Bioavailability of SPMs in Obese Humans

Not Applicable

Completed

• Conditions: Obesity Adult Onset
• Interventions: Dietary Supplement: SPM Active

• Registration Number: NCT04701138
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief 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).

Study Timeline

• Study First Submitted: 2021-01-05
• Study First Submitted QC: 2021-01-05
• Study First Posted: 2021-01-08
• Study Start: 2021-02-04
• Primary Completion: 2021-06-02
• Study Completion: 2021-06-18
• Status Verified: 2022-03
• Results First Submitted: 2022-03-10
• Results First Submitted QC: 2022-06-14
• Last Update Submitted: 2022-06-14
• Results First Posted: 2022-06-15
• Last Update Posted: 2022-06-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

• 24 (n=12 male + 12 female) obese (BMI 30-40 kg/m^2) subjects with age 50-65 years who are euglycemic and pre-diabetic (i.e. fasting glucose 70-125 mg/dL or HbA1c of 5.7-6.4%).
• Only post-menopausal females will be recruited in the female cohort to reduce the confounding effects of estrogen on lipid metabolism during supplementation.

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Exclusion Criteria

• Those with fasting glucose values > 126 mg/dL or known type 2 diabetes
• Females who are pre-menopausal, pregnant, planning to become pregnant, breastfeeding or lactating
• Subjects consuming n-3 PUFA supplements in the last 3 months prior to enrollment, high consumption of fatty fish (>2 servings per week), and subjects with active autoimmune disease, liver disease, coagulopathy, hypothyroidism, known allergy to fish or shellfish, inability to give informed consent, or taking anticoagulants (e.g. warfarin and direct-acting anticoagulants), those taking estrogen or testosterone, and anyone taking daily aspirin, NSAIDs, or active asthma medications.
• Subjects receiving immunomodulatory or immunosuppressant therapy (corticosteroids or monoclonal antibodies) in the 4 weeks prior to study enrollment, and subjects with known active malignancy or undergoing treatment for malignancy will be excluded.
• Subjects who test positive for COVID-19 or have tested positive in the past will be excluded. Those who report COVID-19 or flu-like symptoms will be excluded, as well as those that fail to pass COVID-19 screening at baseline.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Dietary Supplement	SPM Active	All subjects will receive the intervention (SPM Active Supplement)

Primary Outcome Measures

Name	Time	Method
Mean Pro-inflammatory & Pro-resolving Metabolites	From Baseline (Week 1/Day1) through 28 to 30 days of supplementation	Mass spectrometry metabololipidomics analysis will be performed on plasma samples from pre/post supplementation blood draws to measure SPM concentrations. The study was powered to measure the following molecules of interest: 14-HDHA, 17-HDHA, and 18-HEPE.

Secondary Outcome Measures

Name	Time	Method
Mean White Blood Cell Populations	From Baseline (Week 1/Day1) through 28 to 30 days of supplementation	Immunological phenotyping of blood peripheral mononuclear cells (PBMC) using flow cytometry will identify key immune cell populations pre/post supplementation. PBMC analyses represent B cell populations, monocyte populations, natural killer cell populations, and T cell populations. The relative abundance was calculated using two different flow cytometry panels with fluorescently labeled antibodies. The first panel measured the relative abundance of all B cell subsets, monocyte subsets, and NK cell subsets (i.e., all subsets within error add up to 1.0). The second panel measured the relative abundance of CD4 T cell subsets, CD8 T cell subsets, and NKT cells (i.e., all subsets within error add up to 1.0).

Trial Locations

Locations (1)

UNC Chapel Hill Family Medicine Center; 🇺🇸 Chapel Hill, North Carolina, United States