Placebo-controlled Trial With Vitamin D to Prevent Worsening/Relieve Aromatase Inhibitor-induced Musculoskeletal Symptoms in Breast Cancer Patients

Study Overview
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Brief Summary
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The third generation oral aromatase inhibitors (AIs) are increasingly being used in the management of estrogen receptor positive breast cancer. One of the issues related with administration of oral AIs is their side effects, particularly on the musculoskeletal system. Although the prevalence and importance of arthralgia and myalgia occurring in BC patients receiving adjuvant AIs are evident, the mechanisms clearly explaining these invalidating symptoms are unknown. In this project, we aim to unravel the interaction between vitamin D and musculoskeletal adverse events experienced by AI users. We will also evaluate how vitamin D supplementation affects AI-induced musculoskeletal symptoms in breast cancer patients, by means of a randomized placebo-controlled double blind clinical trial. We will assess changes in the musculoskeletal system by using magnetic resonance imaging of joints, hand grip strength and also monitor serum IGF-I and estrogen levels together with bone resorption and formation markers.

Official Title
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Placebo-controlled Trial With Vitamin D to Prevent Worsening/Relieve Aromatase Inhibitor-induced Musculoskeletal Symptoms in Breast Cancer Patients

Conditions
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Breast Cancer, Musculoskeletal Disease

Intervention / Treatment
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* Drug: Vitamin D3
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal status Currently being treated with an AI in the adjuvant setting (minimum for 8 weeks) AIMSS as determined by new or worsened musculoskeletal complaints following AI therapy Vitamin D deficiency (<30ng/ml) Caucasian Exclusion Criteria: Hormone replacement therapy last 6 months Current use or in the last 12 months of bisphosphonates Tamoxifen use in last 6 months History of kidney stones History of hypercalcemia/hypercalciuria or hyperthyroidism Paget's disease of the bone Current use of Digitalis/digoxin or thiazide diuretics Current use of vitamin D (or multivitamin) supplementation should be stopped

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: vitamin D3<br>1000 mg Ca2+/800IU vitamin D3 daily + 25 000IU vitamin D3 weekly during 6 months | Drug: Vitamin D3<br>* ampoule<br>|
| Placebo Comparator: Placebo<br>1000 mg Ca2+/ 800IU vitamin D3 daily + 25000IU placebo every week during 6 months | Drug: Placebo<br>* ampoule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in musculoskeletal pain and 250HD levels |  | 3 monthly during one year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline in bone parameters, estrogen and IGF-I levels and fluid accumulation and tendon pathologies, as seen on MRI |  | 3 monthly during 1 year, MRI at baseline and 3 months |