Study of PET Scans and Serotonin in Hot Flashes Treatment

Study Overview
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Brief Summary
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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).

Detailed Description
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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.

Official Title
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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

Conditions
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Hot Flashes

Intervention / Treatment
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* Drug: Paroxetine controlled-release
* Drug: Conjugated equine estrogen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Paroxetine<br>Paroxetine controlled-release (2-12.5 mg tablets, orally, every day for 4 weeks) | Drug: Paroxetine controlled-release<br>* 2-12.5 mg tablets, orally, every day for 4 weeks<br>* Other names: Paxil CR;|
| Experimental: Conjugated equine estrogen<br>Conjugated equine estrogen (0.625 mg tablet, orally, every day for 4 weeks) | Drug: Conjugated equine estrogen<br>* 0.625 mg tablet, orally, every day for 4 weeks<br>* Other names: Premarin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | Following 4 weeks of study medication | 
| 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. |  | Following 4 weeks of study medication | 
| 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. |  | Following 4 weeks of study medication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hot flashes, vasomotor symptoms, estrogen, paroxetine