Clinical trial NCT01177124: Mindfulness-Based Stress Reduction (MBSR) Symptom Cluster Trial for Breast Cancer Survivors
Official title: Mindfulness-Based Stress Reduction (MBSR) Symptom Cluster Trial for Breast Cancer Survivors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Breast Cancer
Keywords: Breast cancer
Survivors
Mindfulness-Based Stress Reduction (MBSR)
Symptoms
Immune markers
Lead sponsor: University of South Florida
Sponsor class: OTHER
First posted: 2010-08-06
Enrollment: 300
Sex: FEMALE
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: The purpose of this study among breast cancer survivors is three-fold: (i) to evaluate the efficacy of the MBSR(BC) program in improving psychological and physical symptoms, quality of life and measures of immune function and a stress hormone (cortisol); (ii) to test whether positive effects achieved from the MBSR(BC) program are mediated through changes in mindfulness and fear of recurrence of breast cancer; and (iii) to evaluate whether positive effects achieved from the MBSR(BC) program are modified by specific patient characteristics measured at baseline.

Detailed description: Breast cancer survivors are living longer and may be living with many symptoms incurred from the disease and its treatment. Survivors from 1 to 2 years off treatment report continued fatigue, depression, pain and sleep disturbances (Kenefick 2006; Byar et al. 2006). Patients often present with several concurrent symptoms (Dodd et al. 2001; Esper and Heidrich 2005). It is believed that symptoms tend to cluster together (two or more concurrent symptoms related to one another and independent of other symptoms) and may have natural associations, similar shared pathways and underlying mechanisms (Barsevick 2007). Currently, little is known about how symptoms cluster in breast cancer survivors after treatment, underlying mechanisms, and if interventions can influence multiple symptoms simultaneously (Lee et al. 2004; Cleeland et al. 2003). Very few studies have tested interventions during post-treatment survivorship (Cimprich et al. 2005; Mishel et al. 2005; Stanton et al. 2005; Scheier et al. 2005). Mindfulness-Based Stress Reduction (MBSR), a standardized form of meditation and yoga, has been shown to be effective in reducing anxiety, depression and stress in patients with chronic pain (Kabat-Zinn et al. 1992; Miller et al. 1995; Teasdale et al. 2000; Kabat-Zinn et al. 1985). Preliminary results from 2 pilot studies conducted by our research team provide support that MBSR for breast cancer survivors may be effective in markedly reducing symptoms, increasing quality of life, and decreasing fears of recurrence (Lengacher et al. 2009; Lengacher et al. 2006). This proposed study builds on our preliminary data of the MBSR Breast Cancer Program (BC) to reduce stress, biological markers of the stress response (pro-inflammatory cytokines) and improve physical, and psychological symptoms and quality of life in breast cancer survivors.

We aim to determine: (i) the extent to which the MBSR(BC) program is efficacious in improving outcomes; (ii) whether positive effects from MBSR(BC) are mediated through increased mindfulness and reduced fear of recurrence; and (iii) if a subgroup of patients can be determined to derive the most benefit from MBSR(BC). Formal specific aims are as follows:

Aim (1). Evaluate the efficacy of the MBSR(BC) program in improving psychological and physical symptoms, quality of life and measures of immune function and a stress hormone (cortisol). We hypothesize that compared to the usual care regimen, patients randomly assigned to the MBSR(BC) program will experience greater improvements at 6 weeks and sustained improvements at 12 weeks in the following:

1. Individual psychological symptoms, including depression anxiety, and perceived stress;
2. Individual physical symptoms, including pain, fatigue and sleep dysfunction;
3. Quality of life;
4. Biological stress markers (pro-inflammatory immune cytokines, cellular adhesion molecules, lymphocyte subsets) and a stress-related hormone (cortisol).

Aim (2). Test whether positive effects achieved from the MBSR(BC) program (defined in 1a-1d) are mediated through changes in mindfulness and fear of recurrence of breast cancer. We hypothesize that:

1. Patients in the MBSR(BC) program will report greater increases in mindfulness and larger reductions in fear of recurrence compared to patients assigned to the usual care regimen.
2. Increased mindfulness will relate directly to improvements in psychological and physical symptoms, quality of life and measures of immune function and a stress hormone (cortisol).
3. Reductions in fear of recurrence will be associated with improvements in psychological and physical symptoms, quality of life and measures of immune function and a stress hormone (cortisol).
4. A primary pathway through which MBSR exerts its positive effects (defined in 1a-1d) will be through increased mindfulness leading to reduced fear of recurrence of cancer.

Aim (3). Evaluate whether positive effects achieved from the MBSR(BC) program (defined in 1a-1d) are modified by specific patient characteristics measured at baseline. We hypothesize that efficacy of the MBSR(BC) program will be greatest among patients with:

1. High anxiety, high perceived stress, low optimism and poor quality of life
2. Specific symptom profiles (i.e. highly distressed patients), as determined by grouping (clustering) patients according to their presenting symptoms.

To achieve this research goal, we have proposed a 2-group randomized clinical trial among 300 breast cancer survivors who have undergone lumpectomy and/or mastectomy and radiation and/or chemotherapy in the past two years. The MBSR(BC) program will be evaluated against a waitlisted usual care regimen (UC), with patient assessments made at baseline, 6 weeks, and 12 weeks. Patient assessments will provide data on depression, state anxiety, perceived stress, fatigue, pain, sleep, symptom severity, quality of life, mindfulness, fear of recurrence, optimism and social support. Additionally, blood and saliva samples will be collected from participants. Biological stress markers will be measured by blood specimen collection; biological stress markers will include pro-inflammatory and anti-inflammatory cytokines (IL-1β, TNF-α, IL-6, IL-10, IL-1-RA, TNF-RA, IL-8, IFN-gamma), cellular adhesion markers (CD11a, CD54, CD62L, CD45RA, CD45RO) and lymphocyte subsets (CD3, CD19, CD16+56). A stress hormone, cortisol, will be measured by saliva specimen collection. The MBSR(BC) intervention is an adapted 6-week program that follows the curriculum of an 8-week program established by Kabat Zinn and Santorelli. Prior to formal hypothesis testing, the distributions of all explanatory and outcome variables, as well as covariates, will be examined. For outcome variables with skewed distributions, appropriate transformations (e.g. square root, logarithmic, etc.) will be performed to satisfy normality requirements for parametric multivariable linear modeling. This will include choosing the transformation which yields the lowest Anderson-Darling score. In instances in which appropriate transformations cannot be achieved, non-parametric methods will be used.

Results from this study will advance conceptual and clinical knowledge of how a stress-reducing intervention impacts symptoms among breast cancer survivors and in whom it may be most efficacious. Determining stress-related biological effects may be applicable to other stress-reducing intervention studies. This symptom and symptom cluster assessment and intervention model will further our understanding of biology and behavior and test a predictive and personalized model of health care.

Eligibility criteria: Inclusion Criteria:

* 21 years or older
* Diagnosed with Stage 0, I, II, or III breast cancer
* Undergone lumpectomy and/or mastectomy and are at 2 weeks from end of treatment with adjuvant radiation and/or chemotherapy or are a maximum of 2 years out from completion of such treatment
* Ability to read and speak English at the 8th grade level or above to respond to survey questions

Exclusion Criteria:

* Advanced stage (IV) cancer
* Current psychiatric diagnosis
* Recurrent treatment for prior breast cancer

Primary outcomes:
measure: To evaluate the efficacy of the MBSR(BC) program in improving psychological and physical symptoms, quality of life and measures of immune function and a stress hormone (cortisol)
timeFrame: Baseline, 6 weeks and 12 weeks
Secondary outcomes:
measure: To test whether positive effects achieved from the MBSR(BC) program are mediated through changes in mindfulness and fear of recurrence of breast cancer
timeFrame: Baseline, 6 weeks and 12 weeks
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Carol and Frank Morsani Center for Advanced Healthcare
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center and Research Institute
state: Florida
city: Tampa
country: United States
facility: University of South Florida
state: Florida
Study officials:
affiliation: University of South Florida
name: Cecile A Lengacher, RN, PhD
role: PRINCIPAL_INVESTIGATOR
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