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Completed

NCT Number: NCT00228943

The Role of Serotonin in Hot Flashes After Breast Cancer

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.

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Key information

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Indiana University Cancer Center

Indianapolis, Indiana, 46202, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Acute tryptophan depletion

Dietary Supplement

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)

Half-strength tryptophan depletion (Control)

Dietary Supplement

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).

Primary outcomes

  1. Serum Tryptophan Levels

    Time frame: baseline, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours

    Mean serum tryptophan levels (blood draw) at the end of the nadir period.

  2. Objective Subject Hot Flash Frequency

    Time frame: One 24 hour monitoring session per week for 8 weeks

    Mean of the 24 hour monitoring sessions for each patient based on one 24 hour monitoring session after each intervention using an electronic monitor.

Sponsors and collaborators

Lead sponsor

Indiana University

Other

Registry information

Important dates

Study start
2005
Primary completion
2007
Study completion
2008
First posted
Sep 29, 2005
Registry last updated
Apr 14, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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