Omega-3 Fatty Acids in Preventing Joint Symptoms in Patients With Stage I-III Breast Cancer Receiving Anastrozole, Exemestane, or Letrozole

Not Applicable

Completed

• Conditions: Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage II Breast Cancer; Stage IA Breast Cancer; Recurrent Breast Cancer; Stage IB Breast Cancer; Stage IIIA Breast Cancer
• Interventions: Other: Placebo; Dietary Supplement: omega-3 fatty acid supplement; Other: Clinical assessments; Other: Assessment of therapy complications; Procedure: Magnetic Resonance Imaging; Procedure: Correlative/special studies

• Registration Number: NCT01478477
• Lead Sponsor: Ohio State University Comprehensive Cancer Center

Brief Summary

This randomized pilot trial studies omega-3 fatty acid in preventing joint symptoms in patients with stage I-III breast cancer receiving anastrozole, exemestane, or letrozole. Omega-3 fatty acid supplement may lessen or prevent joint stiffness or pain in patients receiving hormone therapy for breast cancer.

Detailed Description

OBJECTIVES:

I. To assess the feasibility of evaluating joint symptoms in postmenopausal women with breast cancer randomized to n-3 PUFA (omega-3 fatty acid) vs. placebo supplementation using the Functional Assessment of Cancer Therapy-Breast (FACT-B) and endocrine subscale (FACT-ES), Brief Pain Inventory (BPI) and Stanford's Health Assessment -Disability Index (HAS) during the first 6 months of adjuvant aromatase inhibitor (AI) therapy.

II. To preliminarily evaluate the efficacy of n-3 PUFA vs. placebo supplementation on AI induced joint symptoms.

III. To explore blood and imaging based biomarkers (plasma and red blood cell \[RBC\] levels of n-3 PUFAs, inflammatory cytokines and receptors, and intra-articular tenosynovial inflammation by musculoskeletal magnetic resonance imaging \[MRI\] imaging) of AI-induced joint symptoms in women on AI therapy randomized to n-3 PUFAs vs. placebo supplementation.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive omega-3 fatty acid orally (PO) once daily (QD) for 6 months in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive placebo PO QD for 6 months in the absence of disease progression or unacceptable toxicity.

Study Timeline

• Study Start: 2011-10-04
• Study First Submitted: 2011-11-14
• Study First Submitted QC: 2011-11-21
• Study First Posted: 2011-11-23
• Primary Completion: 2014-01-09
• Study Completion: 2014-01-09
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-24
• Last Update Posted: 2023-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 44

Inclusion Criteria

• Women diagnosed with breast cancer stages I-III initiating first adjuvant AI therapy with any of the Food and Drug Administration- (FDA) approved AIs (anastrozole, 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
• History of osteoarthritis and/or fibromyalgia 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, with the exception of osteoarthritis and fibromyalgia
• AI use > 2 weeks prior to study enrollment
• Known bleeding disorders
• History of diabetes mellitus, heart disease or TIA/stroke
• 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 regular or any other supplements that might interact with n-3 PUFA supplements within six months of study initiation; sporadic use of n-3 PUFA supplement may be eligible if there has been a 3-month washout period prior to randomization
• Pregnant or nursing women
• Known sensitivity or allergy to fish or fish oil
• Concurrent use of daily full dose aspirin (≥ 325 mg/day), nonsteroidal anti-inflammatory drugs (NSAIDs) or NSAID-containing products or steroids; one month washout period is required prior to randomization
• Unable to give informed consent
• In patients consenting for optional MRIs, any contraindication to MRI examination including but not limited to ferromagnetic metal in the body, pacemaker, or severe claustrophobia

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (omega-3 fatty acid supplement)	Clinical assessments	Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Arm I (omega-3 fatty acid supplement)	Correlative/special studies	Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Arm II (placebo)	Placebo	Typical American Diet oils (TAD)
Arm II (placebo)	Assessment of therapy complications	Typical American Diet oils (TAD)
Arm II (placebo)	Magnetic Resonance Imaging	Typical American Diet oils (TAD)
Arm II (placebo)	Correlative/special studies	Typical American Diet oils (TAD)
Clinical Assessments	omega-3 fatty acid supplement	Brief Pain Inventory (BPI), Stanford's Health Assessment-Disability Index (HAS), FACT-B and endocrine subscale (FACT-ES)
Correlative/special studies	Placebo	Enrolled participants will have peripheral blood samples drawn for plasma and RBC n-3 PUFA levels within 4 weeks of starting AI therapy.
Arm I (omega-3 fatty acid supplement)	omega-3 fatty acid supplement	Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Arm I (omega-3 fatty acid supplement)	Magnetic Resonance Imaging	Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Assessment of therapy complications	omega-3 fatty acid supplement	Adverse events will be monitored by self-reporting of signs and symptoms. Patients will maintain a daily diary of time of supplement intake and any possible ill effects, with instructions to contact the PI or Research Nurse to discuss and manage any possible side effects.
Arm I (omega-3 fatty acid supplement)	Assessment of therapy complications	Omega 3 Polyunsaturated Fatty Acids(n-3 PUFA)
Clinical Assessments	Placebo	Brief Pain Inventory (BPI), Stanford's Health Assessment-Disability Index (HAS), FACT-B and endocrine subscale (FACT-ES)
Magnetic Resonance Imaging	omega-3 fatty acid supplement	Optional bilateral hand and wrist MRI imaging will be obtained
Magnetic Resonance Imaging	Placebo	Optional bilateral hand and wrist MRI imaging will be obtained
Arm II (placebo)	Clinical assessments	Typical American Diet oils (TAD)
Assessment of therapy complications	Placebo	Adverse events will be monitored by self-reporting of signs and symptoms. Patients will maintain a daily diary of time of supplement intake and any possible ill effects, with instructions to contact the PI or Research Nurse to discuss and manage any possible side effects.
Correlative/special studies	omega-3 fatty acid supplement	Enrolled participants will have peripheral blood samples drawn for plasma and RBC n-3 PUFA levels within 4 weeks of starting AI therapy.

Primary Outcome Measures

Name	Time	Method
Pain score change after 6 months (6 months -baseline) based on the FACT-B/ES instrument	baseline, 6 months	Pain scores based on FACT-B/ES, HAS and BPI will be plotted over time for each arm. Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.

Secondary Outcome Measures

Name	Time	Method
Pain score change after 6 months (6 months -baseline) based on the HAS and BPI instruments	baseline, 6 months	Agreement between HAS, BPI-short and FACT-B/ES evaluated using Altman and Bland plot after proper data transformation. Also, Linear Mixed model used to explore if the pain scores are different at 3 and 6 months. Logistic regression models used to compare the occurrence of moderate to severe joint symptoms during the 6 month period between the two treatment groups, with potential covariates including age, body mass index, baseline pain scores (0 month), prior chemotherapy and other variables.
Compliance rates with oral supplements (omega-3 fatty acid and placebo)	baseline, 6 months
Feasibility of using the instruments HAS, BPI-short, FACT-B/ES for the assessment of joint symptoms	baseline, 6 months
Effectiveness of blinding	baseline, 6 months	Summarized using a Chi-square test.
Relationship between serum and RBC omega-3 fatty acid levels, inflammatory blood markers and MRI changes and the joint symptoms	baseline, 6 months	Scatter plots and correlation coefficients (either Pearson or Spearman) will be used to summarize their pair wise relation. The differences between the treatment and placebo in terms of these measures will also be reported using numerical summaries and graphic plots.
Correlation of guess with pain scores	baseline, 6 months	Checked using logistic models to see if treatment guesses are explained by the patient's awareness of clinical benefit.

Trial Locations

Locations (1)

Ohio State University Medical Center; 🇺🇸 Columbus, Ohio, United States