Sleep, Circadian Hormonal Dysregulation, and Breast Cancer Survival

October 4, 2017 updated by: David Spiegel, Stanford University

Sleep, Circadian, Hormonal Dysregulation, and Breast Cancer Survival

Recent research provides evidence that disrupted circadian rhythms, including hormonal patterns and sleep, are associated with increased risk of breast cancer incidence and faster progression to mortality. We have observed that a loss of normal diurnal cortisol rhythm associated with more awakenings during the night predicts early mortality with metastatic breast cancer. Other recent studies have shown that nighttime shift work is associated with higher breast cancer incidence, and in a murine model disrupting circadian cortisol cycles produced a doubling of implanted tumor growth. There is also recent evidence that abnormal clock genes are associated with cancer. However, it is not clear whether sleep disruption per se affects breast cancer progression, or whether such an effect is mediated by hormonal and immune dysregulation of this prevalent and hormone-mediated cancer. We propose to study sleep disruption as a prognostic factor in the progression of metastatic breast cancer. We will also examine sleep patterns in association with disrupted circadian rhythms of cortisol, ACTH, and melatonin as well as measures of immune function known to be salient to breast cancer progression. These are natural killer cell cytoxicity and specific cytokine, IL-6. We plan to recruit 105 women 45 years through 75 years with metastatic or recurrent breast cancer and 20 age and SES-matched controls for a two-week at home sleep study with Actiwatch and two nights of in-home EEG monitoring, followed by 28 hours of continuous blood sampling and one night of EEG sleep monitoring in our lab at Stanford. This will provide a full examination of circadian hormones associated with sleep patterns. We will relate these assessments to the subsequent course of breast cancer progression. Results of this study will provide specific evidence regarding how improved sleep management may affect the course of breast cancer. Aim 1: To study 24-hr diurnal rhythms of HPA axis hormones and melatonin in women with metastatic or recurrent breast cancer. Hypothesis 1: Women with metastatic or recurrent breast cancer will have reduced amplitude and disrupted phase of 24-hr diurnal rhythms of cortisol, ACTH, and melatonin. Aim 2: To describe sleep disruption in women with metastatic breast cancer and examine psychosocial, endocrine, and immune factors that may be associated with sleep disruption. Hypothesis 2: Women with metastatic or recurrent breast cancer will have a higher incidence of both at home and laboratory-examined sleep disruption than control women without breast cancer. Hypothesis 3: Poorer sleep quality will be associated with more pain, more emotional suppression in response to stressors, less emotional support, greater depression and anxiety, and greater perceived and traumatic stress. Hypothesis 4: Poorer sleep quality and quantity of sleep and daytime sleepiness and fatigue will be associated with abnormal circadian neuroendocrine (i.e., cortisol, ACTH, and melatonin) and immune patterns (i.e., suppressed day and night time NK activity and loss of NK rhythms; increased day time IL-6 levels and /or loss of IL-6 rhythm). Aim 3: To study the relationship between sleep disruption and survival time among metastatic and recurrent breast cancer patients. Hypothesis 5: Poorer sleep quality and quantity of sleep will predict shorter survival. Hypothesis 6: Reduced diurnal amplitude and an abnormal phase of cortisol will predict shorter survival. Explanatory Aim 4: To investigate whether sleep disruption mediates the relation of psychosocial factors to health outcomes.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
141

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University School of Medicine

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

45 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

Female

Sampling Method

Non-Probability Sample

Study Population

women with breast cancer

Description

Inclusion Criteria:

Inclusion criteria for women with breast cancer:

  1. Female
  2. Between 45 and 75 years old (45<=>75)
  3. Documented metastatic or recurrent breast cancer
  4. Karnofsky rating of at least 70% (measure of physical ability used to assess medically ill patients)
  5. Residence within the Greater San Francisco Bay Area
  6. Proficiency in English sufficient to complete questionnaires
  7. Postmenopausal
  8. Non smoker (occasional smoking will be ok, they need to agree to stop smoking during study participation. If smoking cessation will cause withdrawal, they can not participate)
  9. Willing to go through a 30 day washout period if they are currently on Decadron or any other corticosteroids (depending on the dose, may be able to reduce 30 days to 2 weeks)
  10. If taking Benzodiazepines, willing to stop 3 days before the collection of physiological measures, such as the 2 week at home sleep recordings and then the 3 days before and during the GCRC (if not possible, washout period may be reduced to 3 days before and during the CTRU/GCRC stay)
  11. Willingness to discontinue taking melatonin one week before the CTRU/GCRC stay
  12. Willingness to discontinue any current sleeping medications 3 days before 2 week at home sleep data collection through the end of study participation (if not possible, washout period may be reduced to 3 days before and during the CTRU/GCRC stay)
  13. Willingness to abstain from traveling 2 or more time zones away from California (Pacific time), two weeks before and during participation in the study
  14. Willing/able to refrain from doing shift-work in a non-traditional schedule (such as 4pm to midnight or 10pm to 6am) starting two weeks before at home sleep collection through the end of study participation.
  15. Agree to catheterization for blood sample collection
  16. Agrees with the use of heparin during the blood draws (used to keep IV line from clotting)
  17. Has graduated high school or obtained GED
  18. US Citizen or resident viable for payment, legally

Inclusion criteria for healthy controls:

  1. Female
  2. Between 45 and 75 years old (45<=>75)
  3. No history of any type of cancer
  4. Residence within the Greater San Francisco Bay Area
  5. Proficiency in English to complete questionnaires
  6. Post Menopausal
  7. Non-smoker (occasional smoking will be ok, they need to agree to stop smoking during study participation. If smoking cessation will cause withdrawal, they can not participate)
  8. If taking benzodiazepines, willing to stop 3 days before the collection of physiological measures, such as the 2 week at home sleep recordings and then the 3 days before and during the GCRC (if not possible, washout period may be reduced to 3 days before and during the CTRU/GCRC stay)
  9. Willingness to discontinue taking melatonin one week before the CTRU/GCRC stay
  10. Willingness to discontinue any current sleeping medications 3 days before 2 week at home sleep data collection through the end of study participation (if not possible, washout period may be reduced to 3 days before and during the CTRU/GCRC stay)
  11. Willingness to abstain from traveling 2 or more time zones away from California (Pacific time), two weeks before and during participation in the study
  12. Willing/able to refrain from doing shift-work in a non-traditional schedule (such as 4pm to midnight or 10pm to 6am) starting two weeks before at home sleep collection through the end of study participation
  13. Agree to catheterization for blood sample collection
  14. Agrees with the use of heparin during the blood draws (used to keep IV line from clotting)
  15. Has graduated high school or obtained GED
  16. US Citizen or resident viable for payment, legally
  17. Pittsburgh Sleep Quality Index (PSQI) score >6

Exclusion Criteria:Exclusion criteria for women with breast cancer:

  1. Other active cancers within the past 10 years other than breast cancer, basal cell or squamous cell carcinomas of the skin, or in situ cancer of the cervix
  2. Concurrent medical condition likely to influence short term survival (such as liver disease, asthma etc, depending on severity)
  3. History of major psychiatric illness that required hospitalization or medication
  4. Substance Dependence or abuse
  5. Low hematocrit (up to the digression of the PI, may be able to participate in parts of the protocol)
  6. Bilateral lymph nodes removed
  7. Diagnosis of diabetes (need to check with PI, some mild cases of diabetes may be ok)
  8. Positive supraclavicular lymph nodes as the only metastatic lesion at the time of initial diagnosis
  9. PICC line too close to the few available veins, viable for catheterization (too high of a risk for infection/complication), and is on the only arm which did not have lymph node surgery

Exclusion criteria for healthy controls:

  1. Concurrent medical condition likely to influence short term survival (such as liver disease, asthma etc, depending on severity)
  2. History of major psychiatric illness that required hospitalization or medication
  3. Substance dependence or abuse
  4. Low hematocrit (up to the digression of the PI, may be able to participate in parts of the protocol)
  5. Diagnosis of diabetes (need to check with PI, some mild cases of diabetes may be ok)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 1, 2006

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
August 31, 2011

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
August 31, 2011

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 20, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 20, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 22, 2007

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
October 6, 2017

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 4, 2017

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
October 1, 2017

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • BRSADJ0013 (Other Identifier: Stanford University)
  • 97312 (Other Identifier: Stanford University Alternate IRB Approval Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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