Official Title: “A Feasibility Study of Positron Emission Tomography (PET) of the Serotonin Transporter (SERT) Before and After Treatment With Conjugated Equine Estrogen or Paroxetine for Hot Flashes”

The purpose of this study is to determine in a preliminary manner whether successful therapy of hot flashes can be associated with changes in the serotonin transporter in the brain. The serotonin transporter is important in delivering serotonin into certain portions of the brains (serotonin is a chemical that is important in the control of body temperature, mood, sleep, and other functions).

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Single Group Assignment, Pharmacodynamics Study

Study Primary Completion Date: October 2008

Hot flashes represent the most common complaint among peri- and postmenopausal women. Over 60% of postmenopausal women experience hot flashes, and 10-20% of all postmenopausal women find them nearly intolerable. Despite the prevalence of hot flashes, their pathophysiology is not well understood. Treatment options include non-pharmacological approaches, hormonal interventions, and non-hormonal pharmacological agents. The most effective treatment for hot flashes is estrogen. The most promising non-hormonal treatments for hot flashes are selective serotonin or noradrenergic reuptake inhibitors (SSRI/SNRI). Although estrogen withdrawal is implicated in the initiation of hot flashes, and serotonin's role is well established in thermoregulation, the relationship between estrogen and serotonin is not known. Preclinical studies suggest that both estrogen and SSRI down regulate the serotonin transporter. Clinical studies that further delineate the relationship between effective treatments for hot flashes and the serotonin transporter may shed a new light into the pathophysiology of these symptoms and more importantly, into design of new-targeted treatments.

Intervention(s) in this Clinical Trial

• Drug: Paroxetine controlled-release
  • 2-12.5 mg tablets, orally, every day for 4 weeks
• Drug: Conjugated equine estrogen
  • 0.625 mg tablet, orally, every day for 4 weeks

Primary Measures

• To estimate the proportion of women who have a 50% or greater reduction in frequency of hot flashes following 4 weeks of paroxetine or conjugated equine estrogen.
  • Time Frame: Following 4 weeks of study medication
    Safety Issue?: No
• To evaluate baseline and change in binding of the serotonin transporter in postmenopausal women who suffer hot flashes before and after 4 weeks of paroxetine or conjugated equine estrogen using PET.
  • Time Frame: Following 4 weeks of study medication
    Safety Issue?: No
• To correlate baseline and change in binding of the serotonin transporter using PET with reduction of hot flashes after 4 weeks of conjugated equine estrogen or paroxetine.
  • Time Frame: Following 4 weeks of study medication
    Safety Issue?: No

Inclusion Criteria:

• Postmenopausal women
• 7 or more hot flashes per day for at least 3 months
• Must be able to undergo magnetic resonance (MR) and PET imaging
• Must be able to receive either paroxetine or estrogen

Exclusion Criteria:

• No treatment with hormone therapy or other medications that affect estrogen within the past 3 months
• No evidence of a currently active cancer

Gender Eligibility for this Clinical Trial: Female

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Sidney Kimmel Comprehensive Cancer Center

Overall Clinical Trial Officials and Contacts

Vered Stearns, MD Principal Investigator Johns Hopkins University  

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00249847

Study ID Number: SKCCC J0360

ClinicalTrials.gov Identifier: NCT00249847

Health Authority: United States: Food and Drug Administration