Docosahexaenoic Acid (DHA) To Prevent Development of Cognitive Dysfunction Due to Chemotherapy

Study Overview
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Brief Summary
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The purpose of this study is to determine if a high dose of DHA begun prior to and continued during neo-adjuvant chemotherapy (chemotherapy given prior to surgery) is likely to prevent or lessen chemotherapy induced cognitive dysfunction.

Detailed Description
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Chemotherapy is often associated with problems of cognitive functioning such as decision making, learning, and memory. These symptoms, collectively referred to here as cognitive dysfunction can appear as early as the first few months after starting chemotherapy and may persist long after chemotherapy and anti-hormone therapy, if any, is completed. Once developed there is no satisfactory treatment for cognitive dysfunction although cognitive retraining and exercise may improve symptoms and/or function; at least for some. Omega-3 fatty acids derived from ocean fish are a new potential preventative treatment against development of cognitive problems which can arise in some individuals during chemotherapy treatment. In doses of 1-2 grams per day it has been found to improve some aspects of cognitive function in healthy adults who have low DHA dietary intake. It has also been shown to improve some aspects of function in individuals with a mild reduction in cognitive ability but not for those with marked impairment. Participation in this study will last about 12 months. Participants will make visits to the study site for both standard of care visits and additional study-related visits. Participants will be randomized (randomly assigned; like flipping a coin) to one of two groups. Neither the Investigator nor the participant will know the assigned treatment.

Official Title
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Docosahexaenoic Acid (DHA) To Prevent Development of Cognitive Dysfunction Due to Chemotherapy

Conditions
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Cognitive Dysfunction

Intervention / Treatment
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* Drug: DHA
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of invasive breast cancer (Stage I-III) and are anticipated to start neo-adjuvant chemotherapy (multiple chemotherapy regimens allowed under protocol) Able to read, write, and understand English and at least have a high school education. Able and willing to go at least 24-36 hours without narcotic pain medicine, muscle relaxants, sedatives, sleeping pills and alcohol prior to their cognitive testing. Participants should not have required chronic sedatives, sleeping aids, or narcotic pain medications on a daily basis prior to their diagnosis. Willing to complete required study procedures from start of study to approximately 6 months after completion of neo-adjuvant chemotherapy. Exclusion Criteria: Women who are currently on omega-3 fatty acid supplements with > 500 mg of EPA plus DHA daily or 250 mg of DHA alone and or who have chronically been on more than 1 fish oil capsule per day. Individuals who are not willing to stop fish or krill oil supplements during the study. Diabetics requiring insulin treatment. Individuals who are not likely to be able to go for 24 hours without sleeping pills, sedatives, narcotic pain medications, or ativan Individuals who do not have a high school education or are not fluent in English. Individuals who have already started chemotherapy for breast cancer or who have previously had systemic chemotherapy for a malignancy. Women who have already had definitive surgery for breast cancer.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: DHA<br>Participants will be asked to take four 400 mg (1600 mg; 1.6 grams) capsules of DHA daily. Participants will start taking capsules before the start of and for the duration of their neoadjuvant chemotherapy. | Drug: DHA<br>* 4 capsules of 400 mg DHA daily<br>* Other names: Docosahexaenoic Acid;|
| Placebo Comparator: Placebo<br>Participants will be asked to take four 400 mg (1600 mg; 1.6 grams) capsules of a matched placebo daily. Participants will start taking capsules before the start of and for the duration of their neoadjuvant chemotherapy. | Drug: Placebo<br>* Matched, blinded placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trial acceptance | Number of potentially eligible subjects who consent to participate in the study. | 12 months | 
| Subject retention and trial completion | Number of enrolled subjects who complete all cognitive assessments at all three defined timepoints. | Completion of study ( 12 months) | 
| Compliance with taking study agent. | Number of enrolled subjects who take at least 70% of prescribed study agent. | Completion of study ( 12 months) | 
| Number of subjects reporting serious adverse events | Number of enrolled subjects randomized to DHA who report serious adverse events (adjusted for subjects randomized to placebo who report serious adverse events). | Completion of study ( 12 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Cognitive Ability-General Concerns Questionnaire | Change measured using Patient-Reported Outcomes Measurement Information System (PROMIS-General Concerns). There are a total of 34 questions. Each question has five response options ranging in value from one to five (never to very often). The total score is based on the sum of the responses, multiplied by the number of questions and then divided by the number of questions that were answered. | Baseline to Month 12 | 
| Change in Cognitive Ability-Abilities Questionnaire | Change measured using Patient-Reported Outcomes Measurement Information System (PROMIS-Abilities). There are a total of 33 questions. Each question has five response options ranging in value from one to five (never to very often). The total score is based on the sum of the responses, multiplied by the number of questions and then divided by the number of questions that were answered. | Baseline to Month 12 | 
| Change in Quality of Life Questionnaire | Change measured using Patient-Reported Outcomes Measurement Information System (PROMIS 29-Profile). The PROMIS 29-Profile includes 4 items from 7 different domains (Depression, Anxiety, Physical Function, Pain Interference, Fatigue, Sleep Disturbance, and Ability to Participate in Social Roles and Activities, along with a single item on pain intensity). The total score is based on the sum of the responses, multiplied by the number of questions and then divided by the number of questions that were answered. | Baseline to Month 12 | 
| Level of Physical Activity Questionnaire | Physical activity will be tracked over course of the study. Participants will complete a physical activity questionnaire (PAQ-4) at each visit. | Month 12 | 
| Change in Cognitive Function test | Change measured based on standard battery of cognitive tests including Hopkins Verbal Learning Test-Revised, Trail Making A, Trail Making B and Controlled Oral Word Association. | Change from Baseline to Month 12 | 
| Measurement of Cognitive Function Mobile Cognitive Assessment Battery (MCAB) Questionnaire | The MCAB measures working memory, divided attention/multitasking, cognitive flexibility and processing speed and also includes a 33 item self-rating questionnaire that assesses everyday cognitive behaviors, physical activity, sleep, pain and functional adjustment. | Change from Baseline to Month 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DHA, Omega-3, neoadjuvant chemotherapy, chemotherapy, breast cancer