Joint Pain, Muscle Pain
Conditions
Brief summary
The Purpose of this study is to determine whether vitamin D3 supplements will decrease the muscle and bone pain that are reported by women who take Aromatase Inhibitors.
Detailed description
This project will determine the efficacy of vitamin D3 supplements for reducing side effects of treatment with aromatase inhibitors in women with a history of breast cancer that have no evidence of current disease. The aromatase inhibitors (AI) have become a critical component of adjuvant therapy for this population, but they cause bone pain, joint pain, joint stiffness, and muscle weakness in approximately 40% of patients. These symptoms, referred to as aromatase inhibitor-associated musculoskeletal symptoms (AIMSS), decrease quality of life and medication adherence. Identifying effective ways to decrease these symptoms may allow for longer and more adherent medication use and thus may improve disease-free survival. We hypothesize that vitamin D3 may decrease symptoms associated with the use of aromatase inhibitors.
Interventions
DRUGVitamin D3
Cholecalciferol capsule, 4000IU, daily for 6 months
Sponsors
University of Minnesota
University of Southern California
HealthPartners Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age ≥ 18 years * Women with a history of stage I-IIIa invasive breast cancer * History of hormone-receptor positive cancer (either ER + or PR + or both) * Are prescribed and are taking anastrozole, letrozole or exemestane for at least one month and have at least 7 months of AI treatment remaining * Are experiencing AIMSS
Exclusion criteria
* Unable to read or understand English * History of psychiatric disability affecting informed consent or compliance with drug intake * Malabsorption syndrome or inability to take oral medication * Has less than 7 months of AI therapy remaining
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale | baseline to 6 months | The MS subscale is a self-reported measure on a scale of 0 to 4, with lower score indicating less arthralgia/myalgia |
| Change in Hand Grip Strength | baseline to 6 months | — |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum Estradiol Concentrations | baseline and 6 months | — |
| Change in Steady State Concentrations of Serum Anastrazole and Letrozole | baseline to 6 months | Difference in steady state concentrations in plasma from baseline to 6 months |
| Change in PROMIS Physical Functioning Questionnaire | baseline to 6 months | PROMIS measures physical functioning on the short form and higher scores reflect better physical functioning with 10 questions on daily activities of life on a Likert scale ranging from 5 (no problem performing activity) to 1 (cannot do activity). Range on this measure is from 50 (best)-10 (worst). |
| Vitamin D Binding Protein Genotype | Baseline | — |
| Whole Body Bone Mineral Density | From Baseline and 6 months of D3 supplementation | GLM Mean and standard deviation of Whole Body Bone Mineral Density (grams/cm2) of Trial Participants by Treatment Arm after controlling for bisphosphonate use |
| Average Percent Adherence to Vitamin D Interventio | average for all study ppts for: screening to baseline; baseline to 3 months; 3 month to 6 months | adherence measured with pill counts for the vitamin D at predesignated study timepoints: baseline (after run-in), 3 months and 6 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3 4000 IU Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months | 57 |
| Vitamin D3 600 IU Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months | 56 |
| Total | 113 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lack of Efficacy | 0 | 2 |
| Overall Study | started an excluded medication | 0 | 1 |
Baseline characteristics
| Characteristic | Vitamin D3 4000 IU | Vitamin D3 600 IU | Total |
|---|---|---|---|
| Age, Continuous | 61.4 years STANDARD_DEVIATION 8.4 | 60.3 years STANDARD_DEVIATION 9.3 | 60.9 years STANDARD_DEVIATION 8.8 |
| Region of Enrollment United States | 57 participants | 56 participants | 113 participants |
| Sex: Female, Male Female | 57 Participants | 56 Participants | 113 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 35 / 57 | 32 / 56 |
| serious Total, serious adverse events | 0 / 57 | 0 / 56 |
Outcome results
Primary
Change in Hand Grip Strength
Time frame: baseline to 6 months
Population: only data from participants that were collected at both time points is included
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 4000 IU | Change in Hand Grip Strength | 1.8 pounds | Standard Deviation 10.6 |
| Vitamin D3 600 IU | Change in Hand Grip Strength | 1.0 pounds | Standard Deviation 7.6 |
Primary
Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale
The MS subscale is a self-reported measure on a scale of 0 to 4, with lower score indicating less arthralgia/myalgia
Time frame: baseline to 6 months
Population: Only participants who provided data at both time points are included
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 4000 IU | Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale | -0.2 units on a scale | Standard Deviation 0.7 |
| Vitamin D3 600 IU | Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale | -0.5 units on a scale | Standard Deviation 0.9 |
p-value: 0.38ANOVA
Secondary
Average Percent Adherence to Vitamin D Interventio
adherence measured with pill counts for the vitamin D at predesignated study timepoints: baseline (after run-in), 3 months and 6 months
Time frame: average for all study ppts for: screening to baseline; baseline to 3 months; 3 month to 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vitamin D3 4000 IU | Average Percent Adherence to Vitamin D Interventio | 95 % of adherence for each treatment arm |
| Vitamin D3 600 IU | Average Percent Adherence to Vitamin D Interventio | 95 % of adherence for each treatment arm |
Secondary
Change in PROMIS Physical Functioning Questionnaire
PROMIS measures physical functioning on the short form and higher scores reflect better physical functioning with 10 questions on daily activities of life on a Likert scale ranging from 5 (no problem performing activity) to 1 (cannot do activity). Range on this measure is from 50 (best)-10 (worst).
Time frame: baseline to 6 months
Population: only data from participants with measures at both time points are included
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 4000 IU | Change in PROMIS Physical Functioning Questionnaire | 0.6 units on a scale | Standard Deviation 4.9 |
| Vitamin D3 600 IU | Change in PROMIS Physical Functioning Questionnaire | 1.7 units on a scale | Standard Deviation 6.9 |
Secondary
Change in Steady State Concentrations of Serum Anastrazole and Letrozole
Difference in steady state concentrations in plasma from baseline to 6 months
Time frame: baseline to 6 months
Population: Only study participants with baseline and 6 month blood samples available were analyzed
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Vitamin D3 4000 IU | Change in Steady State Concentrations of Serum Anastrazole and Letrozole | anastrozole | -1.31 mg/L | Standard Deviation 10.67 |
| Vitamin D3 4000 IU | Change in Steady State Concentrations of Serum Anastrazole and Letrozole | letrozole | 2.16 mg/L | Standard Deviation 9.69 |
| Vitamin D3 600 IU | Change in Steady State Concentrations of Serum Anastrazole and Letrozole | anastrozole | 2.4 mg/L | Standard Deviation 5.36 |
| Vitamin D3 600 IU | Change in Steady State Concentrations of Serum Anastrazole and Letrozole | letrozole | -0.83 mg/L | Standard Deviation 16.4 |
Secondary
Serum Estradiol Concentrations
Time frame: baseline and 6 months
Population: only participants whose serum was obtained at both time points are included
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Vitamin D3 4000 IU | Serum Estradiol Concentrations | 6 months | 2.94 pg/ml | Standard Error 0.16 |
| Vitamin D3 4000 IU | Serum Estradiol Concentrations | Baseline | 2.83 pg/ml | Standard Error 0.1 |
| Vitamin D3 600 IU | Serum Estradiol Concentrations | Baseline | 2.77 pg/ml | Standard Error 0.1 |
| Vitamin D3 600 IU | Serum Estradiol Concentrations | 6 months | 3.0 pg/ml | Standard Error 0.12 |
Secondary
Vitamin D Binding Protein Genotype
Time frame: Baseline
Population: Due to funding limitations, this secondary aim was not collected and analyzed in these groups
Secondary
Whole Body Bone Mineral Density
GLM Mean and standard deviation of Whole Body Bone Mineral Density (grams/cm2) of Trial Participants by Treatment Arm after controlling for bisphosphonate use
Time frame: From Baseline and 6 months of D3 supplementation
| Arm | Measure | Value (GEOMETRIC_LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 4000 IU | Whole Body Bone Mineral Density | 1.1 gm/cm2 | Standard Deviation 0.12 |
| Vitamin D3 600 IU | Whole Body Bone Mineral Density | 1.12 gm/cm2 | Standard Deviation 0.13 |