Omega-3 Supplementation in Prevention of Aromatase Inhibitor-Induced Toxicity in Patients With Stage I-III Breast Cancer

Sponsor

Ohio State University Comprehensive Cancer Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT02831582

Collaborator

National Cancer Institute (NCI) (NIH)

120

Enrollment

Locations

Arms

62.6

Anticipated Duration (Months)

Patients Per Site

0.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This clinical trial studies the use of omega-3 fatty acid supplementation in preventing aromatase inhibitor-induced toxicity in patients with stage I-III breast cancer. An omega-3 supplementation may help relieve moderate to severe bone pain and improve joint symptoms caused by aromatase inhibitor-induced arthralgias.

Condition or Disease	Intervention/Treatment	Phase
Arthralgia Breast Neoplasms	Dietary Supplement: Omega-3 Fatty Acid Other: Placebo	N/A

Detailed Description

PRIMARY OBJECTIVES:

To determine the efficacy of the complementary therapy omega-3 fatty acid (n-3 PUFA) supplementation in preventing aromatase inhibitor-induced arthralgias (AIIAs).

SECONDARY OBJECTIVES:

To prospectively define the population most at risk for developing AIIAs by the identification and validation of genetic risk predictors and to develop a single nucleotide polymorphism (SNP)/gene profile predictive of treatment intervention response.

OUTLINE: Patients are randomized to 1 of 2 groups.

Group I: Patients receive omega-3 fatty acid supplementation orally (PO) once daily (QD) for 6 months.

Group II: Patients receive placebo PO QD for 6 months.

After completion of study, patients will be followed up periodically.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Supportive Care

Official Title:

Prevention of Aromatase Inhibitor-Induced Toxicity With Omega-3 Supplementation

Actual Study Start Date :

Oct 12, 2016

Anticipated Primary Completion Date :

Jul 31, 2021

Anticipated Study Completion Date :

Dec 31, 2021

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Arm I (omega-3 fatty acid) Patients receive omega-3 fatty acid supplementation PO QD for 6 months.	Dietary Supplement: Omega-3 Fatty Acid Given PO. Other Names: n-3 Fatty Acid Omega 3 Fatty Acid OMEGA-3 FATTY ACIDS Omega-3 Polyunsaturated Fatty Acid Omega-3 PUFA omega-3-Fatty Acids
Placebo Comparator: Arm II (placebo) Patients receive placebo PO QD for 6 months.	Other: Placebo Given PO. Other Names: placebo therapy sham therapy

Arm

Intervention/Treatment

Active Comparator: Arm I (omega-3 fatty acid)

Patients receive omega-3 fatty acid supplementation PO QD for 6 months.

Dietary Supplement: Omega-3 Fatty Acid

Given PO.

Other Names:

n-3 Fatty Acid

Omega 3 Fatty Acid

OMEGA-3 FATTY ACIDS

Omega-3 Polyunsaturated Fatty Acid

Omega-3 PUFA

omega-3-Fatty Acids

Placebo Comparator: Arm II (placebo)

Patients receive placebo PO QD for 6 months.

Other: Placebo

Given PO.

Other Names:

placebo therapy

sham therapy

Outcome Measures

Primary Outcome Measures

Change in pain score based on the Brief Pain Inventory (BPI) [Baseline to up to 6 months]
Analysis of patterns of change over time in pain scores through the application of hierarchical linear regression models.

Secondary Outcome Measures

Change in joint symptoms based on quality of life instruments [Baseline to up to 6 months]
An exploratory analysis, logistic mixed effect regression models will be used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups.
Change in joint symptoms based on symptomatology instruments [Baseline to up to 6 months]
An exploratory analysis, logistic mixed effect regression models will be used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups.
Identification and validation of genetic risk predictors for aromatase inhibitor-induced arthralgias [Up to 6 months]
Interaction tests between treatment and stratification variables will be conducted to explore whether these factors are predictive of average pain scores.
Rate of compliance [Up to 6 months]
The rates of adherence to and discontinuation of AI therapy will be recorded. Reasons for treatment discontinuation will be described. In addition, the investigators will also examine the compliance rates with n-3 PUFA or placebo supplements with pill counts at each visit and with a patient recorded medication calendar.
SNP analysis by standard data preprocessing operations and sequential analysis [Up to 6 months]
A sequential analysis of the data that allows filtering of extraneous SNPs and select SNP loci, identification and creation of predictive SNP clusters, and then evaluation of the networks' potential clinical and biological validity will be performed.

Other Outcome Measures

Level of inflammatory markers [Up to 6 months]
Red blood cells (RBC) n-3 PUFA levels [Up to 6 months]
The relationship between RBC n-3 PUFA levels, inflammatory blood markers and the joint symptoms evaluated by the patient symptom assessment instruments. Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pairwise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Women diagnosed with breast cancer stages I-III initiating first line adjuvant aromatase inhibitor (AI) therapy with any of the FDA-approved AIs (anastrazole, exemestane, letrozole)
Concurrent gonadotropin-releasing hormone (GnRH) agonist therapy is allowed; concurrent breast related radiation therapy is allowed.
Prior tamoxifen use is allowed
Prior chemotherapy is allowed
Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

Metastatic malignancy of any kind
Rheumatoid arthritis and other types of autoimmune and inflammatory joint disease
AI use > 21 days prior to study enrollment
Known bleeding disorders
Current use of warfarin or other anticoagulants
Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situation that would limit compliance with study requirements
Daily use of n-3 PUFA concentrates or capsules or any other supplements that might interact with n-3 PUFA supplements if > 375 mg per day of of eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) within six months of study initiation
Pregnant or nursing women
Known sensitivity or allergy to fish or fish oil
Unable to give informed consent

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	City of Hope	Duarte	California	United States	91010
2	Cleveland Clinic Cancer Center/Fairview Hospital	Cleveland	Ohio	United States	44195
3	Ohio State University Comprehensive Cancer Center	Columbus	Ohio	United States	43210