Palmitoleic Isomer Study

Study Overview
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Brief Summary
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Trans-palmitoleic acid (trans-C16:1) is a naturally occurring trans fatty acid present in small quantities in foods, most notably in dairy products. Observational evidence suggests a positive association between trans-C16:1 and insulin sensitivity, and negative association with risk of developing type 2 diabetes mellitus [1-3]. Cis-palmitoleic acid (cis-C16:1) is found naturally in foods and is particularly high in macadamia nuts and oil extracted from the sea buckthorn plant. Animal models suggest that this palmitoleic acid isomer also improves insulin sensitivity and reduces metabolic dysfunction. This pilot dosing study is necessary to inform the design of a larger trial to test the hypothesis that both trans-C16:1 and cis-C16:1 improve insulin resistance but at different doses. Plasma phospholipid fatty acid profiles will be used as the primary outcome measure.

Detailed Description
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The fatty acids trans-C16:1 and cis-C16:1 have been associated with healthy plasma glucose levels. Elevated glucose levels have been associated with diabetes. This study is designed to determine whether there is a dose-response relation between how much trans-C16:1 and cis-C16:1 you consume and how much appears in plasma. This information will be used to design a future study to determine whether trans-C16:1 and cis-C16:1 could be used to treat diabetes. Trans-C16:1 occurs naturally in dairy fat such as milk and cheese, while cis-C16:1 occurs naturally in nuts, particularly, macadamia nuts, and a plant called sea buckthorn. The study will consist of two 9-week phases, with a minimum of a 4 week off-study period between the two phases. Fasting blood will be drawn at baseline (first day of week 1), 3 weeks, 6 weeks and 9 weeks (4 total blood draws per phase or 8 total blood draws for 2 phases). During each phase you will be asked to consume increasing numbers of vegetable oil capsules, 2 per day during the first 3 weeks, 4 per day during the second 3 weeks, and 8 per day during the third 3 weeks. During each of these periods you should take half the capsules in the morning and half in the evening, with your meals. You will be randomly assigned to receive the trans-C16:1 or cis-C16:1 during the first phase and the other during the second phase. The total length of the study is about 18 weeks, not including the break between phase 1 and phase 2 (not less than 4 weeks). The trans-C16:1 in the capsules will be in the form of partially-hydrogenated soybean oil. The cis-C16:1 in the other capsules will be in the form of sea buckthorn oil.

Official Title
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Supplementation With Vegetable Oils Enriched in the Fatty Acids Trans-C16:1 or Cis-C16:1: Dose-response Study

Conditions
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Insulin Sensitivity

Intervention / Treatment
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* Dietary Supplement: Trans-C16:1 supplement
* Dietary Supplement: Cis-C16:1 supplement


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Age ≥ 18 to ≤ 70 years BMI ≥ 25 kg/m2 ≤ 40 kg/m2 Normotensive with or without medication Normal fasting plasma glucose levels (≤120 mg/dL) Normal kidney function as assessed by serum creatinine and blood urea nitrogen Normal liver function as assessed by serum glutamic pyruvic transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT) and alkaline phosphatase (ALP) Normal thyroid function defined as screening TSH within normal ranges, without or with medication for at least 6 months Normal gastrointestinal function Exclusion criteria: Use of supplements containing fish oil or other lipid supplements (e.g., flaxseed, primrose oil, sea buckthorn oil) within 3 months of study participation Greater than 2 servings/day combined of cheese, whole-fat milk or whole-fat yogurt Diagnosed diabetes mellitus Type I or Type II and/or taking glucose lowering medications (e.g., metformin, actos, januvia) Use of medication known to affect lipid metabolism (HMG-CoA reductase inhibitors (statins, red yeast rice), bile acid sequestrants, cholesterol absorption inhibitors (exetimibe [Zetia]), nicotinic acid agents, fibrates, probucol, anticoagulants, hormone therapy medications containing estrogen, anabolic steroids) Established major chronic diseases such as major cardiovascular disease (history of myocardial infarction, stroke, symptomatic heart failure, coronary artery bypass graft, or symptomatic peripheral arterial disease), active cancer, end stage renal disease, dementia, severe chronic obstructive pulmonary disease, significant liver disease Pregnancy or breastfeeding Unwillingness to adhere to study protocol No Social Security number (for payment and IRS forms).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Other
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Trans-C16:1 supplement<br>Volunteers will take trans-C16:1 supplement for 3 weeks | Dietary Supplement: Trans-C16:1 supplement<br>* Each volunteer will consume 3 escalating doses (120 mg/day, 240 mg/day and 480 mg/day) of trans-C16:1 enriched vegetable oil for 3 weeks each (3 doses x 3 weeks each [9 weeks total]<br>|
| Experimental: Cis-C16:1 supplement<br>Volunteers will take cis-C16:1 supplement for 3 weeks | Dietary Supplement: Cis-C16:1 supplement<br>* Each volunteer will consume 3 escalating doses (380 mg/day, 760 mg/day and 1520 mg/day) of cis-C16:1 enriched vegetable oil for 3 weeks each (3 doses x 3 weeks each [9 weeks total]<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma phospholipid fatty acid profiles - | PLP FA profile determined by gas chromatography | 18 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma sphingolipid profiles - | sphingolipid profile determined by qTOF (quadrupole time of flight mass spectrometry) | 18 weeks | 
| CBC | complete blood count | 18 weeks | 
| Insulin | determined by ELISA | 18 weeks | 
| Clinical Chemistry Profile | glucose, albumin, ALP, SGPT, SGOT, blood urea nitrogen, creatine phosphokinase, creatinine, lactate dehydrogenase, total protein, bilirubin, globulin, albumin/globulin ratio, uric acid, calcium, phosphorus, magnesium, sodium, potassium, chloride, total and LDL-cholesterol, triglyceride | 18 weeks | 
| HDL-cholesterol | automated immunoturbidimetric assay | 18 weeks | 
| glucose | part of chemistry panel | 18 weeks | 
| albumin | part of chemistry panel | 18 weeks | 
| ALP | alkaline phosphatase - part of chemistry panel | 18 weeks | 
| SGPT | serum glutamic pyruvic transaminase - part of chemistry panel | 18 weeks | 
| SGOT | serum glutamic oxaloacetic transaminase - part of chemistry panel | 18 weeks | 
| blood urea nitrogen | assessment of kidney function - part of chemistry panel | 18 weeks | 
| creatine phosphokinase | muscle enzymes - part of chemistry panel | 18 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cis-C16:1n7 supplement, trans-C16:1n7 supplement, palmitoleic acid supplement