Trial Outcomes & Findings for Altering Lipids for Tolerance of Aromatase Inhibitor Therapy (NCT NCT04268134)

Last Updated: 2026-05-06

Results Overview

Plasma oxylipins from blood samples collected at the start of O3-FA supplementation (3 months after start of Aromatase Inhibitor \[AI\] therapy alone) and after 3 months of AI therapy + O3-FA supplementation (6 months after start of AI therapy alone) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (linoleic acid \[LA\], arachidonic acid \[AA\], alpha-linoleic acid \[ALA\], eicosapentaenoid acid \[EPA\], and docosahexaenoic acid \[DHA\]). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group. The results reported are the change in mean results.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

77 participants

Primary outcome timeframe

From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy)

Results posted on

2026-05-06

Participant Flow

7 patients were enrolled but did not start study treatment

Participant milestones

Participant milestones
Measure	Omega 3 Fatty Acid Supplement Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Overall Study STARTED	70
Overall Study COMPLETED	50
Overall Study NOT COMPLETED	20

Reasons for withdrawal

Reasons for withdrawal
Measure	Omega 3 Fatty Acid Supplement Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Overall Study Adverse Event	3
Overall Study noncompliance	2
Overall Study Withdrawal by Subject	10
Overall Study Physician Decision	5

Baseline Characteristics

Altering Lipids for Tolerance of Aromatase Inhibitor Therapy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Age, Categorical <=18 years	0 Participants n=54 Participants
Age, Categorical Between 18 and 65 years	45 Participants n=54 Participants
Age, Categorical >=65 years	25 Participants n=54 Participants
Sex: Female, Male Female	70 Participants n=54 Participants
Sex: Female, Male Male	0 Participants n=54 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=54 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	69 Participants n=54 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=54 Participants
Race (NIH/OMB) American Indian or Alaska Native	1 Participants n=54 Participants
Race (NIH/OMB) Asian	1 Participants n=54 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=54 Participants
Race (NIH/OMB) Black or African American	4 Participants n=54 Participants
Race (NIH/OMB) White	63 Participants n=54 Participants
Race (NIH/OMB) More than one race	0 Participants n=54 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=54 Participants
Region of Enrollment United States	70 participants n=54 Participants

PRIMARY outcome

Timeframe: From start of Omega-3 Fatty Acid (O3-FA) supplementation to 3 months of O3-FA (at 6 months after start of AI therapy)

Population: The results reported are the change in the previously calculated, but not reported, at the start of the study and at 3 months. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA EPA	6.71 Change percentage of total fatty acids Standard Deviation 7.11
Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA DHA	2.17 Change percentage of total fatty acids Standard Deviation 2.61
Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA ALA	0.56 Change percentage of total fatty acids Standard Deviation 2.25
Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA AA	0.62 Change percentage of total fatty acids Standard Deviation 1.96
Change in Percentage of Total Fatty Acids for Each Polyunsaturated Fatty Acid (PUFA) Group From Start of Omega-3 Fatty Acid (O3-FA) Supplementation to 3 Months of O3-FA LA	7.51 Change percentage of total fatty acids Standard Deviation 50.82

SECONDARY outcome

Timeframe: At 6 months after start of AI therapy

Plasma oxylipins from blood samples collected at baseline (before AI therapy) and at 3 months of AI therapy + O3-FA supplementation (O3-FA supplementation starts 3 months after start of AI therapy) will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 6 Months of Aromatase Inhibitor (AI) (3 Months of AI Alone + 3 Months of AI With O3-FA Supplementation) EPA	6.77 percentage of total fatty acids Standard Deviation 12.10
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 6 Months of Aromatase Inhibitor (AI) (3 Months of AI Alone + 3 Months of AI With O3-FA Supplementation) DHA	1.78 percentage of total fatty acids Standard Deviation 5.44
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 6 Months of Aromatase Inhibitor (AI) (3 Months of AI Alone + 3 Months of AI With O3-FA Supplementation) ALA	0.31 percentage of total fatty acids Standard Deviation 3.03
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 6 Months of Aromatase Inhibitor (AI) (3 Months of AI Alone + 3 Months of AI With O3-FA Supplementation) AA	0.27 percentage of total fatty acids Standard Deviation 1.74
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 6 Months of Aromatase Inhibitor (AI) (3 Months of AI Alone + 3 Months of AI With O3-FA Supplementation) LA	1.02 percentage of total fatty acids Standard Deviation 5.01

SECONDARY outcome

Timeframe: At 3 months after start of AI therapy

Plasma oxylipins from blood samples collected at baseline and at 3 months after start of AI therapy alone will be quantified using solid phase extraction-liquid chromatography-electrospray ionization tandem mass spectroscopy. Oxylipins will be grouped according to PUFA substrate (LA, AA, ALA, EPA and DHA). For each patient, the percentage of total fatty acids of each PUFA group will be calculated at both time points. The overall study percentage per PUFA group will be derived from the mean percentage of that PUFA group for all patients at each time point. The change in percentage between the two time points will be reported in tabular format for each PUFA group.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 3 Months of AI Therapy Alone EPA	0.29 change percentage of total fatty acids Standard Deviation 1.48
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 3 Months of AI Therapy Alone DHA	0.03 change percentage of total fatty acids Standard Deviation 1.47
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 3 Months of AI Therapy Alone ALA	0.04 change percentage of total fatty acids Standard Deviation 1.04
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 3 Months of AI Therapy Alone AA	0.10 change percentage of total fatty acids Standard Deviation 1.54
Change in Percentage of Total Fatty Acids for Each PUFA Group From Baseline to 3 Months of AI Therapy Alone LA	1.26 change percentage of total fatty acids Standard Deviation 7.04

SECONDARY outcome

Timeframe: Up to 9 months after start of AI therapy

Patients will be considered to have developed AIMSS if any of the following apply: (1) a ≥0.22 increase in the Health Assessment Questionnaire (HAQ) score within 9 months, (2) a ≥2.0 increase in Brief Pain Inventory (BPI) average pain within 9 months, or (3) discontinuation of AI therapy within 9 months because of new or worsened musculoskeletal symptoms, assessed using a protocol-specific discontinuation form completed by the patient's provider. The HAQ assesses interference of pain with daily activities (range 0-3), with change of 0.22 defined as a clinically meaningful difference, as noted in the literature.\* The BPI assesses average pain over 7 days (range 0-10), with a change of 2.0 defined as a clinically meaningful difference, as noted in the literature.\* Patients whose providers specify pain as the first or second-ranked reason for discontinuation will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms. \*See references.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Number of Participants Who Develop AI-associated Musculoskeletal Symptoms (AIMSS)	27 Participants

SECONDARY outcome

Timeframe: Up to 9 months after start of AI therapy

Patients whose providers specify pain as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy because of new or worsened musculoskeletal symptoms.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Number of Participants That Discontinue AI Therapy Due to AIMSS	16 Participants

SECONDARY outcome

Timeframe: Up to 9 months after start of AI therapy

Patients whose providers specify toxicity as the first or second-ranked reason for discontinuation (in a protocol-specific discontinuation form) will be considered to have discontinued AI therapy due to toxicity.

Outcome measures

Outcome measures
Measure	Omega 3 Fatty Acid Supplement n=70 Participants Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Number of Participants That Discontinue AI Therapy Due to Toxicity.	22 Participants

Adverse Events

Omega 3 Fatty Acid Supplement

Serious events: 1 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Omega 3 Fatty Acid Supplement n=70 participants at risk Omega-3 ethyl esters orally daily (containing 465 mg eicosapentaenoic acid \[EPA\] and 375 mg docosahexaenoic acid \[DHA\] per capsule,supplied as 4 x 1gm capsule) Omega-3 fatty acid supplement: 4 capsules taken by mouth each day for 24 weeks (starting at the week 12 visit).
Skin and subcutaneous tissue disorders Skin infection	1.4% 1/70 • Number of events 1 • All adverse event data (serious and non-serious) collected from the time of the initial study treatment administration through 30 days after the last dose of study treatment. Up to 7 months.

Other adverse events

Adverse event data not reported

Additional Information

University of Michigan Rogel Cancer Center ClinicalTrials.gov Admin

University of Michigan Rogel Cancer Center

Phone: 734-936-9499

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place