Bioavailability of SPMs in Obese Humans

NCT04701138 | Completed Results

• 2 other identifiers: 20-0131550KR242033
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity Adult Onset

Outcome Measures

Primary Outcomes (1)

• 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.

  From Baseline (Week 1/Day1) through 28 to 30 days of supplementation

Secondary Outcomes (1)

• Mean White Blood Cell Populations

  From Baseline (Week 1/Day1) through 28 to 30 days of supplementation

Other Outcomes (1)

• Antibody Concentrations in Culture

  From Baseline (Week 1/Day1) through 28 to 30 days of supplementation

Study Arms (1)

Dietary Supplement

EXPERIMENTAL

All subjects will receive the intervention (SPM Active Supplement)

Dietary Supplement: SPM Active

Interventions

SPM Active DIETARY_SUPPLEMENT

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.

Dietary Supplement

Eligibility Criteria

• Age: 50 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• Metagenics, Inc.: collaborator
• North Carolina Translational and Clinical Sciences Institute: collaborator

Study Sites (1)

UNC Chapel Hill Family Medicine Center

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (5)

• 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.

  PMID: 30576001 BACKGROUND

• 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.

  PMID: 28500069 BACKGROUND

• 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.

  PMID: 29757195 BACKGROUND

• 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.

  PMID: 30840838 BACKGROUND

• 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.

  PMID: 35349683 DERIVED

Results Point of Contact

• Title: Saame Shaikh, PhD
• Organization: University of North Carolina at Chapel Hill

shaikhsa@email.unc.edu

919-843-4348

Study Officials

• Saame R Shaikh, PhD

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

• Erik Butler, DO

  UNC Family Medicine

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 5, 2021
• First Posted: January 8, 2021
• Study Start: February 4, 2021
• Primary Completion: June 2, 2021
• Study Completion: June 18, 2021
• Last Updated: June 15, 2022
• Results First Posted: June 15, 2022

Record last verified: 2022-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, ANALYTIC CODE
• Time Frame: Data will be available 24-36 months after the completion of the study. Data will be available permanently.
• Access Criteria: Flow cytometry data will be deposited into ImmPort (https://www.immport.org/home). The raw metabololipidomics data will be made available by depositing the results in http://www.metabolomicsworkbench.org/. Analytic code and statistical analysis plans will be deposited on github.com. The study protocol, statistical analysis plan, \& informed consent form will be made available on clinicaltrials.gov.

Locations

US (1)