Healthy Volunteers
Conditions
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.
Interventions
DIETARY_SUPPLEMENTSPM 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.
Sponsors
Metagenics, Inc.
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Investigator)
Masking description
Double blind placebo controlled
Intervention model description
SPM Active is the supplement tested in this study
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Increase in the Average Peripheral Blood SPM Levels | outcomes will be measured 24h post supplementation and compared with baseline values (0h) | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | Outcomes will be measured 24h post supplementation and compared with baseline values (at 0h) | 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. |
| Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | outcomes measured 24h post supplementation and compared with baseline values (at 0h) | 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 22 |
| Total | 22 |
Baseline characteristics
| Characteristic | Study Population |
|---|---|
| adenosine triphosphate | 57.5 U/L STANDARD_DEVIATION 11.35 |
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 22 Participants |
| Age, Continuous | 26.41 years STANDARD_DEVIATION 4.01 |
| Alanine aminotransferase | 19 U/L STANDARD_DEVIATION 9.2 |
| Albumin (g/L) | 46.59 g/L STANDARD_DEVIATION 2.52 |
| Aspartate Transferase | 19 U/L STANDARD_DEVIATION 4.22 |
| Bilirubin | 9.409 µmol/L STANDARD_DEVIATION 4.93 |
| body mass index | 23.45 kg/m2 STANDARD_DEVIATION 4.74 |
| Calcium | 2.407 mml/L STANDARD_DEVIATION 0.09 |
| Chloride ions | 102 mmol/L STANDARD_DEVIATION 2 |
| Cholesterol | 4.79 mmol/L STANDARD_DEVIATION 0.79 |
| Cholesterol -HDL ratio | 2.825 ratio STANDARD_DEVIATION 0.68 |
| Creatinine | 79.09 umol/L) STANDARD_DEVIATION 12.21 |
| estimated glomerular filtration rate | 78.38 ml/min/1.73m^2 STANDARD_DEVIATION 7.87 |
| Height | 1.70 meters STANDARD_DEVIATION 0.08 |
| Hematocrit | 0.428 L/L STANDARD_DEVIATION 0.04 |
| High density lipoprotein | 1.765 mmol/L STANDARD_DEVIATION 0.35 |
| Low density lipoprotein | 2.602 mmol/L STANDARD_DEVIATION 0.75 |
| non-HDL Cholesterol | 3.025 mmol/L STANDARD_DEVIATION 0.84 |
| Phosphate (mmol/L) | 1.13 mmol/L STANDARD_DEVIATION 0.14 |
| platelet counts | 258.6 cells 10^9 /L STANDARD_DEVIATION 60.69 |
| Potassium | 4.434 mmol/L STANDARD_DEVIATION 0.35 |
| Protein | 72.27 g/L STANDARD_DEVIATION 2.83 |
| Pulse | 65.59 bpm STANDARD_DEVIATION 7.64 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 4 Participants |
| Race (NIH/OMB) Black or African American | 0 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 | 0 Participants |
| Race (NIH/OMB) White | 18 Participants |
| Red blood cell count | 4.789 cells 10^12/L STANDARD_DEVIATION 0.42 |
| Region of Enrollment United Kingdom | 22 participants |
| Sex: Female, Male Female | 13 Participants |
| Sex: Female, Male Male | 9 Participants |
| Sodium | 140.4 mmol/L STANDARD_DEVIATION 2.59 |
| Systolic Blood Pressure | 118.2 mmHg STANDARD_DEVIATION 11.39 |
| Triglycerides | 0.929 mmol/L STANDARD_DEVIATION 0.3 |
| Urate | 284.3 µmol/L STANDARD_DEVIATION 59.13 |
| Urea | 4.818 mmol/L STANDARD_DEVIATION 1.39 |
| Weight | 68.54 Kg STANDARD_DEVIATION 18.16 |
| White blood cell count | 6.195 cells*10^6/L STANDARD_DEVIATION 1.46 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 |
| other Total, other adverse events | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 |
| serious Total, serious adverse events | 0 / 22 | 0 / 22 | 0 / 22 | 0 / 22 |
Outcome results
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.
Time frame: outcomes will be measured 24h post supplementation and compared with baseline values (0h)
Population: healthy volunteers
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Increase in the Average Peripheral Blood SPM Levels | 56.49 pg/mL | Standard Deviation 42.54 |
| Dose 1 | Increase in the Average Peripheral Blood SPM Levels | 56.91 pg/mL | Standard Deviation 38.5 |
| Dose 2 | Increase in the Average Peripheral Blood SPM Levels | 108.8 pg/mL | Standard Deviation 110.3 |
| Dose 3 | Increase in the Average Peripheral Blood SPM Levels | 139.7 pg/mL | Standard Deviation 83.44 |
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.
Time frame: outcomes measured 24h post supplementation and compared with baseline values (at 0h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | 31.97 percent change from baseline values | Standard Error 8.556 |
| Dose 1 | Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | 30.90 percent change from baseline values | Standard Error 8.379 |
| Dose 2 | Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | 6.723 percent change from baseline values | Standard Error 5.859 |
| Dose 3 | Changes in the Expression of Peripheral Blood Neutrophil Activation Markers | 13.93 percent change from baseline values | Standard Error 6.177 |
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.
Time frame: Outcomes will be measured 24h post supplementation and compared with baseline values (at 0h)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Placebo | Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | 23.19 percent change from baseline | Standard Error 12.9 |
| Dose 1 | Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | 70.01 percent change from baseline | Standard Error 28.31 |
| Dose 2 | Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | 22.60 percent change from baseline | Standard Error 12.26 |
| Dose 3 | Percentage Change in Omega-3 Fatty Acid Levels From Baseline After 24 Hours | 89.12 percent change from baseline | Standard Error 48.61 |