Bioavailability of SPMs in Obese Humans
Condition: Obesity Adult Onset
Study type: Interventional

Summary: 
      Research Question: Does 4 weeks of supplementation with 'SPM Active' lead to a statistically
      significant increase in plasma SPM concentration for obese human subjects? Primary Aim 1: To
      compare plasma SPM concentrations and immunological fitness pre- and post- oral SPM
      administration in the obese.

        -  Aim 1a: To quantify plasma SPM concentrations in plasma (pg/mL), serum (pg/mL) and PBMCs
           before and after 4 weeks of supplementation with 'SPM Active.' The concentration of SPMs
           in plasma, in addition to other PUFA-derived metabolites that share the same enzymatic
           pathways as SPMs, will be established at baseline and post-intervention using mass
           spectrometry-based metabololipidomics.

        -  Aim 1b: To measure in vitro antibody responses of B cells in PBMC pool with in vitro
           stimulation and cytokine production before and after 4 weeks of supplementation with
           'SPM Active.' In addition, researchers will quantify the relative abundance of differing
           immune cell populations.
    

Detailed description: 
      Purpose: Specialized pro-resolving mediators (SPMs) are a superfamily of lipid metabolites,
      predominantly derived from the n-3 polyunsaturated fatty acids (PUFAs) eicosapentaenoic (EPA)
      and docosahexaenoic acids (DHA). Previous research has established that obese mice and humans
      have lower circulating levels of SPMs relative to lean controls. In this study, SPMs will be
      administered as a dietary supplement to obese human subjects to establish: 1) their
      bioavailability in plasma, serum and peripheral blood mononuclear cells (PBMCs) and 2) their
      effects on immune cell abundance and in vitro antibody production. The rationale for focusing
      on immune cells is that SPMs may be targeting their abundance and phenotype. This study does
      not intend to make any health or health-related claims.

      Participants: A total of 24 (n=12 men + 12 women) obese (BMI 30-40 kg/m2) euglycemic and
      pre-diabetic subjects (fasting glucose 70-125 mg/dL or HbA1c of 5.7-6.4%) aged 50-65 years
      will be recruited by Dr. Erik Butler from the UNC Family Medicine Center in Chapel Hill.

      Procedures (methods): This is a non-randomized uncontrolled clinical trial. The study will
      provide the intervention 'SPM Active' provided by Metagenics. All subjects will be advised to
      take 4 capsules per day (2 capsules with breakfast and 2 capsules with dinner) of 'SPM
      Active' for 4 weeks total. Each capsule contains 145 mg of SPMs for a total daily dose of 580
      mg. Fasting blood will be drawn pre- and post-intervention using phlebotomy available under
      the direction of Dr. Butler. The scientific approach will rely on mass-spectrometry based
      metabololipidomics, immunophenotyping with flow cytometry, and anthropomorphic/blood
      pressure/BMI measurements (anthropometric measures are only intended for use in statistical
      analysis for confounding variables).
    

Intervention name(s): SPM Active
Intervention type(s): Dietary Supplement
Intervention description(s): Each capsule contains 145 mg of SPMs (fractionated marine lipids standardized to 18-HEPE, 14-HDHA, and 17-HDHA). All subjects will take 4 capsules orally each day for a total daily dose of 580 mg.
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Basic Science