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An interim analysis demonstrated no benefit of high dose vitamin D when compared to standard dose vitamin D in the reduction or prevention of arthralgia
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This study is being done to look at the difference, if there is a difference between two different doses of Vitamin D and the reduction of joint/muscle pain (arthralgia)that is caused by taking anti-estrogen medications (aromatase inhibitors) by breast cancer patients. The investigators hope to learn if taking a higher dose of Vitamin D is a good way to prevent aromatase inhibitor arthralgia (AIA).
Treatments with anti-estrogen agents for hormone receptor positive breast cancer is the most efficacious of systemic therapies, with aromatase inhibitors (AI's) being considered the most active anti-estrogen therapy in early stage breast cancer. But, use of these treatments has been shown to cause musculoskeletal (joint/muscle) side effects that sometimes cause patients to discontinue the use of them. Also, Vitamin D deficiency is a well know cause of a wide array of musculoskeletal issues. There is evidence that Vitamin D supplementation may help prevent arthralgia while on AI's. Therefore, the investigators want to see if giving a higher dose of Vitamin D could decrease the incidence of AIA as compared to a standard dose of Vitamin D. The investigators believe that this could possibly result in patients continued treatment with AI therapy for hormone receptor positive breast cancer.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| High Dose Vitamin D ARM | Experimental | 50,000 IU Vitamin D supplement |
|
| 800 IU Vitamin D Supplement | Active Comparator | 800 IU Vitamin D Supplement |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 800 IU Vitamin D Supplement | Drug | Standard Dose |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater. | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Compliance With Anti-Cancer Treatment | We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated. | 52 Weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Grip Strength | Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52. | 52 weeks |
Inclusion Criteria:
Exclusion Criteria:
Prohibited Therapies: Patients may not take additional Calcium and Vitamin D aside from the study medications. Patients who are on cholestyramine or orlistat will not be allowed on the trial. Also, patients who are taking phenytoin or phenobarbital are not allowed on the trial either because of interaction between Vitamin D and anti-epileptic medications.
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| Name | Affiliation | Role |
|---|---|---|
| Mothaffar Rimawi, MD | Baylor College of Medicine | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Washington University / Siteman Cancer Center | St Louis | Missouri | 63110 | United States | ||
| Baylor College of Medicine |
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| ID | Title | Description |
|---|---|---|
| FG000 | High Dose Vitamin D ARM | 50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose |
| FG001 | 800 IU Vitamin D Supplement | 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Start Treament After Randomization |
|
| |||||||||||||||||||||
| Complete Study After Start |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | High Dose Vitamin D ARM | 50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose |
| BG001 | 800 IU Vitamin D Supplement | 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Number of Participants With Aromatase Inhibitor Induced Arthralgia (AIA) After 12 Weeks of Therapy | Aromatase Inhibitor Arthralgia (AIA) was assessed by a questionnaire that describe the level of pain experienced by the participant. The questionnaire asks 20 questions scored 0-3 in 8 categories of functioning: dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. An average composite score on the HAQ-II was calculated. The visual analog scale is the other major component of the HAQ-II, which we ask patients to mark where their pain lies on a horizontal line and we converts the number into a score from 0 to 3. For the purposes of this study, AIA will be defined as any of the following criteria: 1) increase in HAQ-II score from baseline by 0.2 or greater; or 2) increase in visual analog pain score by 0.3 or greater. | ITT population. All patients who were randomized in the study were included in the overall evaluation of response (intent-to-treat analysis). | Posted | Count of Participants | Participants | 12 weeks |
|
56 weeks. Adverse events experienced by participants were collected and reported from initiation of study medication, throughout the study (52 weeks treatment), and within 30 days of the last dose of study medication.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | High Dose Vitamin D ARM | 50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Skin infection | Infections and infestations | CTCAE v4.0 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Hypothyroidism | Endocrine disorders | CTCAE v4.0 | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Tao Wang | Baylor College of Medicine | 7137985388 | taow@bcm.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jul 14, 2015 | Jan 31, 2019 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
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| 50,000 IU Vitamin D supplement |
| Drug |
High Dose |
|
| Association Between Vitamin D Levels Changes and Treatment. | Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated. | 12 weeks |
| Houston |
| Texas |
| 77030 |
| United States |
| NOT COMPLETED |
|
|
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Serum 25-hydroxyvitamin D level | Mean | Standard Deviation | ng/mL |
|
| OG000 |
| High Dose Vitamin D ARM |
50,000 IU Vitamin D supplement 50,000 IU Vitamin D supplement: High Dose |
| OG001 | 800 IU Vitamin D Supplement | 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose |
|
|
|
| Secondary | Compliance With Anti-Cancer Treatment | We checked compliance of aromatase inhibitor therapy during the study by reviewing the patient's use of AI drug. This will be done by counting remaining pills in patient's bottles of AI at 52 weeks. A percentage of the number of pills were actually taken of the number of pills should be taken was calculated. | Compliance was assessed at week 52. Only 14 patients have compete the data collection. Form was not completed due to not starting the treatment, or not finishing the treatment, or no source data. | Posted | Mean | Standard Deviation | percentage of pills taken | 52 Weeks |
|
|
|
| Secondary | Association Between Vitamin D Levels Changes and Treatment. | Patients' serum 25-hydroxyvitamin D level were tested at baseline and week 12. The changes between baseline and week 12 were calculated. | Patients who had serum 25-hydroxyvitamin D level tested at baseline and week 12 were included in the analysis. | Posted | Mean | Standard Deviation | ng/mL | 12 weeks |
|
|
|
|
| Other Pre-specified | Grip Strength | Exploratory Endpoints For each patient on the study, grip strength will be correlated with AIA score using Spearman correlation at three time points throughout the study - baseline, week 12, and week 52. | Not Posted | 52 weeks | Participants |
| 0 |
| 44 |
| 2 |
| 44 |
| 35 |
| 44 |
| EG001 | 800 IU Vitamin D Supplement | 800 IU Vitamin D Supplement 800 IU Vitamin D Supplement: Standard Dose | 0 | 43 | 0 | 43 | 36 | 43 |
| Renal and urinary disorders - Other, specify | Renal and urinary disorders | CTCAE v4.0 | Systematic Assessment |
|
| Constipation | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE v4.0 | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE v4.0 | Systematic Assessment |
|
| Pain | General disorders | CTCAE v4.0 | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment |
|
| Arthritis | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | CTCAE v4.0 | Systematic Assessment |
|
| headache | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Peripheral sensory neuropathy | Nervous system disorders | CTCAE v4.0 | Systematic Assessment |
|
| Anxiety | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment |
|
| Depression | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment |
|
| Insomnia | Psychiatric disorders | CTCAE v4.0 | Systematic Assessment |
|
| vaginal dryness | Reproductive system and breast disorders | CTCAE v4.0 | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE v4.0 | Systematic Assessment |
|
| Hot flashes | Vascular disorders | CTCAE v4.0 | Systematic Assessment |
|
| Hypertension | Vascular disorders | CTCAE v4.0 | Systematic Assessment |
|
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| D017437 |
| Skin and Connective Tissue Diseases |