Breast Cancer
Conditions
Keywords
Breast cancer survivorship, Hot Flashes, Serotonin
Brief summary
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.
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.
Interventions
DIETARY_SUPPLEMENTAcute 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)
DIETARY_SUPPLEMENTHalf-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).
Sponsors
Indiana University School of Medicine
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
*
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Tryptophan Levels | 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. |
| Objective Subject Hot Flash Frequency | 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. |
Countries
United States
Participant flow
Recruitment details
Subjects were recruited from a Midwestern outpatient cancer clinic from 2005 to 2007.
Pre-assignment details
260 women were screened, 39 of whom were not interested, 162 were found ineligible.
Participants by arm
| Arm | Count |
|---|---|
| Entire Sample 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. | 28 |
| Total | 28 |
Baseline characteristics
| Characteristic | Entire Sample |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 3 Participants |
| Age, Categorical Between 18 and 65 years | 25 Participants |
| Age, Continuous | 53.4 years STANDARD_DEVIATION 9.6 |
| Region of Enrollment United States | 28 participants |
| Sex: Female, Male Female | 28 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 | 0 / 0 |
Outcome results
Primary
Objective Subject Hot Flash Frequency
Mean of the 24 hour monitoring sessions for each patient based on one 24 hour monitoring session after each intervention using an electronic monitor.
Time frame: One 24 hour monitoring session per week for 8 weeks
Population: Subjects with completed hot flash data during both arms of study.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Strength Acute Tryptophan Depletion | Objective Subject Hot Flash Frequency | 2.30 frequency of hot flashes | Standard Deviation 2.92 |
| Half-Strength Tryptophan Depletion - Control | Objective Subject Hot Flash Frequency | 2.62 frequency of hot flashes | Standard Deviation 3.29 |
Primary
Serum Tryptophan Levels
Mean serum tryptophan levels (blood draw) at the end of the nadir period.
Time frame: baseline, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours
Population: The number of subjects with complete serum data for both arms of the study were analyzed.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Full Strength Acute Tryptophan Depletion | Serum Tryptophan Levels | 0.0034 nmol/ml | Standard Deviation 0.0027 |
| Half-Strength Tryptophan Depletion - Control | Serum Tryptophan Levels | 0.02 nmol/ml | Standard Deviation 0.02 |