Vitamin D3 Effects on Musculoskeletal Symptoms With Use of Aromatase Inhibitors

• Sponsor: HealthPartners Institute (Other)
• Overall Status: Completed
• CT.gov ID: NCT01509079
• Collaborator: University of Minnesota (Other), University of Southern California (Other)
• Enrollment: 116
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 3.2

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Muscle Pain; Joint Pain	Drug: Vitamin D3; Drug: Vitamin D3	Phase 2

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 Design

• Study Type: Interventional
• Actual Enrollment: 116 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Supportive Care
• Official Title: Phase 2 Study Vitamin D3 Effects on Musculoskeletal Symptoms With Use of Aromatase Inhibitors
• Study Start Date: Mar 1, 2012
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Mar 1, 2015

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale [baseline to 6 months]

   The MS subscale is a self-reported measure on a scale of 0 to 4, with lower score indicating less arthralgia/myalgia

2. Change in Hand Grip Strength [baseline to 6 months]

Secondary Outcome Measures

1. Change in PROMIS Physical Functioning Questionnaire [baseline to 6 months]

   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).

2. Average Percent Adherence to Vitamin D Interventio [average for all study ppts for: screening to baseline; baseline to 3 months; 3 month to 6 months]

   adherence measured with pill counts for the vitamin D at predesignated study timepoints: baseline (after run-in), 3 months and 6 months

3. Serum Estradiol Concentrations [baseline and 6 months]

4. Change in Steady State Concentrations of Serum Anastrazole and Letrozole [baseline to 6 months]

   Difference in steady state concentrations in plasma from baseline to 6 months

5. Whole Body Bone Mineral Density [From Baseline and 6 months of D3 supplementation]

   GLM Mean and standard deviation of Whole Body Bone Mineral Density (grams/cm2) of Trial Participants by Treatment Arm after controlling for bisphosphonate use

6. Vitamin D Binding Protein Genotype [Baseline]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Park Nicollet Frauenshuh Cancer Center	Minneapolis	Minnesota	United States	55416

Sponsors and Collaborators

• HealthPartners Institute
• University of Minnesota
• University of Southern California

Investigators

• Principal Investigator: Alice C. Shapiro, PhD RD, Park Nicollet Health Services

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: HealthPartners Institute
• ClinicalTrials.gov Identifier: NCT01509079
• Other Study ID Numbers: 03962-10C
• First Posted: Jan 12, 2012
• Last Update Posted: Jun 18, 2019
• Last Verified: Oct 1, 2015

• Additional relevant MeSH terms: Arthralgia; Myalgia; Vitamin D; Ergocalciferols; Cholecalciferol; Vitamins

Study Results

Participant Flow

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Period Title: Overall Study
STARTED	57	59
COMPLETED	57	56
NOT COMPLETED	0	3

Baseline Characteristics

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU	Total
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months	Total of all reporting groups
Overall Participants	57	56	113
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61.4 (8.4)	60.3 (9.3)	60.9 (8.8)
Sex: Female, Male (Count of Participants)
Female	57 100%	56 100%	113 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	57 100%	56 100%	113 100%

Outcome Measures

1. Primary Outcome

Title	Change in Musculoskeletal Symptom Sub-scale on the Breast Cancer Prevention Trial Symptom Scale
Description	The MS subscale is a self-reported measure on a scale of 0 to 4, with lower score indicating less arthralgia/myalgia
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

Only participants who provided data at both time points are included

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	57	55
Mean (Standard Deviation) [units on a scale]	-0.2 (0.7)	-0.5 (0.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vitamin D3 4000 IU, Vitamin D3 600 IU
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.38
	Comments
	Method	ANOVA
	Comments

2. Primary Outcome

Title	Change in Hand Grip Strength
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

only data from participants that were collected at both time points is included

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	54	53
Mean (Standard Deviation) [pounds]	1.8 (10.6)	1.0 (7.6)

3. Secondary Outcome

Title	Change in PROMIS Physical Functioning Questionnaire
Description	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).
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

only data from participants with measures at both time points are included

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	57	55
Mean (Standard Deviation) [units on a scale]	0.6 (4.9)	1.7 (6.9)

4. Secondary Outcome

Title	Average Percent Adherence to Vitamin D Interventio
Description	adherence measured with pill counts for the vitamin D at predesignated study timepoints: baseline (after run-in), 3 months and 6 months
Time Frame	average for all study ppts for: screening to baseline; baseline to 3 months; 3 month to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	57	56
Number [% of adherence for each treatment arm]	95	95

5. Secondary Outcome

Title	Serum Estradiol Concentrations
Time Frame	baseline and 6 months

Outcome Measure Data

Analysis Population Description

only participants whose serum was obtained at both time points are included

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	52	50
Baseline	2.83 (0.1)	2.77 (0.1)
6 months	2.94 (0.16)	3.0 (0.12)

6. Secondary Outcome

Title	Change in Steady State Concentrations of Serum Anastrazole and Letrozole
Description	Difference in steady state concentrations in plasma from baseline to 6 months
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

Only study participants with baseline and 6 month blood samples available were analyzed

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	47	48
anastrozole	-1.31 (10.67)	2.4 (5.36)
letrozole	2.16 (9.69)	-0.83 (16.4)

7. Secondary Outcome

Title	Whole Body Bone Mineral Density
Description	GLM Mean and standard deviation of Whole Body Bone Mineral Density (grams/cm2) of Trial Participants by Treatment Arm after controlling for bisphosphonate use
Time Frame	From Baseline and 6 months of D3 supplementation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	53	54
Geometric Least Squares Mean (Standard Deviation) [gm/cm2]	1.1 (0.12)	1.12 (0.13)

8. Secondary Outcome

Title	Vitamin D Binding Protein Genotype
Time Frame	Baseline

Outcome Measure Data

Analysis Population Description

Due to funding limitations, this secondary aim was not collected and analyzed in these groups

Arm/Group Title	Vitamin D3 4000 IU	Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months	Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	Adverse events were collected with regard to the organ system
Arm/Group Title	Vitamin D3 4000 IU		Vitamin D3 600 IU
Arm/Group Description	Vitamin D3: Cholecalciferol capsule, 4000IU, daily for 6 months		Vitamin D3: cholecalciferol capsule, 600 IU, daily for 6 months
All Cause Mortality
	Vitamin D3 4000 IU		Vitamin D3 600 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vitamin D3 4000 IU		Vitamin D3 600 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/57 (0%)		0/56 (0%)
Other (Not Including Serious) Adverse Events
	Vitamin D3 4000 IU		Vitamin D3 600 IU
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	35/57 (61.4%)		32/56 (57.1%)
Cardiac disorders
Cardiac	2/57 (3.5%)		3/56 (5.4%)
Gastrointestinal disorders
Gastrointestinal complaints	12/57 (21.1%)		7/56 (12.5%)
General disorders
General	3/57 (5.3%)		1/56 (1.8%)
Injury, poisoning and procedural complications
Injuries	3/57 (5.3%)		4/56 (7.1%)
Metabolism and nutrition disorders
Metabolism and nutrition disorders	5/57 (8.8%)		3/56 (5.4%)
Musculoskeletal and connective tissue disorders
Musculoskeletal	10/57 (17.5%)		10/56 (17.9%)
Nervous system disorders
Nervous system disorders	7/57 (12.3%)		3/56 (5.4%)
Reproductive system and breast disorders
Reproductive and breast issues	2/57 (3.5%)		5/56 (8.9%)
Respiratory, thoracic and mediastinal disorders
Respiratory	9/57 (15.8%)		3/56 (5.4%)
Skin and subcutaneous tissue disorders
Skin problems	5/57 (8.8%)		5/56 (8.9%)
Surgical and medical procedures
Surgical and medical procedures	4/57 (7%)		1/56 (1.8%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.