;
• Use of steroid contraceptives (any method involving hormones) within the previous 4 months;
• Habitual consumption of more than 7 alcoholic drinks per week or more than 2 drinks on any particular occasion; must be willing to abstain from alcohol consumption for 48 hours prior to each 1H-MRS scan;
• Implanted metallic devices.

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Yale University

Overall Clinical Trial Officials and Contacts

Cynthia N Epperson, MD Principal Investigator Yale School of Medicine  

Information obtained from ClinicalTrials.gov on August 29, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00676026

Study ID Number: 0505027759

ClinicalTrials.gov Identifier: NCT00676026

Health Authority: United States: Institutional Review Board