A Study of High-Dose Vit D Versus Standard of Care Vit D Supplementation

A Randomized, Open-label Study of High-Dose Vitamin D Versus Standard of Care Vitamin D Supplementation to Evaluate the Impact on Bone Health in Young Women With Early Stage Breast Cancer

This is a randomized study evaluating the effects of early intensive vitamin D supplementation compared to standard of care vitamin D supplementation on bone health over an 18 month period.

Study Overview

• Status: Completed
• Conditions: Breast Cancer; Osteoporosis; Breast
• Intervention / Treatment: Dietary supplement: High Dose Vitamin D; Dietary supplement: Standard of Care Vitamin D

Detailed Description

This is a randomized, open-label study designed to evaluate the effect of high dose vitamin D versus standard of care vitamin D supplementation on bone health and arthralgias. The randomization will be stratified by hormone receptor status (positive versus negative). The primary objective is to compare the effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on bone health, as measured by percent change from baseline in bone mineral density (g/cm2), in young women with non-metastatic breast cancer who receive systemic therapy.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Charlotte, North Carolina, United States, 28204
      • Levine Cancer Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

Subject must meet all of the following applicable inclusion criteria to participate in this study:

1. Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
2. Age; 45 years at the time of consent
3. Female
4. Histological or cytological confirmation of breast cancer clinical or pathologic stages 0-III

5. Patient has been recommended to initiate systemic therapy for breast cancer. It is preferable for patient to enroll prior to systemic therapy initiation. However, enrollment will be allowed if systemic therapy has been initiated within 4 weeks prior to enrollment (randomization).

   Note: Patients who undergo only surgery and/or radiotherapy alone would not qualify for the study.

6. Systemic therapy for breast cancer is planned
7. As determined by the enrolling physician, ability of the subject to understand and comply with study procedures for the entire length of the study
8. Previous vitamin D supplementation allowed, as long as patient is agreeable to stop previous dosing at the time of trial enrollment, to comply with trial procedures including a baseline 25(OH)D level, and is otherwise determined to be appropriate for enrollment

Exclusion Criteria

Subjects meeting any of the criteria below may not participate in the study:

1. Uncontrolled intercurrent illness/medical condition or psychiatric illness/social situations that would limit compliance with study requirements as determined by the Investigator
2. Patients will undergo breast surgery and/or radiotherapy alone without planned neoadjuvant and/or adjuvant anti-cancer drug therapy.
3. Baseline 25(OH)D level <10ng/mL or >80ng/mL
4. Baseline serum corrected calcium level of >10.3mg/dL
5. Bone mineral density less than the expected range for age on baseline DEXA scan (defined as Z-score </= -2.0)
6. Breast cancer with distant metastasis
7. History of previous breast cancer
8. Postmenopausal, as confirmed by the lack of menses >/=12 months and/or ovarian function laboratories (estradiol, FSH) consistent with menopause (if any of two values outside of menopausal range and subject had menses within 12 months, subject would be considered perimenopausal or premenopausal and therefore eligible for enrollment)
9. Pregnancy or lactation
10. History of bone disease, including Paget's bone disease or osteomalacia
11. Concurrent rheumatoid or other inflammatory arthritis
12. Concurrent or prior treatment with bisphosphonates
13. Use of oral corticosteroids within the last 30 days prior to randomization
14. Concurrent treatment for thyroid deficiency
15. BMI <18.5
16. Currently receiving treatment for tuberculosis, or planning to receive treatment for tuberculosis during breast cancer treatments
17. History of another primary cancer that required systemic treatment within the last 5 years
18. Any of the following kidney diseases at the time of randomization: active chronic kidney disease >/= stage 3, history of kidney stones, sarcoidosis
19. Gastrointestinal disease that would limit the absorption of pill therapy (i.e. celiac disease, gastric bypass surgery)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Vit D; High Dose Vitamin D	Dietary supplement: High Dose Vitamin D; High dose vitamin D: Subjects will receive 50,000 IU vitamin D2 weekly x 16 weeks followed by 4,000 IU of vitamin D3 daily with a goal 25(OH)D level of ≥45 but ≤80 ng/mL.
Active Comparator: SOC Vit D; Standard of Care Vitamin D	Dietary supplement: Standard of Care Vitamin D; Standard of Care Vitamin D: Vitamin D will be supplemented to 25(OH)D levels, with a goal 25(OH)D level of >30 ng/mL according to Endocrine Society Practice Guidelines.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent change from baseline in bone mineral density (g/cm^2) from baseline to the Year 1 DEXA scan	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on bone health, as measured by percent change from baseline in bone mineral density (g/cm2) to the Year 1 planned DEXA scan, in young women with non-metastatic breast cancer who receive systemic therapy.	15 months (12 plus a +3 month calendar window)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
25(OH) D level over time	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm 25(OH) D levels in young women with non-metastatic breast cancer who receive systemic therapy.	18 months
PRAI questionnaire results over time	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on PRAI questionnaire results in young women with non-metastatic breast cancer who receive systemic therapy.	18 months
Overall satisfaction with pain control over time	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on overall satisfaction with pain control in young women with non-metastatic breast cancer who receive systemic therapy.	18 months
Skeletal complications over time	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on skeletal complications in young women with non-metastatic breast cancer who receive systemic therapy.	18 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D administration	Descriptively summarize vitamin D administration for the high dose vitamin D arm and for the current standard vitamin D treatment administration algorithm in young women with non-metastatic breast cancer who receive systemic therapy.	18 months
Adverse events of special interest	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on adverse events of special interest (vitamin D related headaches, irritability, spasticity, nausea, vomiting, and hypercalcemia) in young women with non-metastatic breast cancer who receive systemic therapy.	19 months
Adverse events of special interest leading to vitamin D dose modifications or discontinuations	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on adverse events of special interest (vitamin D related headaches, irritability, spasticity, nausea, vomiting, and hypercalcemia) that results in vitamin D dose modifications or discontinuations in young women with non-metastatic breast cancer who receive systemic therapy.	18 months
Serious adverse events	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on serious adverse events in young women with non-metastatic breast cancer who receive systemic therapy.	19 months
Treatment discontinuation due to vitamin D non-compliance	Compare effect of high dose vitamin D to the current standard vitamin D treatment administration algorithm on treatment discontinuation due to vitamin D intake non-compliance.	18 months

Collaborators and Investigators

• Sponsor: Wake Forest University Health Sciences
• Collaborators: Atrium Health Levine Cancer Institute
• Investigators: Principal Investigator: Arielle Heeke, MD, Wake Forest University Health Sciences

Study record dates

Study Major Dates

• Study Start (Actual): September 16, 2021
• Primary Completion (Actual): February 21, 2024
• Study Completion (Actual): August 15, 2024

Study Registration Dates

• First Submitted: August 17, 2021
• First Submitted That Met QC Criteria: August 17, 2021
• First Posted (Actual): August 23, 2021

Study Record Updates

• Last Update Posted (Actual): July 23, 2025
• Last Update Submitted That Met QC Criteria: July 18, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: Bone Density
• Additional Relevant MeSH Terms: Bone Diseases; Musculoskeletal Diseases; Neoplasms by Site; Neoplasms; Metabolic Diseases; Skin Diseases; Breast Diseases; Bone Diseases, Metabolic; Breast Neoplasms; Osteoporosis; Calcium-Regulating Hormones and Agents; Physiological Effects of Drugs; Bone Density Conservation Agents; Micronutrients; Vitamin D; Ergocalciferols; Vitamins; Cholecalciferol
• Other Study ID Numbers: LCI-BRE-VITD-001 (Other Identifier: LCI); 00055909 (Other Identifier: Advarra IRB)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No