Study of PET Scans and Serotonin in Hot Flashes Treatment

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 Overview

• Status: Terminated
• Conditions: Hot Flashes
• Intervention / Treatment: Drug: Paroxetine controlled-release; Drug: Conjugated equine estrogen

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21231
      • Johns Hopkins University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
• Investigators: Principal Investigator: Vered Stearns, MD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start: October 1, 2005
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): April 1, 2008

Study Registration Dates

• First Submitted: November 4, 2005
• First Submitted That Met QC Criteria: November 4, 2005
• First Posted (Estimate): November 7, 2005

Study Record Updates

• Last Update Posted (Estimate): October 2, 2014
• Last Update Submitted That Met QC Criteria: October 1, 2014
• Last Verified: October 1, 2014

More Information

Terms related to this study

• Keywords: Hot flashes, vasomotor symptoms, estrogen, paroxetine
• Additional Relevant MeSH Terms: Hot Flashes; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Serotonin Uptake Inhibitors; Neurotransmitter Uptake Inhibitors; Membrane Transport Modulators; Serotonin Agents; Antidepressive Agents; Cytochrome P-450 Enzyme Inhibitors; Antidepressive Agents, Second-Generation; Cytochrome P-450 CYP2D6 Inhibitors; Paroxetine; Estrogens; Estrogens, Conjugated (USP)
• Other Study ID Numbers: SKCCC J0360