Effect of Palmitoleic Acid on C-reactive Protein

Study Overview
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Brief Summary
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This clinical trial will test the effects of an n-7 monounsaturated fatty acid known as palmitoleic acid (POA) on a chronic inflammation marker in overweight subjects. The study will enroll male and female subjects from healthy populations with high levels of the inflammatory marker c-reactive protein (CRP). Investigators will then determine over time if palmitoleic acid supplementation can lower circulating levels of c-reactive protein. Investigators will administer palmitoleic acid at two doses in addition to a placebo and conduct a double-blind parallel arm study. Circulating CRP will be the primary endpoint and secondary endpoints are Interleukin 6 (IL-6), Tumor necrosis factor (TNF) alpha, ghrelin, peptide tyrosine tyrosine (peptide YY), cardio lipid markers, glucose, insulin, leptin, adiponectin, and red blood cell (RBC) and serum fatty acids.

Detailed Description
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Palmitoleic acid (POA) is a monounsaturated fatty acid that has recently been shown to function as a lipokine and is present in the human diet and in blood serum. While there is emerging evidence that POA can positively impact beta cell proliferation, reduce lipogenesis, support endothelial function, and suppress cytokine production, POA remains to be poorly studied for its beneficial anti-inflammatory potential. The latest studies suggest that POA could attenuate inflammation in metabolically active tissues. Therefore, the objective of this study is to determine if administration of POA in 2 varying doses to overweight participants with biomarkers of chronic inflammation will lower circulating c-reactive protein (CRP) and cytokine levels, as well as improve metabolism by lowering levels of circulating leptin and raising expression of adiponectin. The rationale for focusing on overweight individuals is that they routinely have elevated c-reactive protein levels and are highly prone to have chronic inflammation. Investigators propose a 12-week randomized, double blinded study to assess changes in select inflammatory markers, ghrelin, peptide YY, cardiovascular lipids, fatty acid levels, and glucose sensitivity markers in volunteers consuming either the test agent, 500 mg or 1,000 mg POA per day, or an olive oil containing fatty acid (placebo). There are three arms to study and 41 individuals per arm, thus, a total of 123 subjects. Approximately 30% loss of subjects is expected. Administration of the POA supplements and placebo (olive oil capsules) will be double blinded. The study sponsor will hold the code for the subjects and will randomize the capsules. Only the study sponsor will have the code. The identity of the capsules will be revealed after the completion of the study. Subjects will bring back their bottles at each of the concurrent visits and the end of the study to assess compliance and to account for any missed doses of POA. The rationale for selecting olive oil as a placebo is that olive oil is routinely consumed by the public. Additionally, oleic acid (the active ingredient of olive oil) is the most prevalent fatty acid in human circulation, and olive oil is a routine placebo for fatty acid intervention studies. The olive oil will not be extra virgin olive oil that has several bioactive components. POA is virtually tasteless, thus participants should not be able to self-identify their regimen of either placebo or active test agent. The rationale for the experimental dose follows what is commercially available in POA products, which average 700 mg per day and generally range from 450 - 1000 mg per day regimens. The rationale for the 12-week time frame is to ensure uptake of POA into the target cells.

Official Title
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Effects of Palmitoleic Acid on Circulating C-reactive Protein Levels in Humans

Conditions
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Chronic Inflammation, Overweight

Intervention / Treatment
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* Dietary Supplement: Placebo
* Dietary Supplement: Palmitoleic acid, 500 mg (Dose 1)
* Dietary Supplement: Palmitoleic acid, 1,000 mg (Dose 2)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subject will be free-living, middle-aged to older men and women between ages 18-80 years with BMIs between 20.0-40.0, and CRP greater than or equal to 2.0 mg/L Generally healthy adults Understand protocol and comply to take supplements during the trial Ability to understand English Be able to report to clinical research center, fasting, at least 3 times Women who are of childbearing potential should be on birth control (one method is acceptable) Exclusion Criteria: BMI higher than 40.0 Taking anti-hyperlipidemia medications (including statins) Taking anti-diabetic medications Auto-immune disease Documented cognitive impairment Unable to draw blood from veins Alcohol or other drug dependency Are currently breastfeeding, or pregnant, or plan to become pregnant Have experienced a significant weight change of 10%, or more, of body weight in previous 3 months If on hormone therapy, no change during study Chronic use of NSAIDs Decreased QOL due to pathology, such as cancer, genetic diseases, Rx side effects, or injury Taking fish oil, within 8 weeks of enrollment Taking Seabuckthorn supplements Taking sterols or fat blockers Fish allergies

Ages Eligible for Study
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Minimum Age: 18 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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: 12-week randomized, double blinded study in volunteers consuming either the test agent, 500 mg or 1,000 mg POA per day, or an olive oil containing fatty acid (placebo). There are three arms to study and 41 individuals per arm, thus, a total of 123 subjects.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>The placebo is olive oil, stripped of polyphenols, 70% oleic acid, and will be administered at two 1 gram capsules per day for twelve weeks. The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast. | Dietary Supplement: Placebo<br>* The placebo is olive oil, stripped of polyphenols, 70% oleic acid, administered as two 1-gram capsules per day. Packaged as single-serve packets containing 2 capsules for each daily dose.<br>* Other names: Olive oil;|
| Experimental: Palmitoleic acid, 500 mg (Dose 1)<br>POA Dose 1 is a 1 gram capsule containing 500 mg POA and one placebo capsule containing 500 mg olive oil per day for twelve weeks. The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast. | Dietary Supplement: Palmitoleic acid, 500 mg (Dose 1)<br>* Palmitoleic acid (POA) 1 gram capsules containing 500 mg POA<br>* Other names: POA;|
| Experimental: Palmitoleic acid, 1,000 mg (Dose 2)<br>POA Dose 2 is two, 1 gram capsules containing 500 mg POA, totaling 1,000 mg POA per day for twelve weeks.The doses will be administered in single serve packets containing two capsules for each daily dose to be taken at breakfast. | Dietary Supplement: Palmitoleic acid, 1,000 mg (Dose 2)<br>* Palmitoleic acid (POA) taken as two 1 gram capsules each containing 500 mg POA<br>* Other names: POA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean c-reactive protein circulating level | Fasting blood draws will be used to evaluate circulating CRP level by high-sensitivity c-reactive protein laboratory blood analysis. | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean circulating cytokine IL-6 level | Fasting blood draws will be used to evaluate circulating cytokine IL-6 level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean circulating cytokine TNF alpha level | Fasting blood draws will be used to evaluate circulating cytokine TNF alpha level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean circulating ghrelin level | Fasting blood draws will be used to evaluate circulating ghrelin level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean circulating peptide YY level | Fasting blood draws will be used to evaluate circulating peptide YY level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean circulating leptin level | Fasting blood draws will be used to evaluate circulating leptin level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean circulating adiponectin level | Fasting blood draws will be used to evaluate circulating adiponectin level by ELISA (enzyme-linked immunosorbent assay). | Week 12 | 
| Mean glucose/insulin ratio level | Fasting blood draws will be used to evaluate glucose/insulin ratio level. | Week 12 | 
| Mean HbA1c level | Fasting blood draws will be used to evaluate HbA1c level. | Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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palmitoleic acid, monounsaturated fatty acid, chronic inflammation