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| ID | Type | Description | Link |
|---|---|---|---|
| 16/LO/2182 | Other Identifier | Research ethics council |
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| Name | Class |
|---|---|
| Metagenics, Inc. | INDUSTRY |
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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Placebo control |
|
| Dose 1 | Experimental | 1.5 g of omega-3 supplement |
|
| Dose 2 | Experimental | 3.0 g of omega-3 supplement |
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| Dose 3 | Experimental | 4.5 g of omega-3 supplement |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| SPM Active | Dietary Supplement | Supplement or placebo will be administered orally between 9 am to 9:30 am.
|
| Measure | Description | Time Frame |
|---|---|---|
| Increase in the Average Peripheral Blood SPM Levels | The Primary endpoint of the study will be an increase in peripheral blood SPM levels that will be measured calculated by measuring pre-supplement SPM levels to values measured in plasma after supplementation. | outcomes will be measured 24h post supplementation and compared with baseline values (0h) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | Measure ability of peripheral blood neutrophils to uptake S. aureus following pre- and post- supplementation. Looking at relationship between amount of omega-3 fatty acids ingested, the increase in the blood levels of these molecules and white blood cell function. | Outcomes will be measured 24h post supplementation and compared with baseline values (at 0h) |
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Inclusion Criteria:
For participants to be included in the study they will need to meet the following criteria:
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
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Queen Mary University of London | London | EC1M 6BQ | United Kingdom |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 31829100 | Derived | 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. |
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| ID | Title | Description |
|---|---|---|
| FG000 | Group 1 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered a placebo. Blood will be collected again at 2h, 4h, 6h and 24h after placebo administration, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 1.5g of supplement and blood collected at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 3 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 4.5 g of marine oils and blood drawn 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. |
| FG001 | Group 2 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered a 1.5g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 3 g of supplement and blood collected at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 4.5 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given placebo and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG002 | Group 3 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered a 3 g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 4.5 g of supplement and blood collected at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a placebo and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 1.5 g of marine oils and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG003 | Group 4 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered a 4.5 g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered placebo and blood collected at 2h, 4h, 6h and 24h later, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 1.5 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 3 g of marine oils and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG004 | Group 5 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered 4.5 g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 3g of marine oils and blood collected at 2h, 4h, 6h and 24h later, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 1.5 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given placebo and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG005 | Group 6 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered 3 g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 1.5 g of marine oils and blood collected at 2h, 4h, 6h and 24h later, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a placebo and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 4.5 g of marine oils and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG006 | Group 7 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered 1.5 g of marine oils. Blood will be collected again at 2h, 4h, 6h and 24h after supplementation, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered placebo and blood collected at 2h, 4h, 6h and 24h later, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 4.5 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 3 g of marine oils and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| FG007 | Group 8 | Participants will be assigned randomly to this group. They give a baseline blood sample then they will be administered placebo. Blood will be collected again at 2h, 4h, 6h and 24h later, 12ml per time interval. After a minimum interval of 48 hours from the last blood draw, participants will give blood, they will be administered 4.5 g of marine oils and blood collected at 2h, 4h, 6h and 24h later, 12ml per time interval. Participants will be asked to return after a minimum of 48 hours from the last blood draw and blood (baseline) will be collected. The participants will be administered a 3 g of marine oils and blood collected after 2h, 4h, 6h and 24h, 12ml per time interval. After a minimum of 48h from the last blood draw participants will donate blood, they will be then given 1.5 g of marine oils and blood drawn 2h, 4h, 6h and 24h, 12ml per time interval. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Study Population | Since this is a crossover study all the participants in this study will recieved all the study interventions ie 1.5g, 3g 4.5g of marine oils and placebo. These will be administered in one of 8 sequences which will be determined by assigning the volunteer to one of 8 study groups. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | This was a cross over study to every participant received each of the treatments |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Increase in the Average Peripheral Blood SPM Levels | The Primary endpoint of the study will be an increase in peripheral blood SPM levels that will be measured calculated by measuring pre-supplement SPM levels to values measured in plasma after supplementation. | healthy volunteers | Posted | Mean | Standard Deviation | pg/mL | outcomes will be measured 24h post supplementation and compared with baseline values (0h) |
|
Up to 1 month after the last supplement/placebo dose was administered, an average of 40 days
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | Placebo control SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Professor Jesmond Dalli | Queen Mary University of London | +442078828263 | j.dalli@qmul.ac.uk |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 19, 2016 | Oct 13, 2022 | Prot_SAP_000.pdf |
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SPM Active is the supplement tested in this study
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Double blind placebo controlled
|
| Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | Changes in the expression of protein linked with neutrophil activation, determined by comparing expression levels of this protein in peripheral blood cells pre- and post supplementation. | outcomes measured 24h post supplementation and compared with baseline values (at 0h) |
| Count of Participants |
| Participants |
|
| Age, Continuous | Study had a cross over design so all participants received all treatments | This was a cross over study | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Study was a cross over study so all participants received all treatments | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Study had a cross over design so all participants received all treatments | Study had a cross over design so all participants received all treatments | Number | participants |
|
| Height | Study had a cross over design so all participants received all treatments | Study had a cross over design so all participants received all treatments | Mean | Standard Deviation | meters |
|
| Weight | Study had a cross over design so all participants received all treatments | Study had a cross over design so all participants received all treatments | Mean | Standard Deviation | Kg |
|
| body mass index | Study had a cross over design so all participants received all treatments | Study had a cross over design so all participants received all treatments | Mean | Standard Deviation | kg/m2 |
|
| Systolic Blood Pressure | Mean | Standard Deviation | mmHg |
|
| Pulse | Mean | Standard Deviation | bpm |
|
| Sodium | Mean | Standard Deviation | mmol/L |
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| Potassium | Mean | Standard Deviation | mmol/L |
|
| Chloride ions | Mean | Standard Deviation | mmol/L |
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| Urea | Mean | Standard Deviation | mmol/L |
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| Creatinine | Mean | Standard Deviation | umol/L) |
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| Protein | Mean | Standard Deviation | g/L |
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| Albumin (g/L) | Mean | Standard Deviation | g/L |
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| Bilirubin | Mean | Standard Deviation | µmol/L |
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| adenosine triphosphate | Mean | Standard Deviation | U/L |
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| Alanine aminotransferase | Mean | Standard Deviation | U/L |
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| Aspartate Transferase | Mean | Standard Deviation | U/L |
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| Calcium | Mean | Standard Deviation | mml/L |
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| Phosphate (mmol/L) | Mean | Standard Deviation | mmol/L |
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| Urate | Mean | Standard Deviation | µmol/L |
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| estimated glomerular filtration rate | Mean | Standard Deviation | ml/min/1.73m^2 |
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| Cholesterol | Mean | Standard Deviation | mmol/L |
|
| Triglycerides | Mean | Standard Deviation | mmol/L |
|
| High density lipoprotein | Mean | Standard Deviation | mmol/L |
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| Low density lipoprotein | Mean | Standard Deviation | mmol/L |
|
| Cholesterol -HDL ratio | Mean | Standard Deviation | ratio |
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| non-HDL Cholesterol | Mean | Standard Deviation | mmol/L |
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| White blood cell count | Mean | Standard Deviation | cells*10^6/L |
|
| platelet counts | Mean | Standard Deviation | cells 10^9 /L |
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| Hematocrit | Mean | Standard Deviation | L/L |
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| Red blood cell count | Mean | Standard Deviation | cells 10^12/L |
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| OG001 | Dose 1 | 1.5 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
|
| OG002 | Dose 2 | 3.0 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
|
| OG003 | Dose 3 | 4.5 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
|
|
|
| Secondary | Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | Measure ability of peripheral blood neutrophils to uptake S. aureus following pre- and post- supplementation. Looking at relationship between amount of omega-3 fatty acids ingested, the increase in the blood levels of these molecules and white blood cell function. | Posted | Mean | Standard Error | percent change from baseline | Outcomes will be measured 24h post supplementation and compared with baseline values (at 0h) |
|
|
|
| Secondary | Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | Changes in the expression of protein linked with neutrophil activation, determined by comparing expression levels of this protein in peripheral blood cells pre- and post supplementation. | Posted | Mean | Standard Error | percent change from baseline values | outcomes measured 24h post supplementation and compared with baseline values (at 0h) |
|
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|
| 0 |
| 22 |
| 0 |
| 22 |
| 0 |
| 22 |
| EG001 | Dose 1 | 1.5 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
| 0 | 22 | 0 | 22 | 0 | 22 |
| EG002 | Dose 2 | 3.0 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
| 0 | 22 | 0 | 22 | 0 | 22 |
| EG003 | Dose 3 | 4.5 g of omega-3 supplement SPM Active: Supplement or placebo will be administered orally between 9 am to 9:30 am.
| 0 | 22 | 0 | 22 | 0 | 22 |
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