- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04701138
Bioavailability of SPMs in Obese Humans
Bioavailability of Specialized Pro-resolving Mediators in Obese Humans
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.
Study Overview
Status
Conditions
Intervention / Treatment
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 Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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North Carolina
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Chapel Hill, North Carolina, United States, 27514
- UNC Chapel Hill Family Medicine Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dietary Supplement
All subjects will receive the intervention (SPM Active Supplement)
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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.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean Pro-inflammatory & Pro-resolving Metabolites
Time Frame: From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
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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.
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From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Mean White Blood Cell Populations
Time Frame: 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).
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From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
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Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Antibody Concentrations in Culture
Time Frame: From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
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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.
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From Baseline (Week 1/Day1) through 28 to 30 days of supplementation
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Collaborators and Investigators
Investigators
- Principal Investigator: Saame R Shaikh, PhD, University of North Carolina, Chapel Hill
- Study Director: Erik Butler, DO, UNC Family Medicine
Publications and helpful links
General Publications
- Crouch MJ, Kosaraju R, Guesdon W, Armstrong M, Reisdorph N, Jain R, Fenton J, Shaikh SR. Frontline Science: A reduction in DHA-derived mediators in male obesity contributes toward defects in select B cell subsets and circulating antibody. J Leukoc Biol. 2019 Aug;106(2):241-257. doi: 10.1002/JLB.3HI1017-405RR. Epub 2018 Dec 21.
- Kosaraju R, Guesdon W, Crouch MJ, Teague HL, Sullivan EM, Karlsson EA, Schultz-Cherry S, Gowdy K, Bridges LC, Reese LR, Neufer PD, Armstrong M, Reisdorph N, Milner JJ, Beck M, Shaikh SR. B Cell Activity Is Impaired in Human and Mouse Obesity and Is Responsive to an Essential Fatty Acid upon Murine Influenza Infection. J Immunol. 2017 Jun 15;198(12):4738-4752. doi: 10.4049/jimmunol.1601031. Epub 2017 May 12.
- Serhan CN, Levy BD. Resolvins in inflammation: emergence of the pro-resolving superfamily of mediators. J Clin Invest. 2018 Jul 2;128(7):2657-2669. doi: 10.1172/JCI97943. Epub 2018 May 14.
- Lopez-Vicario C, Titos E, Walker ME, Alcaraz-Quiles J, Casulleras M, Duran-Guell M, Flores-Costa R, Perez-Romero N, Forne M, Dalli J, Claria J. Leukocytes from obese individuals exhibit an impaired SPM signature. FASEB J. 2019 Jun;33(6):7072-7083. doi: 10.1096/fj.201802587R. Epub 2019 Mar 6.
- Al-Shaer AE, Regan J, Buddenbaum N, Tharwani S, Drawdy C, Behee M, Sergin S, Fenton JI, Maddipati KR, Kane S, Butler E, Shaikh SR. Enriched Marine Oil Supplement Increases Specific Plasma Specialized Pro-Resolving Mediators in Adults with Obesity. J Nutr. 2022 Jul 6;152(7):1783-1791. doi: 10.1093/jn/nxac075.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- 20-0131
- 550KR242033 (Other Grant/Funding Number: NC TraCS)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Informed Consent Form (ICF)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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