Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Hot Flashes

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Psychotropic Drugs

Amino Acids

Glycine

Tryptophan

Serotonin

Antidepressive Agents

Phenylalanine

Arginine

Alanine

Leucine

Cysteine

Lysine

Serine

Histidine

Tyrosine

Threonine

Proline

Methionine

Valine

Isoleucine

Half-strength tryptophan depletion drink used as a control

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)

Acute tryptophan depletion

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).

Half-strength tryptophan depletion (Control)

Janet S Carpenter, PhD

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.

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.

The Role of Serotonin in Hot Flashes After Breast Cancer

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

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

Indiana University School of Medicine

Janet Carpenter, PhD, RN

Full Strength Acute Tryptophan Depletion

Half-Strength Tryptophan Depletion - Control

Consented subjects in the entire sample were randomized to one of two groups for the cross-over design study. One group of subjects received a full-strength tryptophan depletion drink during week 1 followed by a half-strength (control) drink week 2. The other group of subjects received a half-strength tryptophan depletion (control) drink during week 1 followed by a full-strength drink week 2.

The final analysis combined groups to compare full strength versus control.

Entire Sample

Age, Categorical

Age, Continuous

Sex: Female, Male

United States

Region of Enrollment

Janet S. Carpenter

The number of subjects with complete serum data for both arms of the study were analyzed.

Serum Tryptophan Levels

Subjects with completed hot flash data during both arms of study.

Objective Subject Hot Flash Frequency

Subjects were randomized to receive both a full-strength acute tryptophan depletion drink and half-strength tryptophan depletion drink (control). Some participants received the full-strength drink first for week 1 and then crossed-over to the half-strength (control) drink for week 2; the other participants received the half-strength (control) drink for week 1 and then crossed over to the full-strength drink for week 2.

Full Strength Acute Tryptophan Depletion and Control

Week 1

Week 2

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
The Role of Serotonin in Hot Flashes After Breast Cancer	NCT00228943	Breast Cancer	Acute tryptopha... Half-strength t...	18 Years -	Indiana University
The Role of Serotonin in Hot Flashes After Breast Cancer	NCT00228943	Breast Cancer	Acute tryptopha... Half-strength t...	18 Years -	Indiana University

Spots Global Cancer Trial Database for acute tryptophan depletion