Obesity Adult Onset
Conditions
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).
Interventions
DIETARY_SUPPLEMENTSPM Active
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.
Sponsors
Metagenics, Inc.
North Carolina Translational and Clinical Sciences Institute
University of North Carolina, Chapel Hill
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
50 Years to 65 Years
Healthy volunteers
No
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.
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Antibody Concentrations in Culture | From Baseline (Week 1/Day1) through 28 to 30 days of supplementation | B cells isolated from collected blood samples will be cultured in-vitro and stimulated with an antigen & produced antibody concentrations will be measured via ELISA. This will be done for pre & post blood samples. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Dietary Supplement All subjects will receive the intervention (SPM Active Supplement)
SPM Active: 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. | 23 |
| Total | 23 |
Baseline characteristics
| Characteristic | Dietary Supplement |
|---|---|
| Age, Continuous | 56 years |
| Body Mass Index (BMI) | 33.1 Kg/m^2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 23 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Height | 170.2 cm |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants |
| Race (NIH/OMB) Black or African American | 5 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 16 Participants |
| Region of Enrollment United States | 23 Participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 10 Participants |
| Weight | 96.4 Kg |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 24 |
| other Total, other adverse events | 0 / 24 |
| serious Total, serious adverse events | 0 / 24 |
Outcome results
Primary
Mean Pro-inflammatory & Pro-resolving Metabolites
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.
Time frame: From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Post 18-HEPE | 11.3 ng/mL | Standard Deviation 10.3 |
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Pre 14-HDHA | 15.6 ng/mL | Standard Deviation 11.5 |
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Post 14-HDHA | 12.2 ng/mL | Standard Deviation 5.4 |
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Pre 17-HDHA | 6.6 ng/mL | Standard Deviation 4.9 |
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Post 17-HDHA | 8.1 ng/mL | Standard Deviation 4.6 |
| Dietary Supplement | Mean Pro-inflammatory & Pro-resolving Metabolites | Pre 18-HEPE | 8.0 ng/mL | Standard Deviation 6.2 |
Secondary
Mean White Blood Cell Populations
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).
Time frame: From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dietary Supplement | Mean White Blood Cell Populations | Pre NK CD3-CD56HICD16+ | 0.01 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre CD4+ T Cells | 0.32 Relative abundance | Standard Deviation 0.07 |
| Dietary Supplement | Mean White Blood Cell Populations | Post CD4+ T Cells | 0.33 Relative abundance | Standard Deviation 0.05 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Activated CD4+ T Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Activated CD4+ T Cells | 0.03 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Non-Activated CD4+ T Cells | 0.30 Relative abundance | Standard Deviation 0.07 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Non-Activated CD4+ T Cells | 0.30 Relative abundance | Standard Deviation 0.05 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre CD8 T Cells | 0.17 Relative abundance | Standard Deviation 0.07 |
| Dietary Supplement | Mean White Blood Cell Populations | Post CD8 T Cells | 0.16 Relative abundance | Standard Deviation 0.05 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Activated CD8 T Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Activated CD8 T Cells | 0.03 Relative abundance | Standard Deviation 0.02 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Non-Activated CD8 T Cells | 0.15 Relative abundance | Standard Deviation 0.06 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Non-Activated CD8 T Cells | 0.13 Relative abundance | Standard Deviation 0.03 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre NKT Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NKT Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre B Cells | 0.39 Relative abundance | Standard Deviation 0.08 |
| Dietary Supplement | Mean White Blood Cell Populations | Post B Cells | 0.37 Relative abundance | Standard Deviation 0.11 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Plasma Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Plasma Cells | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Follicular B Cells | 0.01 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre NK CD3-CD56dimCD16+ | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Follicular B Cells | 0.01 Relative abundance | Standard Deviation 0 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre B Regs | 0.08 Relative abundance | Standard Deviation 0.04 |
| Dietary Supplement | Mean White Blood Cell Populations | Post B Regs | 0.07 Relative abundance | Standard Deviation 0.04 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Classical Monocytes | 0.06 Relative abundance | Standard Deviation 0.02 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Classical Monocytes | 0.06 Relative abundance | Standard Deviation 0.03 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Intermediate Monocytes | 0.00 Relative abundance | Standard Deviation 0 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Intermediate Monocytes | 0.01 Relative abundance | Standard Deviation 0 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre Non-Classical Monocytes | 0.11 Relative abundance | Standard Deviation 0.06 |
| Dietary Supplement | Mean White Blood Cell Populations | Post Non-Classical Monocytes | 0.10 Relative abundance | Standard Deviation 0.07 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre NK CD3-CD56HICD16- | 0.01 Relative abundance | Standard Deviation 0 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NK CD3-CD56HICD16- | 0.02 Relative abundance | Standard Deviation 0.03 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NK CD3-CD56HICD16+ | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre NK CD3-CD56dimCD16- | 0.23 Relative abundance | Standard Deviation 0.09 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NK CD3-CD56dimCD16- | 0.22 Relative abundance | Standard Deviation 0.08 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NK CD3-CD56dimCD16+ | 0.02 Relative abundance | Standard Deviation 0.01 |
| Dietary Supplement | Mean White Blood Cell Populations | Pre NK CD3-CD56-CD16+ | 0.05 Relative abundance | Standard Deviation 0.03 |
| Dietary Supplement | Mean White Blood Cell Populations | Post NK CD3-CD56-CD16+ | 0.08 Relative abundance | Standard Deviation 0.08 |
Other Pre-specified
Antibody Concentrations in Culture
B cells isolated from collected blood samples will be cultured in-vitro and stimulated with an antigen & produced antibody concentrations will be measured via ELISA. This will be done for pre & post blood samples.
Time frame: From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
Population: One participant's sample was removed from all B cell isolation and stimulation studies (ELISA data) due to PBMC cell death upon sample freezing.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Dietary Supplement | Antibody Concentrations in Culture | Pre IgM | 465801.89 ng/mL | Standard Deviation 217732.43 |
| Dietary Supplement | Antibody Concentrations in Culture | Post IgM | 457833.05 ng/mL | Standard Deviation 238874.79 |
| Dietary Supplement | Antibody Concentrations in Culture | Pre IgG | 1024891.3 ng/mL | Standard Deviation 394612.17 |
| Dietary Supplement | Antibody Concentrations in Culture | Post IgG | 789525.69 ng/mL | Standard Deviation 320595.08 |