Vitamin D3 Effects on Musculoskeletal Symptoms With Use of Aromatase Inhibitors

Phase 2 Study Vitamin D3 Effects on Musculoskeletal Symptoms With Use of Aromatase Inhibitors

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.

Study Overview

• Status: Completed
• Conditions: Joint Pain; Muscle Pain
• Intervention / Treatment: Drug: Vitamin D3; Drug: Vitamin D3

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.

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55416
      • Park Nicollet Frauenshuh Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vitamin D3 4000 IU	Drug: Vitamin D3; Cholecalciferol capsule, 4000IU, daily for 6 months; Drug: Vitamin D3; cholecalciferol capsule, 600 IU, daily for 6 months
Active Comparator: Vitamin D3 600 IU	Drug: Vitamin D3; Cholecalciferol capsule, 4000IU, daily for 6 months; Drug: Vitamin D3; cholecalciferol capsule, 600 IU, daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	baseline to 6 months
Change in Hand Grip Strength		baseline to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	baseline to 6 months
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	average for all study ppts for: screening to baseline; baseline to 3 months; 3 month to 6 months
Serum Estradiol Concentrations		baseline and 6 months
Change in Steady State Concentrations of Serum Anastrazole and Letrozole	Difference in steady state concentrations in plasma from baseline to 6 months	baseline to 6 months
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	From Baseline and 6 months of D3 supplementation
Vitamin D Binding Protein Genotype		Baseline

Collaborators and Investigators

• Sponsor: HealthPartners Institute
• Collaborators: University of Southern California; University of Minnesota
• Investigators: Principal Investigator: Alice C. Shapiro, PhD RD, Park Nicollet Health Services

Publications and helpful links

General Publications

• Shapiro AC, Adlis SA, Robien K, Kirstein MN, Liang S, Richter SA, Lerner RE. Randomized, blinded trial of vitamin D3 for treating aromatase inhibitor-associated musculoskeletal symptoms (AIMSS). Breast Cancer Res Treat. 2016 Feb;155(3):501-12. doi: 10.1007/s10549-016-3710-6. Epub 2016 Feb 11. Erratum In: Breast Cancer Res Treat. 2016 Jun;157(2):403.

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): March 1, 2015

Study Registration Dates

• First Submitted: December 12, 2011
• First Submitted That Met QC Criteria: January 9, 2012
• First Posted (Estimate): January 12, 2012

Study Record Updates

• Last Update Posted (Actual): June 18, 2019
• Last Update Submitted That Met QC Criteria: May 28, 2019
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Pain; Neurologic Manifestations; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Neuromuscular Diseases; Musculoskeletal Pain; Arthralgia; Myalgia; Physiological Effects of Drugs; Micronutrients; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol; Vitamins; Ergocalciferols
• Other Study ID Numbers: 03962-10C

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No