Omega-3 and Vitamin D Supplementation in Breast Cancer Women

Study Overview
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Brief Summary
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Breast cancer (BC) is the most common malignant disease, which is fifth leading cause of cancer mortality worldwide. Poor nutritional status is one of the common physical symptoms found among cancer patients, in which it is caused by both cancer disease state and its oncology treatment regimens used. Cancer patients develop a tumor-associated malnutrition characterized by an insufficient supply of macro- and micronutrients and systemic chemotherapy treatment that could significantly affecting the nutritional status of these patients by its side effects associated with chemotherapy that may lead to many medical complications that often requires hospitalization and death. An adequate nutritional intervention can have a beneficial impact on the disease condition and also the progress of the disease, as an integral part of adjuvant therapy on cancer care. Numerous studies had shown that the use of EPA and DHA are safe (absence of cardiotoxic effects) and effective in reducing the common chemotherapy-related side effects, such as bone density loss, peripheral neuropathy and weight gain. The question remains arises to whether administration of both vitamin D and omega-3 fatty acids supplementations could be used as important nutritional strategy during the active oncology treatment in breast cancer patients. In Palestine, nutritional intervention strategies are poorly evaluated in the oncology setting especially among patients undergoing chemotherapy. Suitable and proper nutritional interventions among breast cancer patients during active oncology treatments could help to improve nutritional status, decrease mortality and improve quality of life among these subjects. Hence, the present study is formulated to assess the effect of combined omega-3 fatty acid and vitamin D supplementation on the nutritional status, quality of life and blood inflammatory markers among breast cancer women undergoing chemotherapy treatment in the Gaza Strip, Palestine.

Detailed Description
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An adequate nutritional intervention can have a beneficial impacts on the disease condition and also the progress of the disease, as an integral part of adjuvant therapy on cancer care. Numerous clinical and epidemiological studies had found that vitamin D deficiency is common nutritional disorder in BC patients and that significantly associated with a negative prognostic factor, in which some have reported a positive effect of combining vitamin D or its analogues as an adjuvant therapy, together with a variety of chemotherapeutic factors used during oncology treatments. Moreover, combination of vitamin D and omega-3 fatty acids may provide a new complementary treatment by decreasing inflammatory biomarkers and resistance to cancer treatment in patients with BC. The question remains whether vitamin D and omega-3 fatty acids co-supplementation would actually be useful after diagnosis of BC. So, the aim of this study is to investigate the effects of vitamin D and omega-3 fatty acids co-supplementation on inflammatory biomarkers, and nutritional status in patients with BC.

Official Title
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The Effects of Combined Omega-3 and Vitamin D Supplementation on Nutritional Status, Quality of Life and Inflammatory Markers Among the Breast Cancer Women in Gaza Strip

Conditions
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Breast Cancer Female

Intervention / Treatment
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* Dietary Supplement: Omega-3 FA
* Dietary Supplement: Vitamin D
* Combination Product: Combined Omega-3 and Vitamin D Supplementation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females who have been newly diagnosed with the breast cancer of stage I, II and III Patients with following clinical diagnosis of breast cancer such as lymph node positive +ve, hormonal receptor negative -ve and human epidermal growth factor receptor 2 (HER2) negative -ve Patient will receive her first chemotherapy treatment with Adriamycin + Cytoxan (AC) for a total of four cycle (each cycle will be carried-out every 3 weeks (21 days) Exclusion Criteria: Participants who had already undertaken her chemotherapy previously, and/or other oncology treatments such as hormonal or radiation oncology therapy Patients with recurrent breast cancer, patients with other chronic disease conditions such as renal disease and under dialysis, HIV, malabsorption disorder diseases, autoimmune diseases, diabetes, hypertension, hepatic, parathyroid, and gastrointestinal disorders. Patients who have reported any allergy condition to fish and/or fish products Pregnant women

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 64 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
Interventional Model Description: An open-label randomized clinical trial of breast cancer women that are undergoing chemotherapy treatment for total duration of 2 months (approximately 9 weeks in total), in which participants will be randomly selected and included in either one of these four (4) experimental groups (arms).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group (A)<br>Participants will be received daily omega-3 fatty acid (two capsules of 1000mg fish oil daily). Each soft gel capsule contains 300 mg of omega-3 fatty acids in the bioactive triglyceride (TG) and 180mg EPA and 120 mg DHA. (Omega3 complex, Jamieson Laboratories, Canada) | Dietary Supplement: Omega-3 FA<br>* Two capsules of 1000mg fish oil daily (Each soft gel capsule contains 180mg EPA and 120 mg DHA)<br>|
| Experimental: Group (B)<br>Participants will be received only vitamin D (one capsule of 50,000IU weekly). Each film coated tablet of vitamin D contains 50,000 IU Vitamin D3 (Cholecalciferol). (J-Dee, Jerusalem Pharmaceutical Company, West bank, Palestine). | Dietary Supplement: Vitamin D<br>* one capsule of vitamin D3 weekly (one D3 capsule contains 50,000 IU)<br>|
| Experimental: Group (C)<br>Participants will be received both omega-3 fatty acids capsules and vitamin D3 capsule. (one capsule of D3 50,000 IU weekly + two omega-3 fatty acids capsules daily (each capsule contains 300 mg of omega-3 fatty acids) | Combination Product: Combined Omega-3 and Vitamin D Supplementation<br>* Two capsules of 1000mg fish oil daily (Each soft gel capsule contains 180mg EPA and 120 mg DHA) and one capsule of vitamin D3 weekly (one D3 capsule contains 50,000 IU)<br>|
| No Intervention: Group (D)<br>Participants will not be received any supplements and just receive oncology treatment as an usual oncology patient. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Nutritional status, as assessed by Body Mass Index | Body weight in kilograms and height in meters will be combined to report BMI in kg/m^2 | Change from Baseline BMI at 2 months | 
| Change of body weight | Body weight will be measured in kilograms | Change from Baseline Weight in kg at 2 months | 
| Change of Muscle Mass Status | Muscle mass status will be assessed by calf circumference levels in cm. Higher values of calf circumference is indicative of greater lean mass. | Change from Baseline calf circumference in cm at 2 months | 
| Change of Nutritional Status Condition, as assessed by the Patient-Generated Subjective Global Assessment PG-SGA | The PG-SGA will be based four components such as questions related to body weight status (scored 0-5), food intake (score 0-4); symptoms affecting oral food intake (scored 0-23), and lastly questions on daily activities and function, in which the degree of malnutrition of patients will be classified as (A) well-nourished; (B) moderately malnourished; or (C) severely malnourished. | Change from Baseline Nutritional Status Condition in category of well-nourished, moderately malnourished or severely malnourished at 2 months | 
| Change of Total Scale and Single-item measures Scores derived from the Quality of life questionnaire (QLQ C-30) assessment | The EORTC Core Quality of Life questionnaire (EORTC QLQ-C30) assessment of 30 questions to measure cancer patients' physical, psychological and social functions. All of the scales and single-item measures range in score from 0 to 100. Higher score for the functioning scales and global health status denote a better level of functioning (i.e. a better state of the patient), while higher scores on the symptom and single-item scales indicate a higher level of symptoms (i.e. a worse state of the patient). | Change from Baseline total scales and single-item measures scores (0 to 100 scores) at 2 months | 
| Change of Blood inflammatory markers of blood TNF-α levels | Blood concentration of TNF-α levels will be measured in unit pg/mL. | Change from baseline TNF-α levels in pg/mL at 2 months | 
| Change of Blood inflammatory markers of blood CRP levels | Blood concentration of CRP levels will be measured in nmol/L | Change from baseline CRP levels in nmol/L at 2 months | 
| Change of Nutritional Status Assessed by body weight levels | Body weight will be measured in kilograms | Change from baseline weight in kg at 2 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of Dietary Energy Intakes | Habitual dietary nutrients intake will be assessed by mean energy intakes in kcal | Change from Baseline dietary energy intakes in kcal at 2 months | 
| Change of Dietary Fat Intakes | Habitual dietary nutrients intake will be assessed by mean fat intakes in grams | Change from Baseline dietary fat intakes in grams at 2 months | 
| Change of Dietary Protein Intakes | Habitual dietary protein intakes will be assessed by mean protein intakes in grams | Change from Baseline dietary Protein intakes in grams at 2 months | 
| Change of Dietary Vitamin D intakes | Habitual dietary nutrients intake will be assessed by mean vitamin D intakes in micrograms | Change from Baseline Dietary Vitamin D Intakes in microgram at 2 months | 
| Lifestyle physical activity status | A short form of the international physical activity questionnaire (IPAQ) will be used to assess the physical activity levels of the study participants, in which three different category groups of inactive, minimally active and active will be categorised. | Change from Baseline Physical Activity Status (inactive, minimally active or active physical activity status) at 2 months |