Bone and Bones, Breast Neoplasms
Conditions
Brief summary
Both the calcitriol and exercise interventions are aimed at reducing fracture risk by maintaining proper bone density, thereby preventing osteoporotic/osteopenic conditions and increasing muscle mass. Both calcitriol and exercise are efficacious in maintaining proper bone health and muscle mass among the general population, but little research has been done on breast cancer patients and survivors. The combination of calcitriol and exercise, which function through different but similar mechanisms, could produce interactive effects in reducing fracture risk among breast cancer survivors. Hypothesis: A combination of calcitriol along with a structured home-based walking and progressive resistance exercise program will be efficacious in preventing bone resorption and in increasing bone formation among survivors of invasive breast cancer.
Detailed description
Primary Objective To collect data on the efficacy and feasibility of a supplementation of calcitriol with/without an accompanying structured home-based walking/progressive resistance exercise program for improving bone health among breast cancer survivors. Secondary Objectives To collect data on the efficacy and feasibility of a supplementation of calcitriol with/without an accompanying structured home-based walking/progressive resistance exercise program for increasing strength among breast cancer survivors. To collect data on the efficacy and feasibility of a supplementation of calcitriol with/without an accompanying structured home-based walking/progressive resistance exercise program for improving skeletal muscle mass among breast cancer survivors.
Interventions
DRUGCalcitriol
Calcitriol tablet taken once per week.
BEHAVIORALExercise
Exercise consisting of progressive walking and resistance band training
DIETARY_SUPPLEMENTMultivitamin
Sponsors
University of Rochester
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Must be female. * Women of child-bearing potential (i.e. women who are pre-menopausal or not surgically sterile) must use acceptable contraceptive methods (abstinence, intrauterine device (IUD), or double barrier device) and must have a negative serum or urine pregnancy test within 1 week prior to beginning treatment on this trial. Contraceptive use needs to be continued at least 1 month after the trial has ended. * Must provide informed consent. * Must be willing to discontinue use of calcium and/or vitamin D supplements. * Participants must have an ionized serum calcium level within normal limits (1.19-1.29mmol/L) and a total corrected serum calcium of \< 10.2mg/dl. * Must have a functional capacity rating of ≤ 2 on the Eastern Cooperative Oncology Group (ECOG) performance status when assessed at baseline. * Must have the approval of their treating physician (or physician's nurse practitioner or physician's assistant) to participate in sub-maximal physiological fitness testing and a low to moderate home-based walking and progressive resistance exercise program and to receive the 12-week supplementation of calcitriol 45 μg. Participants assigned to either of the calcitriol treatment arms will be instructed to stop taking calcium and/or vitamin D supplements. * Must be less than five years from the diagnosis of breast cancer and have received chemotherapy, radiation therapy, and/or hormonal therapy. Chemotherapy and radiation therapy, if received, must have been completed prior to study enrollment. Hormonal therapy may be ongoing.
Exclusion criteria
* Subjects with life-threatening conditions that would preclude them from breast cancer treatment including chronic cardiac failure, which is unstable despite medication use, uncontrolled hypertension, uncontrolled diabetes mellitus, or unstable coronary artery disease. * Patients who had a myocardial infarction within the past year. * Patients with severe metabolic disorders, which includes phenylketonuria (PKU), homocystinuria, and Fabry's disease, that would preclude them from taking calcitriol. * Patients with impaired renal function (CRCL \< 60 mL/min) or who had kidney stones (calcium salt) within the past 5 years. * Patients with hypercalcemia (corrected serum Ca \> 10.2 mg/dl) or a history of hypercalcemia or vitamin D toxicity. * Patients currently taking calcium supplements or aluminum-based antacids must be willing to discontinue their use if they are to enroll in the study. * Patients currently taking vitamin D supplements must immediately discontinue their use if they are to enroll in the study. * Patients with a known sensitivity to calcitriol. * Women who are pregnant or lactating. * Previously verified diagnosed of osteoporosis. * Women on antiresorptive drugs (e.g. bisphosphonates) within the past year. * Patients not capable of participating in an exercise intervention due to severe knee arthrosis or ligament/cartilage injuries of the lower extremities. * Women currently using oral contraception. * Women with malabsorptive syndromes (i.e. cystic fibrosis, chronic pancreatitis) or taking medications that decrease the absorption of fat soluble vitamins (i.e. Orlistat, Questran). * Participants assigned to calcitriol who are routinely taking a multivitamin supplement may continue the supplement as long as the amount of vitamin D in the supplement is not in excess of the RDA (recommended daily allowance) of 400 IU or 10 μg. If they are not taking a multivitamin supplement, they will be asked to not start supplementation while on study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Bone Formation (Calcitriol) | Week 12 | Bone Formation using Serum BSAP (Calcitriol comparison) The Bone-Specific Alkaline Phosphatase (BSAP) assay provides a general index of bone formation and a specific index of total osteoblast activity. BSAP and osteocalcin are the most effective markers of bone formation and are particularly useful for monitoring bone formation therapies and antiresorptive therapies. |
| Bone Resorption (Exercise) | Week 12 | Bone Resorption using Serum NTx (Exercise comparison) Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Elevated levels of serum NTx indicate elevated bone resorption. Elevated bone resorption is the primary cause of agerelated bone loss and that low bone mass often results in osteopenia and is the major cause of osteoporosis. The measurement range is in nanoMoles (NM) Bone Collagen Equivalents (BCE). |
| Bone Resorption (Calcitriol) | Week 12 | Bone Resorption using Serum NTx (Calcitriol comparison) Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Elevated levels of serum NTx indicate elevated bone resorption. Elevated bone resorption is the primary cause of agerelated bone loss and that low bone mass often results in osteopenia and is the major cause of osteoporosis. The measurement range is in nanoMoles (nm) Bone Collagen Equivalents (BCE). |
| Bone Formation (Exercise) | Week 12 | Bone Formation using Serum BSAP (Exercise comparison) The Bone-Specific Alkaline Phosphatase (BSAP) assay provides a general index of bone formation and a specific index of total osteoblast activity. BSAP and osteocalcin are the most effective markers of bone formation and are particularly useful for monitoring bone formation therapies and antiresorptive therapies. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Handgrip (kg) Strength - (Exercise) | Week 12 | Handgrip (kg) Strength (Exercise comparison) Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. It is typically measured in kilograms or pounds and varies by sex and age. Normative data for females is AGE 35-39 --\> 20.3-34.1kg; AGE 40-44 --\> 18.9-32.7kg; AGE 45-49 --\> 18.6-32.4kg; AGE 50-54 --\> 18.1-31.9kg; AGE 55-59 --\> 17.7-31.5kg; AGE 60-64 --\> 17.2-31.0kg; AGE 65-69 --\> 15.4-27.2kg; AGE 70-99 --\> 14.7-24.5kg. Values less than the normal range are considered weak strength. Values greater than the normal range are considered strong strength. |
| Handgrip (kg) Strength - (Calcitriol) | Week 12 | Handgrip (kg) Strength - (Calcitriol comparison) Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. It is typically measured in kilograms or pounds and varies by sex and age. Normative data for females is AGE 35-39 --\> 20.3-34.1kg; AGE 40-44 --\> 18.9-32.7kg; AGE 45-49 --\> 18.6-32.4kg; AGE 50-54 --\> 18.1-31.9kg; AGE 55-59 --\> 17.7-31.5kg; AGE 60-64 --\> 17.2-31.0kg; AGE 65-69 --\> 15.4-27.2kg; AGE 70-99 --\> 14.7-24.5kg. Values less than the normal range are considered weak strength. Values greater than the normal range are considered strong strength. |
| Body Mass Index (Exercise) | Week 12 | Body Mass Index (BMI) - (Exercise Comparison) Measure Description: Body Mass Index (BMI) is a person's weight in kilograms divided by the square of height in meters. Values below 18.5 represent Underweight, 18.5 to 24.9 represent Normal or Healthy Weight, 25.0 to 29.9 represent Overweight and 30.0 and above represent Obese. |
| Body Mass Index (Calcitriol) | Week 12 | Body Mass Index(BMI) - (Calcitriol comparison) Measure Description: Body Mass Index (BMI) is a person's weight in kilograms divided by the square of height in meters. Values below 18.5 represent Underweight, 18.5 to 24.9 represent Normal or Healthy Weight, 25.0 to 29.9 represent Overweight and 30.0 and above represent Obese. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Multivitamin Multivitamin used as control group.
Multivitamin | 10 |
| Exericse Exercise consisting of progressive walking and resistance band training.
Exercise: Exercise consisting of progressive walking and resistance band training | 10 |
| Calcitriol Calcitriol pill taken once per week.
Calcitriol: Calcitriol tablet taken once per week. | 10 |
| Calcitriol and Exercise Calcitriol pill taken once per week plus Exercise consisting of progressive walking and resistance band training.
Calcitriol: Calcitriol tablet taken once per week.
Exercise: Exercise consisting of progressive walking and resistance band training | 11 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Physician Decision | 0 | 0 | 1 | 0 |
| Overall Study | Unable to obtain final blood draw | 0 | 0 | 0 | 2 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 0 | 0 |
Baseline characteristics
| Characteristic | Exericse | Calcitriol | Multivitamin | Calcitriol and Exercise | Total |
|---|---|---|---|---|---|
| Age, Continuous | 55.8 years STANDARD_DEVIATION 6.7 | 52.0 years STANDARD_DEVIATION 6.8 | 50.9 years STANDARD_DEVIATION 8.2 | 55.1 years STANDARD_DEVIATION 8.7 | 53.5 years STANDARD_DEVIATION 7.8 |
| Body Mass Index (BMI) | 32.4 kg/m^2 STANDARD_DEVIATION 7.5 | 28.4 kg/m^2 STANDARD_DEVIATION 5.5 | 31.3 kg/m^2 STANDARD_DEVIATION 6 | 28.1 kg/m^2 STANDARD_DEVIATION 3.6 | 29.9 kg/m^2 STANDARD_DEVIATION 5.9 |
| Current Cardiovascular Exercise No | 4 Participants | 4 Participants | 5 Participants | 4 Participants | 17 Participants |
| Current Cardiovascular Exercise Yes | 6 Participants | 6 Participants | 5 Participants | 7 Participants | 24 Participants |
| Current Resistance Training No | 10 Participants | 8 Participants | 8 Participants | 8 Participants | 34 Participants |
| Current Resistance Training Yes | 0 Participants | 2 Participants | 2 Participants | 3 Participants | 7 Participants |
| Hormonal Therapy Aromatase Inhibitor | 5 Participants | 4 Participants | 3 Participants | 7 Participants | 19 Participants |
| Hormonal Therapy Tamoxifen | 4 Participants | 6 Participants | 7 Participants | 4 Participants | 21 Participants |
| Marital Status Married | 7 Participants | 9 Participants | 6 Participants | 11 Participants | 33 Participants |
| Marital Status Single/Divorced/Widowed | 3 Participants | 1 Participants | 4 Participants | 0 Participants | 8 Participants |
| Menopausal Status Postmenopausal | 9 Participants | 5 Participants | 4 Participants | 8 Participants | 26 Participants |
| Menopausal Status Premenopausal | 1 Participants | 5 Participants | 6 Participants | 3 Participants | 15 Participants |
| Prior Chemotherapy No | 3 Participants | 3 Participants | 3 Participants | 5 Participants | 14 Participants |
| Prior Chemotherapy Yes | 7 Participants | 7 Participants | 7 Participants | 6 Participants | 27 Participants |
| Prior Radiotherapy No | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Prior Radiotherapy Yes | 10 Participants | 10 Participants | 10 Participants | 11 Participants | 41 Participants |
| Race/Ethnicity, Customized Not White | 0 Participants | 2 Participants | 1 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 10 Participants | 8 Participants | 9 Participants | 11 Participants | 38 Participants |
| Serum BMOI - Bone Metabolism Index | 0.34 Z-Score STANDARD_DEVIATION 1.05 | -0.12 Z-Score STANDARD_DEVIATION 1.44 | 0.03 Z-Score STANDARD_DEVIATION 1.25 | -0.26 Z-Score STANDARD_DEVIATION 0.96 | 0.01 Z-Score STANDARD_DEVIATION 1.17 |
| Serum BSAP - Bone Formation | 13.8 ng/ml STANDARD_DEVIATION 7.2 | 12.2 ng/ml STANDARD_DEVIATION 7.4 | 12.2 ng/ml STANDARD_DEVIATION 7.1 | 12.0 ng/ml STANDARD_DEVIATION 5.6 | 12.6 ng/ml STANDARD_DEVIATION 6.7 |
| Serum NTx - Bone Resorption | 11.6 nm BCE STANDARD_DEVIATION 5.7 | 13.4 nm BCE STANDARD_DEVIATION 8.1 | 12.2 nm BCE STANDARD_DEVIATION 10 | 14.4 nm BCE STANDARD_DEVIATION 9.5 | 12.9 nm BCE STANDARD_DEVIATION 8.2 |
| Sex: Female, Male Female | 10 Participants | 10 Participants | 10 Participants | 11 Participants | 41 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Stage of Cancer 0 / I | 2 Participants | 5 Participants | 3 Participants | 7 Participants | 17 Participants |
| Stage of Cancer II | 6 Participants | 4 Participants | 4 Participants | 3 Participants | 17 Participants |
| Stage of Cancer III | 2 Participants | 1 Participants | 3 Participants | 1 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 11 |
| other Total, other adverse events | 6 / 10 | 6 / 10 | 5 / 10 | 5 / 11 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 | 0 / 10 | 0 / 11 |
Outcome results
Primary
Bone Formation (Calcitriol)
Bone Formation using Serum BSAP (Calcitriol comparison) The Bone-Specific Alkaline Phosphatase (BSAP) assay provides a general index of bone formation and a specific index of total osteoblast activity. BSAP and osteocalcin are the most effective markers of bone formation and are particularly useful for monitoring bone formation therapies and antiresorptive therapies.
Time frame: Week 12
Population: No Calcitriol group consists of Multivitamin arm and Exercise arm N=20; Calcitriol group consists of Calcitriol and Calcitriol+Exercise arms N=20\*\*~\*\* 1 subject has missing data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Bone Formation (Calcitriol) | 12.0 ng/ml | Standard Error 1.268 |
| Exercise | Bone Formation (Calcitriol) | 16.3 ng/ml | Standard Error 0.802 |
p-value: <0.01ANCOVA
Primary
Bone Formation (Exercise)
Bone Formation using Serum BSAP (Exercise comparison) The Bone-Specific Alkaline Phosphatase (BSAP) assay provides a general index of bone formation and a specific index of total osteoblast activity. BSAP and osteocalcin are the most effective markers of bone formation and are particularly useful for monitoring bone formation therapies and antiresorptive therapies.
Time frame: Week 12
Population: No Exercise group consists of Multivitamin and Calcitriol arms N=20; Exercise group consists of Exercise and Calcitriol+Exercise arms N=20\*\*~\*\*1 subject has missing data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Bone Formation (Exercise) | 13.8 ng/ml | Standard Error 1.513 |
| Exercise | Bone Formation (Exercise) | 14.7 ng/ml | Standard Error 0.957 |
p-value: 0.49ANCOVA
Primary
Bone Resorption (Calcitriol)
Bone Resorption using Serum NTx (Calcitriol comparison) Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Elevated levels of serum NTx indicate elevated bone resorption. Elevated bone resorption is the primary cause of agerelated bone loss and that low bone mass often results in osteopenia and is the major cause of osteoporosis. The measurement range is in nanoMoles (nm) Bone Collagen Equivalents (BCE).
Time frame: Week 12
Population: No Calcitriol group consists of Multivitamin arm and Exercise arm N=20; Calcitriol group consists of Calcitriol and Calcitriol+Exercise arms N=19\*\*~\*\* 2 subjects have missing data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Bone Resorption (Calcitriol) | 12.5 nm BCE | Standard Error 1.785 |
| Exercise | Bone Resorption (Calcitriol) | 15.0 nm BCE | Standard Error 1.113 |
p-value: 0.19ANCOVA
Primary
Bone Resorption (Exercise)
Bone Resorption using Serum NTx (Exercise comparison) Serum NTx level is used to aid in predicting skeletal response (bone mineral density) to antiresorptive therapy and in monitoring bone resorption changes following initiation of antiresorptive therapy. Elevated levels of serum NTx indicate elevated bone resorption. Elevated bone resorption is the primary cause of agerelated bone loss and that low bone mass often results in osteopenia and is the major cause of osteoporosis. The measurement range is in nanoMoles (NM) Bone Collagen Equivalents (BCE).
Time frame: Week 12
Population: No Exercise group consists of Multivitamin and Calcitriol arms N=20; Exercise group consists of Exercise and Calcitriol+Exercise arms N=19\*\*~\*\* 2 subjects have missing data for this outcome.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Bone Resorption (Exercise) | 13.8 nm BCE | Standard Error 1.656 |
| Exercise | Bone Resorption (Exercise) | 14.7 nm BCE | Standard Error 1.033 |
p-value: 0.86ANCOVA
Secondary
Body Mass Index (Calcitriol)
Body Mass Index(BMI) - (Calcitriol comparison) Measure Description: Body Mass Index (BMI) is a person's weight in kilograms divided by the square of height in meters. Values below 18.5 represent Underweight, 18.5 to 24.9 represent Normal or Healthy Weight, 25.0 to 29.9 represent Overweight and 30.0 and above represent Obese.
Time frame: Week 12
Population: No Calcitriol group consists of Multivitamin arm and Exercise arm N=16\*; Calcitriol group consists of Calcitriol and Calcitriol+Exercise arms N=20\*\* \* 4 subjects have missing data for this outcome.~\*\* 1 subject has missing data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Body Mass Index (Calcitriol) | 30.1 kg/m^2 | Standard Error 0.284 |
| Exercise | Body Mass Index (Calcitriol) | 30.1 kg/m^2 | Standard Error 0.161 |
p-value: 0.92t-test, 2 sided
Secondary
Body Mass Index (Exercise)
Body Mass Index (BMI) - (Exercise Comparison) Measure Description: Body Mass Index (BMI) is a person's weight in kilograms divided by the square of height in meters. Values below 18.5 represent Underweight, 18.5 to 24.9 represent Normal or Healthy Weight, 25.0 to 29.9 represent Overweight and 30.0 and above represent Obese.
Time frame: Week 12
Population: No Exercise group consists of Multivitamin and Calcitriol arms N=16\*; Exercise group consists of Exercise and Calcitriol+Exercise arms N=20\*\* \*4 subjects have missing data for this outcome.~\*\*1 subject has missing data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Body Mass Index (Exercise) | 30.0 kg/m^2 | Standard Error 0.312 |
| Exercise | Body Mass Index (Exercise) | 30.2 kg/m^2 | Standard Error 0.185 |
p-value: 0.38t-test, 2 sided
Secondary
Handgrip (kg) Strength - (Calcitriol)
Handgrip (kg) Strength - (Calcitriol comparison) Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. It is typically measured in kilograms or pounds and varies by sex and age. Normative data for females is AGE 35-39 --\> 20.3-34.1kg; AGE 40-44 --\> 18.9-32.7kg; AGE 45-49 --\> 18.6-32.4kg; AGE 50-54 --\> 18.1-31.9kg; AGE 55-59 --\> 17.7-31.5kg; AGE 60-64 --\> 17.2-31.0kg; AGE 65-69 --\> 15.4-27.2kg; AGE 70-99 --\> 14.7-24.5kg. Values less than the normal range are considered weak strength. Values greater than the normal range are considered strong strength.
Time frame: Week 12
Population: No Calcitriol group consists of Multivitamin arm and Exercise arm N=14\*; Calcitriol group consists of Calcitriol and Calcitriol+Exercise arms N=17\*\* \* 6 subjects have missing data for this outcome.~\*\* 4 subjects have missing data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Handgrip (kg) Strength - (Calcitriol) | 27.4 kg | Standard Error 1.441 |
| Exercise | Handgrip (kg) Strength - (Calcitriol) | 27.1 kg | Standard Error 0.804 |
p-value: 0.84t-test, 2 sided
Secondary
Handgrip (kg) Strength - (Exercise)
Handgrip (kg) Strength (Exercise comparison) Hand grip strength can be quantified by measuring the amount of static force that the hand can squeeze around a dynamometer. It is typically measured in kilograms or pounds and varies by sex and age. Normative data for females is AGE 35-39 --\> 20.3-34.1kg; AGE 40-44 --\> 18.9-32.7kg; AGE 45-49 --\> 18.6-32.4kg; AGE 50-54 --\> 18.1-31.9kg; AGE 55-59 --\> 17.7-31.5kg; AGE 60-64 --\> 17.2-31.0kg; AGE 65-69 --\> 15.4-27.2kg; AGE 70-99 --\> 14.7-24.5kg. Values less than the normal range are considered weak strength. Values greater than the normal range are considered strong strength.
Time frame: Week 12
Population: No Exercise group consists of Multivitamin and Calcitriol arms N=14\*; Exercise group consists of Exercise and Calcitriol+Exercise arms N=17\*\* \* 6 subjects have missing data for this outcome.~\*\* 4 subjects have missing data for this outcome.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| No Exercise | Handgrip (kg) Strength - (Exercise) | 26.6 kg | Standard Error 1.633 |
| Exercise | Handgrip (kg) Strength - (Exercise) | 27.8 kg | Standard Error 0.919 |
p-value: 0.16t-test, 2 sided