SPM Regulation by Fish Oil Supplements in Healthy Volunteers

NCT ID: NCT03347006

Last Updated: 2025-05-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-03-20
• Study Completion Date: 2018-06-15

Brief Summary

A randomised, double-blind, placebo-controlled study to determine whether fish oil supplementation regulates peripheral levels of specialized pro-resolving mediators and white blood cell responses in healthy volunteers

Detailed Description

Rationale for the study The relationship between omega-3 essential fatty acid supplementation, and specifically fish oil supplementation, and SPM production in humans is very poorly understood. Given that the body produces SPM from omega-3 essential fatty acids to regulate inflammation and also to repair damaged tissues, it is critical to gain further insights on how the body utilizes dietary supplementation of omega-3 fatty acids from fish oils for SPM formation. With the availability of a mass spectrometry based platform developed by the investigators the scientific community is now in a unique position to better understand the biology of fish oil supplementation by monitoring the levels of SPM in plasma. This understanding may in turn shed light into the beneficial actions of omega-3 supplementation. It may also provide new leads for the control of excessive inflammation, as found in chronic inflammatory disorders, via dietary supplementation to exploit the body's own defense systems.

Rationale for choice of doses Given that in a study using a different fish oil source and formulation the investigators found that 1 g of essential fatty acids gave a mild but significant increase in plasma SPM levels (25) the investigators chose the lowest dose in the study to be of 1.5g. with the other two doses being within the European Food Safety Authority's Tolerable Upper Intake Level for supplements containing both EPA and DHA. Given that this limit is of 5 g and previous study with both healthy volunteers and patients demonstrated that doses up to 4 g are well tolerated (22-24), the investigators chose the remaining 2 doses to be 3.0 g and 4.5 g. In addition, this supplement was awarded a Generally Recognized as Safe Status (see appendix 1) in the for a dose of up to 5 g. Similar doses of the emulsion from of the fish oil supplement are also being used in an ongoing clinical study in the USA (ClinicalTrials.gov Identifier: NCT02719665) measuring different outcomes to those being investigated in the present study.

Aim of research The aim of this research is to investigate whether fish oil supplementation increases the peripheral blood levels of SPM and whether fish oil supplementation also regulates peripheral white blood cell responses (including neutrophils, monocytes and platelets) to inflammatory stimuli.

Original hypothesis Given that fish oils are rich in omega-3 essential fatty acids that are precursors in the biosynthesis of SPM the hypothesis underlying the present study is: Fish oil supplementation increase peripheral blood levels of SPM precursors that may be converted to bioactive mediators which in turn will regulate white blood cell responses.

Conditions

Healthy Volunteers

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Placebo

Placebo control

Group Type: PLACEBO_COMPARATOR

SPM Active

Intervention Type: DIETARY_SUPPLEMENT

Supplement or placebo will be administered orally between 9 am to 9:30 am.

• Each participant will give a baseline blood sample then they will be given one of the randomly allocated three doses of fish oil supplement, or a matching placebo in one of 8 study groups [this will be on a 1:1:1:1:1:1:1:1 ratio]. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation/placebo, 12ml per time interval.

Dose 1

1.5 g of omega-3 supplement

Group Type: EXPERIMENTAL

SPM Active

Intervention Type: DIETARY_SUPPLEMENT

Supplement or placebo will be administered orally between 9 am to 9:30 am.

• Each participant will give a baseline blood sample then they will be given one of the randomly allocated three doses of fish oil supplement, or a matching placebo in one of 8 study groups [this will be on a 1:1:1:1:1:1:1:1 ratio]. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation/placebo, 12ml per time interval.

Dose 2

3.0 g of omega-3 supplement

Group Type: EXPERIMENTAL

SPM Active

Intervention Type: DIETARY_SUPPLEMENT

Supplement or placebo will be administered orally between 9 am to 9:30 am.

• Each participant will give a baseline blood sample then they will be given one of the randomly allocated three doses of fish oil supplement, or a matching placebo in one of 8 study groups [this will be on a 1:1:1:1:1:1:1:1 ratio]. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation/placebo, 12ml per time interval.

Dose 3

4.5 g of omega-3 supplement

Group Type: EXPERIMENTAL

SPM Active

Intervention Type: DIETARY_SUPPLEMENT

Supplement or placebo will be administered orally between 9 am to 9:30 am.

• Each participant will give a baseline blood sample then they will be given one of the randomly allocated three doses of fish oil supplement, or a matching placebo in one of 8 study groups [this will be on a 1:1:1:1:1:1:1:1 ratio]. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation/placebo, 12ml per time interval.

Interventions

SPM Active

Supplement or placebo will be administered orally between 9 am to 9:30 am.

• Each participant will give a baseline blood sample then they will be given one of the randomly allocated three doses of fish oil supplement, or a matching placebo in one of 8 study groups [this will be on a 1:1:1:1:1:1:1:1 ratio]. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation/placebo, 12ml per time interval.

Intervention Type: DIETARY_SUPPLEMENT

Eligibility Criteria

Inclusion Criteria

• For participants to be included in the study they will need to meet the following criteria:

1. Able to provide informed consent

2. Men and women between the age of 18 and 45

3. Declare not to be taking aspirin, other NSAIDS, other form of medication or omega-3 fatty acid supplements for more than 2 weeks prior to screening and the duration of the participation.

4. Willingness to abstain from eating fish for 2 days before each study visit

5. Willingness to abstain from alcohol consumption for at least 24h prior to each study visit

6. Willingness to abstain from caffeine as directed before and during study

Exclusion Criteria

• 1) History of, chronic disorders, cardiovascular disease (e.g., heart disease, stroke), cancer, or diabetes or significant genetically inherited conditions.

2) Pregnancy or breast-feeding. 3) Hypothyroidism in the opinion of the investigator. 4) Liver disease in the opinion of the investigator. 5) Any abnormality or pre-existing disease which, in the opinion of the investigator, might either expose the subject to risk, or influence the validity of the results.

6) Women of childbearing potential not taking adequate methods of contraception 7) Inability to read and write in English 8) Participation in a clinical study of a new chemical entity, biological product or a prescription medicine, or loss of more than 400 mL blood, within the previous 3 months 9) Anyone who is currently smoking or used to smoke 10) Presence or history of drug or alcohol abuse or intake of more than the amount of alcohol in the current guidelines on alcohol consumption

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Metagenics, Inc.

INDUSTRY

Sponsor Role: collaborator

Queen Mary University of London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Queen Mary University of London

London, , United Kingdom

Countries

United Kingdom

References

Souza PR, Marques RM, Gomez EA, Colas RA, De Matteis R, Zak A, Patel M, Collier DJ, Dalli J. Enriched Marine Oil Supplements Increase Peripheral Blood Specialized Pro-Resolving Mediators Concentrations and Reprogram Host Immune Responses: A Randomized Double-Blind Placebo-Controlled Study. Circ Res. 2020 Jan 3;126(1):75-90. doi: 10.1161/CIRCRESAHA.119.315506. Epub 2019 Dec 12.

Reference Type: DERIVED

PMID: 31829100 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

16/LO/2182

Identifier Type: OTHER

Identifier Source: secondary_id

011549

Identifier Type: -

Identifier Source: org_study_id