Breast CancerNCT00228943
The Role of Serotonin in Hot Flashes After Breast Cancer
A study testing Acute tryptophan depletion in people with Breast Cancer, run by Indiana University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Acute tryptophan depletion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2005to Nov 2008
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Indiana University Cancer Center
Indianapolis, Indiana, 46202
About this study
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.
Read the 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.
- Conditions
- Breast Cancer
- Being tested
- Acute tryptophan depletion, Half-strength tryptophan depletion (Control)
- Keywords
- Breast cancer survivorship, Hot Flashes, Serotonin
- Medical subject headings
- Breast Neoplasms, Hot Flashes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acute tryptophan depletionDietary 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).
| Study group | Role | What they receive |
|---|---|---|
| Acute tryptophan depletion | Experimental | Full-strength tryptophan depletion Receives: Dietary Supplement: Acute tryptophan depletion |
| Control | Active comparator | Half-strength tryptophan depletion drink used as a control Receives: Dietary Supplement: Half-strength tryptophan depletion (Control) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum Tryptophan Levels
Mean serum tryptophan levels (blood draw) at the end of the nadir period.
Measured: baseline, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours
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.
Measured: One 24 hour monitoring session per week for 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2005 (estimated)
- Study startJul 2005
- Primary completionOct 2007
- Study completionNov 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Investigators
- Janet S Carpenter, PhD, Principal investigator, Indiana University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00228943
- Sponsor's protocol ID
- 0501-03
- Other IDs
- DOD-BC043199, 043199
- Status last verified
- Mar 2015
- First submitted
- 14 Sep 2005
- Last updated
- 14 Apr 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Carpenter JS, Yu M, Wu J, Von Ah D, Milata J, Otte JL, Johns S, Schneider B, Storniolo AM, Salomon R, Desta Z, Cao D, Jin Y, Philips S, Skaar TC. Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion. Menopause. 2009 Jul-Aug;16(4):644-52. doi: 10.1097/gme.0b013e318199e9f6.
PubMed 19265726
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Role of Serotonin in Hot Flashes After Breast Cancer
- ClinicalTrials.gov ID
- NCT00228943
- Acronym / sponsor ID
- 0501-03
- Conditions
- Breast Cancer
- Keywords
- Breast cancer survivorship, Hot Flashes, Serotonin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Study start
- Jul 2005
- Primary completion
- Oct 2007 (actual)
- Study completion
- Nov 2008 (actual)
- First posted
- 29 Sep 2005 (estimated)
- Results
- Posted 10 Dec 2008
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acute tryptophan depletion | Experimental | Dietary Supplement: Acute tryptophan depletionFull-strength tryptophan depletion |
| Control | Active comparator | Dietary Supplement: Half-strength tryptophan depletion (Control)Half-strength tryptophan depletion drink used as a control |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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)
Key exclusion criteria (1 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acute tryptophan depletionL-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 supplement | Acute tryptophan depletion |
| 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). | Dietary supplement | Control |
Primary outcome
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.
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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19265726Carpenter JS, Yu M, Wu J, Von Ah D, Milata J, Otte JL, Johns S, Schneider B, Storniolo AM, Salomon R, Desta Z, Cao D, Jin Y, Philips S, Skaar TC. Evaluating the role of serotonin in hot flashes after breast cancer using acute tryptophan depletion. Menopause. 2009 Jul-Aug;16(4):644-52. doi: 10.1097/gme.0b013e318199e9f6.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Janet S Carpenter, PhD principal investigator
Indiana University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acute tryptophan depletion in people with Breast Cancer, run by Indiana University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Dec 2008). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum Tryptophan Levels (time frame: baseline, 1 hour, 2 hours, 3 hours, 4 hours, 5 hours, 6 hours, 7 hours, 8 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00228943, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2015.