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

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

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.

Study Overview

• Status: Completed
• Conditions: Breast Neoplasms; Arthralgia
• Intervention / Treatment: Dietary supplement: Omega-3 Fatty Acid; Other: Placebo

Detailed Description

PRIMARY OBJECTIVES:

I. 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:

I. 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 Type: Interventional
• Enrollment (Actual): 75
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • Duarte, California, United States, 91010
      • City of Hope
  • Ohio
    • Cleveland, Ohio, United States, 44195
      • Cleveland Clinic Cancer Center/Fairview Hospital
    • Columbus, Ohio, United States, 43210
      • Ohio State University Comprehensive Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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: Omega 3 Fatty Acid; Omega-3 PUFA; n-3 Fatty Acid; OMEGA-3 FATTY ACIDS; Omega-3 Polyunsaturated Fatty Acid; 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

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in joint symptoms based on quality of life instruments	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.	Baseline to up to 6 months
Change in joint symptoms based on symptomatology instruments	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.	Baseline to up to 6 months
Identification and validation of genetic risk predictors for aromatase inhibitor-induced arthralgias	Interaction tests between treatment and stratification variables will be conducted to explore whether these factors are predictive of average pain scores.	Up to 6 months
Rate of compliance	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.	Up to 6 months
SNP analysis by standard data preprocessing operations and sequential analysis	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.	Up to 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Level of inflammatory markers		Up to 6 months
Red blood cells (RBC) n-3 PUFA levels	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.	Up to 6 months

Collaborators and Investigators

• Sponsor: Ohio State University Comprehensive Cancer Center
• Collaborators: National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Roberts KE, Adsett IT, Rickett K, Conroy SM, Chatfield MD, Woodward NE. Systemic therapies for preventing or treating aromatase inhibitor-induced musculoskeletal symptoms in early breast cancer. Cochrane Database Syst Rev. 2022 Jan 10;1(1):CD013167. doi: 10.1002/14651858.CD013167.pub2.

Helpful Links

• The Jamesline

Study record dates

Study Major Dates

• Study Start (Actual): October 12, 2016
• Primary Completion (Actual): December 11, 2021
• Study Completion (Actual): December 11, 2021

Study Registration Dates

• First Submitted: May 1, 2016
• First Submitted That Met QC Criteria: July 8, 2016
• First Posted (Estimate): July 13, 2016

Study Record Updates

• Last Update Posted (Estimate): February 27, 2023
• Last Update Submitted That Met QC Criteria: February 24, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Breast Cancer; Postmenopausal; Stage IA; Stage IB; Stage IIA; Stage IIB; Stage IIIA; Stage IIIB; Stage IIIC
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Pain; Neurologic Manifestations; Breast Diseases; Joint Diseases; Musculoskeletal Diseases; Breast Neoplasms; Arthralgia
• Other Study ID Numbers: OSU-15222; NCI-2016-00377 (Registry Identifier: CTRP (Clinical Trial Reporting Program))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No