Clinical trial NCT02311790: Palmitoleic Isomer Study
Official title: Supplementation With Vegetable Oils Enriched in the Fatty Acids Trans-C16:1 or Cis-C16:1: Dose-response Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Insulin Sensitivity
Keywords: cis-C16:1n7 supplement
trans-C16:1n7 supplement
palmitoleic acid supplement
Lead sponsor: Tufts University
Sponsor class: OTHER
First posted: 2014-12-08
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: OTHER

Brief summary: 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: 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.

Eligibility criteria: 1. 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
2. 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).

Primary outcomes:
measure: Plasma phospholipid fatty acid profiles -
timeFrame: 18 weeks
Secondary outcomes:
measure: Plasma sphingolipid profiles -
timeFrame: 18 weeks
measure: CBC
timeFrame: 18 weeks
measure: Insulin
timeFrame: 18 weeks
measure: Clinical Chemistry Profile
timeFrame: 18 weeks
measure: HDL-cholesterol
timeFrame: 18 weeks
measure: glucose
timeFrame: 18 weeks
measure: albumin
timeFrame: 18 weeks
measure: ALP
timeFrame: 18 weeks
measure: SGPT
timeFrame: 18 weeks
measure: SGOT
timeFrame: 18 weeks
measure: blood urea nitrogen
timeFrame: 18 weeks
measure: creatine phosphokinase
timeFrame: 18 weeks
Other outcomes:
Locations:
city: Boston
country: United States
facility: Jean Mayer Human Nutrition Research Center on Aging
state: Massachusetts
Study officials:
affiliation: Tufts University/Jean Mayer Human Nutrition Research Center on Aging
name: Alice H Lichtenstein, D.Sc.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Huang NK, Matthan NR, Galluccio JM, Shi P, Lichtenstein AH, Mozaffarian D. Supplementation with Seabuckthorn Oil Augmented in 16:1n-7t Increases Serum Trans-Palmitoleic Acid in Metabolically Healthy Adults: A Randomized Crossover Dose-Escalation Study. J Nutr. 2020 Jun 1;150(6):1388-1396. doi: 10.1093/jn/nxaa060.