Oxidative Stress and Nutritional Supplementation Intervention Study

Study Overview
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Brief Summary
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A major means whereby oxidative stress promotes aging-related disease is by activating inflammatory pathways. Decreasing oxidative stress and inflammation should ameliorate many of the problems associated with aging, including vascular dementia, Alzheimer's disease, osteoporosis, muscle wasting, insulin resistance, type 2 diabetes, and metabolic syndrome. Animal and human studies have demonstrated that consumption of vitamin D and phase 2 protein inducers decrease oxidative stress and associated inflammation. The flax lignan secoisolariciresinol diglucoside (SDG) is metabolized to enterolactone, a potent phase 2 protein inducer. Animal and human studies have shown that consumption of flax seed or its component SDG decreases hypertension, serum cholesterol, atherosclerosis, the growth of experimentally-induced cancers as well as metastases of human breast tumours implanted into nude mice, and delays the development of type 2 diabetes. Vitamin D plays a role in modulating inflammation, enhancing immunity (while suppressing autoimmune injury) and exerting control over cell differentiation. Adequate levels of vitamin D also appear to promote better glycemic control. The investigators predict that consumption of SDG in persons with adequate vitamin D status will decrease oxidative stress and associated inflammation. If this hypothesis is upheld, this research has the potential to greatly decrease healthcare costs while allowing healthier aging.

Official Title
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Community Alliance for Quality of Life in Long Term Care: Oxidative Stress and Nutritional Supplementation Intervention Study

Conditions
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Oxidative Stress, Inflammation, Aging, Dementia, Pain

Intervention / Treatment
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* Dietary Supplement: secoisolariciresinol diglucoside


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: adults residing in a long term care facility resident for a minimum of four weeks prior to entry able to comply with study protocol able to follow simple instructions able to give informed consent or has a legally acceptable representative who is able to provide consent Exclusion Criteria: Age below 60 or above 80 years. Individuals at risk of hypotension or with symptomatic hypotension. Fasting hypoglycemia. Unstable diabetes Diabetics taking insulin Current cancer or diagnosed with cancer in the past 2 years. Women with an immediate family history or personal history of breast cancer or ovarian cancer Significant liver disorder Significant gastrointestinal disorder including inflammatory bowel disease but not constipation Significant kidney disorder Unstable or severe cardiac disease, recent MI or stroke either in past 6 months or significantly (i.e., severely) affecting physical mobility. Unstable other medical disease including, but not limited to, pulmonary disorder, epilepsy and genitourinary disorder. Migraine with aura within the last year (as this is a risk factor for stroke). Current diagnosis of a bleeding condition, or at risk of bleeding. Significant immunocompromise. Other unstable conditions. Current use of hormone replacement therapy except thyroid medication Current use of warfarin, clopidogrel, ticlopidine, dipyridamole or their analogues. Intolerances or allergies to flax or vitamin D. Estimated probability of longevity of less than one year based on medical opinion

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: secoisolariciresinol diglucoside<br>Secoisolariciresinol diglucoside (SDG) supplementation as 0.8g/day of BeneFlax containing 300 mg SDG. 1000 IU vitamin D as standard of care. | Dietary Supplement: secoisolariciresinol diglucoside<br>* SDG supplementation as a packet of 0.8g/day of BeneFlax containing 300 mg SDG for 24 weeks<br>* Other names: Vitamin D NPN 80003663 WN Pharmaceuticals;|
| Placebo Comparator: Placebo<br>An equal volume of measured whey protein (unflavored) to the Beneflax and 1000 IU vitamin D as standard of care. | Dietary Supplement: secoisolariciresinol diglucoside<br>* SDG supplementation as a packet of 0.8g/day of BeneFlax containing 300 mg SDG for 24 weeks<br>* Other names: Vitamin D NPN 80003663 WN Pharmaceuticals;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of consumption of 300 mg/day of the flax lignan secoisolariciresinol diglucoside (SDG) in older adults (60-80 y) | Adverse event occurrences will be compared descriptively between the SDG and placebo groups. Safety will be assessed at 0, 6, 12, 18 and 24 weeks; as part of the blood collection (urea, creatinine, total bilirubin, platelets, hematocrit, haemoglobin, mean corpuscular haemoglobin, mean corpuscular volume, white blood cell count, total protein including albumin and prealbumin, total calcium, electrolytes, glucose, liver enzymes (AST, ALT, ALP), total protein, albumin, lipids, HbA1c (for diabetic participants). Blood pressure measurements will be performed every two weeks | 24 weeks | 
| Effect of SDG on oxidative stress and inflammation | SDG and placebo groups will be compared at 0, 12 and 24 weeks for changes in oxidative stress measurements (plasma malondialdehyde), pro-inflammatory markers (IL-6, IL-1α, IL-1β, 8-isoprostane, TNF-α, C-reactive protein). | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of SDG on quality of life | SDG and placebo groups will be compared at 0, 12 and 24 weeks for changes in cognitive function, pain, and physical function including falls, as well as performance of activities of daily living. | 24 weeks | 
| Effect of SDG supplement on blood levels of flax lignan metabolites | To further understand the pharmacology of SDG, we will analyze plasma levels of the SDG metabolites secoisolariciresinol, enterolactone and enterodiol in those subjects given flax lignan supplement. Levels will be determined 0, 12 and 24 weeks. | 24 weeks | 
| To measure effects of SDG on bone resorption | SDG and placebo groups will be compared at 0 and 24 weeks for changes in bone resorption as assessed by measurement of cross-linked N-telopeptides type I collagen serum levels. | 24 weeks | 
| Effect of SDG on blood lipids | SDG and placebo groups will be compared at 0, 12 and 24 weeks for changes in nonfasting levels of cholesterol, LDL, HDL, and triglycerides. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long term care, lignans, oxidative stress, inflammation, aging, dementia, postural balance, depression, muscle weakness, quality of life, pain