Clinical trial NCT03625427: Effect of Palmitoleic Acid on C-reactive Protein
Official title: Effects of Palmitoleic Acid on Circulating C-reactive Protein Levels in Humans
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Chronic Inflammation
Overweight
Keywords: palmitoleic acid
monounsaturated fatty acid
chronic inflammation
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: Organic Technologies
First posted: 2018-08-10
Enrollment: 123
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. 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
2. Generally healthy adults
3. Understand protocol and comply to take supplements during the trial
4. Ability to understand English
5. Be able to report to clinical research center, fasting, at least 3 times
6. Women who are of childbearing potential should be on birth control (one method is acceptable)

Exclusion Criteria:

1. BMI higher than 40.0
2. Taking anti-hyperlipidemia medications (including statins)
3. Taking anti-diabetic medications
4. Auto-immune disease
5. Documented cognitive impairment
6. Unable to draw blood from veins
7. Alcohol or other drug dependency
8. Are currently breastfeeding, or pregnant, or plan to become pregnant
9. Have experienced a significant weight change of 10%, or more, of body weight in previous 3 months
10. If on hormone therapy, no change during study
11. Chronic use of NSAIDs
12. Decreased QOL due to pathology, such as cancer, genetic diseases, Rx side effects, or injury
13. Taking fish oil, within 8 weeks of enrollment
14. Taking Seabuckthorn supplements
15. Taking sterols or fat blockers
16. Fish allergies

Primary outcomes:
measure: Mean c-reactive protein circulating level
timeFrame: Week 12
Secondary outcomes:
measure: Mean circulating cytokine IL-6 level
timeFrame: Week 12
measure: Mean circulating cytokine TNF alpha level
timeFrame: Week 12
measure: Mean circulating ghrelin level
timeFrame: Week 12
measure: Mean circulating peptide YY level
timeFrame: Week 12
measure: Mean circulating leptin level
timeFrame: Week 12
measure: Mean circulating adiponectin level
timeFrame: Week 12
measure: Mean glucose/insulin ratio level
timeFrame: Week 12
measure: Mean HbA1c level
timeFrame: Week 12
Other outcomes:
Locations:
city: Kannapolis
country: United States
facility: University of North Carolina Nutrition Research Institute
state: North Carolina
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Saame R Shaikh, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Frigolet ME, Gutierrez-Aguilar R. The Role of the Novel Lipokine Palmitoleic Acid in Health and Disease. Adv Nutr. 2017 Jan 17;8(1):173S-181S. doi: 10.3945/an.115.011130. Print 2017 Jan.
citation: Yadav A, Kataria MA, Saini V, Yadav A. Role of leptin and adiponectin in insulin resistance. Clin Chim Acta. 2013 Feb 18;417:80-4. doi: 10.1016/j.cca.2012.12.007. Epub 2012 Dec 22.
citation: Schirmer M, Smeekens SP, Vlamakis H, Jaeger M, Oosting M, Franzosa EA, Ter Horst R, Jansen T, Jacobs L, Bonder MJ, Kurilshikov A, Fu J, Joosten LAB, Zhernakova A, Huttenhower C, Wijmenga C, Netea MG, Xavier RJ. Linking the Human Gut Microbiome to Inflammatory Cytokine Production Capacity. Cell. 2016 Nov 3;167(4):1125-1136.e8. doi: 10.1016/j.cell.2016.10.020.
citation: de Souza CO, Vannice GK, Rosa Neto JC, Calder PC. Is Palmitoleic Acid a Plausible Nonpharmacological Strategy to Prevent or Control Chronic Metabolic and Inflammatory Disorders? Mol Nutr Food Res. 2018 Jan;62(1). doi: 10.1002/mnfr.201700504. Epub 2017 Dec 11.
citation: Bernstein AM, Roizen MF, Martinez L. WITHDRWAN: Purified palmitoleic acid for the reduction of high-sensitivity C-reactive protein and serum lipids: a double-blinded, randomized, placebo controlled study. J Clin Lipidol. 2014 Nov-Dec;8(6):612-617. doi: 10.1016/j.jacl.2014.08.001. Epub 2014 Aug 19.