The Role of Serotonin in Hot Flashes After Breast Cancer

This study has been completed.
Sponsor:
Information provided by:
Indiana University
ClinicalTrials.gov Identifier:
NCT00228943
First received: September 14, 2005
Last updated: April 29, 2009
Last verified: April 2009
  Purpose

The purpose of this proposal is to improve our understanding of the role of tryptophan and serotonin in hot flashes. The main hypothesis is that alterations in tryptophan and serotonin levels are involved in the induction of hot flashes in women with breast cancer and genetic variations in the serotonin receptors and transporters also play a role.


Condition Intervention
Breast Cancer
Dietary Supplement: Acute tryptophan depletion
Dietary Supplement: Half-strength tryptophan depletion (Control)

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: The Role of Serotonin in Hot Flashes After Breast Cancer

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Serum Tryptophan Levels [ Time Frame: baseline, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours ] [ Designated as safety issue: No ]
  • Objective Subject Hot Flash Frequency [ Time Frame: One 24 hour monitoring session per week for 8 weeks ] [ Designated as safety issue: No ]

Enrollment: 28
Study Start Date: July 2005
Study Completion Date: November 2008
Primary Completion Date: October 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Acute tryptophan depletion
Full-strength tryptophan depletion
Dietary Supplement: Acute tryptophan depletion
L-alanine (5.5g), L-arginine (4.9g), L-cysteine (2.7g), glycine (3.2g), L-histidine (3.2g), L-isoleucine (8.0g), L-leucine (13.5g), L-lysine (11.0g), L-methionine (3.0g), L-phenylalanine (5.7g), L-proline (12.2g), L-serine (6.9g), L-threonine (6.9g), L-tyrosine (6.9g), L-valine (8.9g)
Active Comparator: Control
Half-strength tryptophan depletion drink used as a control
Dietary Supplement: Half-strength tryptophan depletion (Control)
L-alanine (1.4g), L-arginine (1.2g), L-cysteine (0.7g), glycine (0.8g), L-histidine (0.8g), L-isoleucine (2.0g), L-leucine (3.4g), L-lysine (2.8g), L-methionine (0.8g), L-phenylalanine (1.4g), L-proline (3.1g), L-serine (1.7g), L-threonine (1.7g), L-tyrosine (1.7g), L-valine (2.2g), and fillers (7.95g).

Detailed Description:

Among women with breast cancer, hot flashes are a frequent, severe and bothersome symptom. For this group, hot flashes are negatively related to mood, affect, and daily activities and can compromise compliance with life-saving medications (e.g., tamoxifen). Over 60% of breast cancer survivors report hot flashes, with 59% stating they are extremely severe and 44% reporting them to be extremely bothersome. Unfortunately, limitations in our understanding of hot flash physiology limit clinicians' abilities to fully treat this symptom. Although the current non-hormonal treatment of choice for hot flashes after breast cancer targets the central serotonin system (e.g., paroxetine, venlafaxine), the role of serotonin in hot flashes has not been directly tested. Because the effectiveness of these agents has been based largely on improvement in subjective reporting of hot flashes, it is not clear whether benefits are due to physiological effects on hot flashes or due to improvements in mood or other related symptoms. In addition, these and other currently available treatments are not acceptable, appropriate, or effective for all women with breast cancer. Understanding the physiological mechanisms involved in hot flashes after breast cancer will enable us to develop more targeted behavioral and/or pharmacological therapies to be used in lieu of, or in addition to, currently available therapies so that we can eradicate hot flashes and improve the quality of life for women with breast cancer.

Results implicating direct effects of tryptophan and serotonin on objective hot flashes will help guide the development of improved interventions for alleviating hot flashes in women with breast cancer. These interventions may target the central serotonin system either behaviorally (e.g., diet) or pharmacologically (e.g., alternative drug therapeutics). If direct manipulation of tryptophan and serotonin does not affect hot flashes, these findings will be equally as useful in guiding future research on non-serotonin related etiologies and interventions. Findings from this study will ultimately be used to eradicate hot flashes as a frequent, severe and bothersome breast cancer treatment related condition, thereby, improving quality of life for all women with breast cancer.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • At least 18 years of age
  • Willing and able to provide informed consent
  • Reporting daily hot flashes
  • Able to read, write, and speak English
  • Postmenopausal to limit sample variability (> 12 months amenorrhea)
  • Greater then 1 month but < 5 years post-treatment (surgery, radiation, chemotherapy) for non-metastatic breast cancer.
  • These criteria allow inclusion of women successfully treated for recurrent breast cancer since there is no known reason to exclude them. Menopausal status is assessed using self-reports due to problems in reliably measuring follicle-stimulating hormone levels and estradiol in tamoxifen users.

Exclusion Criteria:

  • Exclusion criteria are current depression, history of migraines or hepatitis, abnormal chemistry profile (e.g., sodium, potassium, glucose), or a positive urine drug screen for illegal substances.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00228943

Locations
United States, Indiana
Indiana University Cancer Center
Indianapolis, Indiana, United States, 46202
Sponsors and Collaborators
Indiana University School of Medicine
Investigators
Principal Investigator: Janet S Carpenter, PhD Indiana University School of Medicine
  More Information

Publications:
Responsible Party: Janet Carpenter, PhD, RN, Indiana University School of Nursing
ClinicalTrials.gov Identifier: NCT00228943     History of Changes
Other Study ID Numbers: 0501-03, DOD-BC043199, 043199
Study First Received: September 14, 2005
Results First Received: November 13, 2008
Last Updated: April 29, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Breast cancer survivorship
Hot Flashes
Serotonin

Additional relevant MeSH terms:
Breast Neoplasms
Hot Flashes
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Signs and Symptoms
Serotonin
Tryptophan
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 15, 2014