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Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D) (SAFE-D)

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ClinicalTrials.gov Identifier: NCT02186015
Recruitment Status : Completed
First Posted : July 10, 2014
Last Update Posted : August 1, 2019
Sponsor:
Information provided by (Responsible Party):
Patricia Sheean, Loyola University

Brief Summary:

Background: Several clinical trials are underway to investigate if variable forms of vitamin D (D2 vs. D3) prescribed at different doses (10,000-50,000 IUs/week) can improve the side-effects associated with treatment for estrogen receptor positive (ER+) breast cancer, specifically aromatase inhibitors (AIs.) Presumably for generalizability and potential safety purposes, these trials predominantly exclude women with metastatic breast cancer (MBC); a rapidly expanding sector of the cancer survivor population who experience significant treatment-related side-effects. Evaluation of the safety of vitamin D3 supplementation is crucial since supplementation can lead to high calcium and importantly, in lab studies have shown that vitamin D3 affects a gene that increases estrogen production. To assure that vitamin D3 does not affect the clinical effects of anti-estrogen therapies, the effect of vitamin D3 supplements on estrogen production requires an evaluation that further explores and defines its potential role in symptom management for this population.

Objectives: This pilot study will evaluate the feasibility of vitamin D3 supplementation in women with MBC, providing much needed data on the preliminary safety and efficacy of this treatment in this patient population. This study will determine: 1) if weekly supplementation of high dose vitamin D3 increases serum vitamin D levels without adverse effects related to such therapy (primary aim); 2) the effects of vitamin D3 supplementation on symptom management (secondary aim); and 3) if vitamin D3 supplementation is associated with improved inflammation (exploratory aim.)

Methods: This is an 8 week "proof of concept" study to monitor important laboratory parameters and to assess potential effects on short-term outcomes. Adult, female patients (>=18 years) with ER+ MBC (Stage IV) of any race/ethnicity and a history of vitamin D < 30 mg/dl will be recruited from within and around LUMC. Following current clinical practice guidelines, eligible participants will receive 50,000 IUs of vitamin D3 weekly for 8 weeks. Laboratory values, muscle function and inflammation will be examined pre- and post-supplementation, while symptoms (e.g., pain, sleep, fatigue, mood, and overall quality of life) will be assessed at baseline, 4 and 8 weeks post-supplementation. We will assess if increases in vitamin D are associated with clinically significant changes in serum estradiol, improvements in symptoms and QOL, and decreased inflammation, controlling for sunlight exposure, diet, physical activity and body composition.


Condition or disease Intervention/treatment Phase
Adult Women Metastatic Breast Cancer Estrogen Receptor Positive Drug: Cholecalciferol Phase 2

Detailed Description:

Study Aims

Several clinical trials are underway to investigate if vitamin D2 or D3 provided at various doses (10,000-50,000 IUs/week) can improve the side-effects associated with anti-estrogen therapies, specifically aromatase inhibitors (AIs). However, these current trials use variable forms of vitamin D and predominantly include women with Stage I-III disease, excluding women with metastatic breast cancer. Evaluation of the safety of vitamin D3 supplementation is crucial since supplementation can lead to hypercalcemia and importantly, in vitro studies have shown that vitamin D3 influences the transcription of a gene that increases estrogen production.27,28 To assure that vitamin D3 does not abrogate the clinical effects of anti-estrogen therapies, the effect of vitamin D3 supplementation on estrogen production requires evaluation. Therefore, the overarching goal of this pilot study is to evaluate the safety, feasibility and efficacy of vitamin D3 supplementation in women with MBC. We will address and test the following aims and hypotheses, respectively:

Aim 1: To determine if weekly supplementation of 50,000 IUs of vitamin D3 raises serum levels of 25(OH)D to >30 mg/dl without adverse effects.

Hypothesis 1: Women who are compliant with vitamin D3 supplementation, as evidenced by normalization (>30 mg/dl) or increases in their serum 25(OH)D levels, will not experience significant changes in serum calcium, parathyroid hormone or serum estradiol levels.

Aim 2: To determine the effect of vitamin D3 supplementation on symptom management.

Hypothesis 2: Women who achieve serum concentrations of 25 (OH)D ≥30 mg/dl or experience significant increases in 25(OH)D will exhibit improvements in pain, fatigue, sleep, mood, muscle function and overall quality of life.

Exploratory Aim: To explore the mechanistic effects of vitamin D3 supplementation on inflammatory markers and its potential association with symptom management.

Summary: Evidence from studies involving early stage breast cancer participants confirms that musculoskeletal pain, endocrine related symptoms and mood disturbances are commonly associated with breast cancer treatment, particularly hormone deprivation therapies. The high prevalence of vitamin D deficiency/insufficiency among breast cancer survivors is well accepted and further hypothesized to aggravate treatment-related side effects, particularly arthralgias. Women with MBC are excluded from the majority of on-going vitamin D supplementation trials for safety and generalizability purposes. However, novel therapies are continuing to improve and prolong the lives of these women, resulting in a rapidly expansive group of breast cancer survivors. While vitamin D supplementation is prescribed to correct an underlying nutrient deficiency in the clinical context of preserving bone health, emerging evidence suggests it may have more systemic effects. Thus, vitamin D repletion/supplementation has profound potential implications for women with MBC, whose primary goal of treatment is to minimize the side-effects of treatment in support of optimal quality of life. This study reflects a highly innovative, yet simple therapy that could ultimately provide these survivors with a much needed evidence-based supportive care strategies.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 43 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety, Feasibility and Efficacy of Vitamin D Supplementation in Women With Metastatic Breast Cancer (SAFE-D)
Study Start Date : February 2015
Actual Primary Completion Date : March 8, 2017
Actual Study Completion Date : November 9, 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Cholecalciferol
All participants will receive 50,000 IU weekly supplementation of cholecalciferol for 8 weeks.
Drug: Cholecalciferol
Enrolled women will receive 50,000 IU weekly supplementation of cholecalciferol for 8 weeks.
Other Names:
  • Vitamin D3
  • Vitamin D




Primary Outcome Measures :
  1. Serum 25(OH)D [ Time Frame: 0 and 8 weeks ]
    Laboratory serum value of 25(OH)D at week 0 versus week 8


Secondary Outcome Measures :
  1. Beck Pain Scale [ Time Frame: 0, 4, and 8 weeks ]
    Assessment of pain using the Beck Pain Scale at weeks 0, 4, and 8

  2. fatigue [ Time Frame: 0, 4, and 8 weeks ]
    Assessment of fatigue using the Piper Fatigue Scale at weeks 0, 4, and 8

  3. mood [ Time Frame: 0,4, and 8 weeks ]
    Assessment of mood using the Hospital Anxiety and Depression Scale and the Patient Health Questionnaire 8 at weeks 0,4 and 8

  4. Muscle function [ Time Frame: 0 and 8 weeks ]
    Assessment of muscle function using a hand dynamometer at weeks 0 and 8

  5. Sleep [ Time Frame: 0, 4, and 8 weeks ]
    Assessment of sleep using the Pittsburgh Sleep Quality Index at weeks 0,4, and 8

  6. functional assessment of cancer therapy- breast and endocrine symptoms [ Time Frame: 0,4 and 8 weeks ]
    Assessment of quality of life using the functional assessment of cancer therapy- breast and endocrine symptoms at weeks 0,4 and 8



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Metastatic breast cancer (Stage IV)
  2. Histologically confirmed estrogen receptor positive disease
  3. Female
  4. Serum 25(OH) <30 ng/ml
  5. Age ≥ 18 years
  6. Pre or post-menopausal
  7. ECOG Performance status 0-2
  8. Adequate organ function as defined as GFR> 30 mls/min and serum calcium ≤ 10.4 mg/dl
  9. Any race/ethnicity
  10. English speaking
  11. No changes to MBC treatments within 30 days of enrollment and/or deemed clinically stable by their treating physician
  12. Willingness to sign a written informed consent and complete questionnaires
  13. Cease ingestion of vitamin D supplementation not study related

Exclusion Criteria:

  1. Women with Stage I-III breast cancer
  2. Serum 25(OH)D levels ≥ 30 ng/ml
  3. Untreated CNS involvement
  4. History of kidney stones
  5. History of renal failure
  6. History of hyperparathyroidism
  7. History of hypersensitivity to vitamin D
  8. Non-English speaking
  9. Currently pregnant or lactating, or anticipating pregnancy
  10. Unwilling to cease ingestion of calcium supplements (>1000 mg/d)
  11. Unwilling or unable to complete informed consent or study questionnaires
  12. Psychiatric or other clinical conditions that preclude study compliance
  13. Other important medical or safety considerations at the discretion of the investigator and/or study physician, including non-compliance with the study therapy or other activities

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02186015


Locations
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United States, Illinois
Loyola University Medical Center
Maywood, Illinois, United States, 60153
Sponsors and Collaborators
Loyola University
Investigators
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Principal Investigator: Patricia M Sheean, Ph.D., R.D. Loyola University
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Patricia Sheean, Research Associate, Loyola University
ClinicalTrials.gov Identifier: NCT02186015    
Other Study ID Numbers: 206519
First Posted: July 10, 2014    Key Record Dates
Last Update Posted: August 1, 2019
Last Verified: July 2019
Keywords provided by Patricia Sheean, Loyola University:
Metastatic Breast Cancer
MBC
Vitamin D Supplementation
Symptom Management
Additional relevant MeSH terms:
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Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents