Cognitive Side Effects of Cancer Therapy, Depression, Recurrent Breast Carcinoma, Stage IA Breast Cancer, Stage IB Breast Cancer, Stage IIA Breast Cancer, Stage IIB Breast Cancer, Stage IIIA Breast Cancer
Conditions
Brief summary
This randomized clinical trial uses an inactive typhoid vaccine to briefly stimulate an immune response in patients with stage I-IIIA breast cancer who received primary cancer treatment and studies whether patients' fitness levels affect how their bodies handle a challenge to their immune system. A vaccine is a substance or group of substances meant to cause the immune system to respond to a tumor or to microorganisms such as bacteria or viruses. Immune responses may cause excess inflammation in the body and behavioral changes, such as depression, fatigue, pain, and problems with thinking and reasoning. Studying immune responses in patients with breast cancer who have undergone primary cancer treatment may help doctors learn whether physical fitness can protect the body from effects of immune system stress and whether it may be able to reduce health problems in patients with breast cancer.
Detailed description
PRIMARY OBJECTIVES: I. To evaluate the relationships between cardiorespiratory fitness and inflammatory and behavioral responses (negative mood, fatigue, pain, and cognitive problems) to typhoid vaccine in breast cancer survivors. II. To determine the effects of age and depressive symptoms on inflammatory and behavioral responses to typhoid vaccine and placebo. III. To assess the ability of cardiorespiratory fitness to moderate age- and depression-related responses to typhoid vaccine. OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients receive inactive typhoid vaccine intramuscularly (IM) at visit 1 followed by placebo IM 30 days later at visit 2. ARM II: Patients receive placebo IM at visit 1 followed by inactive typhoid vaccine IM 30 days later at visit 2. There is an initial screening visit where patients in both arms complete an audio-recorded interview that includes questions about changes in mood and emotion throughout their lives, body measurements, a finger stick to assess for anemia and diabetes markers. During visit 1 and 2, patients in both arms will have blood drawn periodically and complete sets of questionnaires that assess feelings, health behaviors, and personality. Patients also complete cognitive tasks and a temperature sensitivity task at 3-4.5 hours post-injection.
Interventions
BIOLOGICALtyphoid vaccine
Given IM
OTHERPlacebo
Given IM
Sponsors
Ohio State University Comprehensive Cancer Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
35 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Women who have been diagnosed with stage I-IIIA breast cancer will be recruited 1-10 years after the completion of all primary cancer treatment except for longer-term hormonal therapies (tamoxifen, aromatase inhibitors) * All women will be postmenopausal
Exclusion criteria
* A prior history of any other malignancy except basal or squamous cell skin cancers, strokes, diabetes, current heart disease or uncontrolled hypertension, peripheral vascular disease, liver disease, autoimmune and/or inflammatory diseases including rheumatoid arthritis and ulcerative colitis, and other medical conditions that would limit participation in the assessments (e.g., pulmonary disease, orthopedic problems, major psychiatric illness, major cognitive dysfunction, or an acute medical problem) * Anemia * Alcohol or drug abuse * Smoking * Medication exclusions will include steroids as well as statins and other medications with anti-inflammatory actions * Women who have received a typhoid vaccine within the last three years
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC Change in Level of IL-6 | Baseline, 1.5, 3, 5, 6.5, 8 hours post vaccine | AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 1.5, 3, 5, 6.5, 8 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC Change in Pain | baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine | Self-reported intensity of pain on 0-9 scale (0 = no pain; 9 = pain as bad as you can imagine). AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included. |
| AUC Change in Fatigue | baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine | Self-reported intensity of fatigue on 0-9 scales (0 = no fatigue; 9 = fatigue as bad as you can imagine). AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Patients served as her own control between two visits.
typhoid vaccine: Given IM
Placebo: Given IM | 172 |
| Total | 172 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | blood draw problem | 0 | 1 |
| Overall Study | Protocol Violation | 1 | 0 |
| Overall Study | Withdrawal by Subject | 6 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 56.6 years STANDARD_DEVIATION 8.4 |
| BMI 18.5 kg/m^2 to 24.9 kg/m^2 Healthy | 61 Participants |
| BMI <18.5 kg/m^2 Underweight | 0 Participants |
| BMI 25 kg/m^2 to 29.9 kg/m^2 Overweight | 60 Participants |
| BMI >29.9 kg/m^2 Obese | 51 Participants |
| Cancer Stage Stage I | 81 Participants |
| Cancer Stage Stage II | 82 Participants |
| Cancer Stage Stage III | 9 Participants |
| CES-D score | 7.5 units on a scale STANDARD_DEVIATION 6.8 |
| Chemotherapy treatment | 116 Participants |
| Comorbidities | 22 Participants |
| Energy (SF-36 RAND) | 60.4 units on a scale STANDARD_DEVIATION 18.8 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 10 Participants |
| Race (NIH/OMB) More than one race | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 159 Participants |
| Radiation treatment | 105 Participants |
| Sex: Female, Male Female | 172 Participants |
| Sex: Female, Male Male | 0 Participants |
| Trunk Fat | 15.7 kg STANDARD_DEVIATION 6.7 |
| Vo2peak | 22.0 mL/kg/min STANDARD_DEVIATION 5.3 |
| Years since treatment | 3.5 Years STANDARD_DEVIATION 2.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 170 | 0 / 165 |
| other Total, other adverse events | 2 / 170 | 4 / 165 |
| serious Total, serious adverse events | 0 / 170 | 0 / 165 |
Outcome results
Primary
AUC Change in Level of IL-6
AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 1.5, 3, 5, 6.5, 8 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included.
Time frame: Baseline, 1.5, 3, 5, 6.5, 8 hours post vaccine
Population: Each patient had two visits and served as her own control.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC Change in Level of IL-6 | 5.23 ug*hour/ml | Standard Error 0.27 |
| Inactive Typhoid Vaccine | AUC Change in Level of IL-6 | 10.17 ug*hour/ml | Standard Error 0.27 |
Secondary
AUC Change in Fatigue
Self-reported intensity of fatigue on 0-9 scales (0 = no fatigue; 9 = fatigue as bad as you can imagine). AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included.
Time frame: baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine
Population: Each patient had two visits and served as her own control.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC Change in Fatigue | 4.05 units on a scale*hour | Standard Error 0.77 |
| Inactive Typhoid Vaccine | AUC Change in Fatigue | 3.62 units on a scale*hour | Standard Error 0.78 |
Secondary
AUC Change in Pain
Self-reported intensity of pain on 0-9 scale (0 = no pain; 9 = pain as bad as you can imagine). AUC change refers to the 'net incremental' area, which is the area under the curve above the baseline value. Data points used in AUC change calculation include baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine. This can be calculated geometrically by applying the trapezoid rule. When a value falls below the baseline, only the area above the baseline level is included.
Time frame: baseline, 2, 3.5, 5, 6.5, 8.5 hours post vaccine
Population: Each patient had two visits and served as her own control.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo | AUC Change in Pain | 1.06 units on a scale*hour | Standard Error 0.5 |
| Inactive Typhoid Vaccine | AUC Change in Pain | 3.24 units on a scale*hour | Standard Error 0.5 |