Fish Oil-derived N-3 Polyunsaturated Fatty Acids and Extracellular Vesicles (HI-FIVE)

November 4, 2022 updated by: Professor Parveen Yaqoob, MA, DPhil, RNutr, FAfN, University of Reading

Effects of Fish Oil-derived N-3 Polyunsaturated Fatty Acids on the Generation and Functional Activities of Extracellular Vesicles

N-3 polyunsaturated fatty acids (n-3 PUFA), which are abundant in oily fish and fish oils, have been suggested to play a role in reducing the risk of cardiovascular diseases (CVDs) by modifying a wide range of risk factors, such as blood fats, blood clotting, blood vessel function and inflammation. Extracellular vesicles (EVs) are small particles released from various cells when they are activated or damaged. High numbers of EVs in the blood have been associated with a higher risk of CVDs, and it is thought that this is because they carry 'bioactive' components which can affect many processes involved in CVDs. However, very few clinical trials have investigated the relationships between the consumption of n-3 PUFA and circulating EVs. This study aims to investigate the effects of dietary n-3 PUFA on the generation and functional activities of EVs, which would provide new insight into the benefits of n-3 PUFA on cardiovascular health.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

The proposed study will be a randomised, double-blind, placebo-controlled crossover intervention. Subjects (40-70y) at moderate CVDs risk will be supplemented with either fish oil (1.8 g/d n-3 PUFA) or placebo (high-oleic safflower oil) for 12 weeks. After a 12-week washout and then cross-over to the other intervention for another 12 weeks. Blood samples will be collected before and after each intervention. A food frequency questionnaire will be administered to assess the subject's habitual intake of n-3 PUFA. Subjects will also be expected to maintain a low consumption of n-3 fatty acids, refrain from the use of all supplements, and maintain their body weight during the study. The dose is based on our previous work, which demonstrated a reduction in numbers of endothelial-derived EVs (EEVs) and a trend for reduced numbers of platelet-derived EVs (PEVs), and a dose at which beneficial effects of n-3 PUFA on plaque stability are reported. The experimental work will follow two main strands. The first strand will examine the influence of n-3 PUFA supplementation on the characteristics and functional activities of total EVs from plasma. The second strand will examine the influence of n-3 PUFA on the generation of PEVs from platelets taken from subjects and stimulated in vitro; the PEVs generated will subsequently be assessed for their composition and functional activity. This experimental design will allow simultaneous investigation of both the composition and activity of total EVs taken directly from blood, and the generation and activity of PEVs. Based on our previous work, 27 subjects are required to detect a 10% reduction in numbers of EVs following fish oil supplementation with a two-sided significance level of 5% and a power of 90%, and 34 subjects are required for a power of 95%. Also based on previous data, 22 subjects would give 95% power to detect 10% differences in thrombus formation and 30 subjects are required to detect a significant effect of n-3 PUFA on platelet aggregation and phosphatidylserine (PS) exposure. Allowing for a 15% dropout rate, and aiming for 95% power based on a 10% reduction in EVs numbers, we will therefore recruit 40 subjects in total.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
42

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • Reading, United Kingdom, RG6 6AP
        • University of Reading

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

40 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Aged 40-70 years
  • Non-smoker

  • At moderate risk of cardiovascular diseases

    • The risk will be evaluated by an online calculator called "QRISK2". This online calculator (https://qrisk.org/2016/), which use traditional risk factors (age, systolic blood pressure, smoking status and ratio of total serum cholesterol to high-density lipoprotein cholesterol) together with body mass index, ethnicity, measures of deprivation, family history, will provide a percentage of risk of having a heart attack or stroke within the next 10 years.
    • Subjects with 10%-20% will be regarded as being at moderate risk

Exclusion Criteria:

  • BMI: <18.5 kg/m2
  • Anaemia (haemoglobin concentration <12.5 g/L in men and<11.5 g/L in women)
  • Hyperlipidaemia (total cholesterol concentration >8 mmol/L)
  • Diabetes (diagnosed or fasting glucose concentration >7 mmol/L) or other endocrine disorders
  • Angina, stroke, or any vascular disease in the past 12 months
  • Renal, gastrointestinal, respiratory, liver or bowel disease
  • Inflammatory disease
  • Take drug treatment for hypertension, hyperlipidaemia, inflammation, depression or thyropathy.
  • Take aspirin, ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs) > 4 times per month, or once in the week preceding the study
  • Take any other anti-platelet or anti-coagulant drugs, like triflusal, clopidogrel and warfarin.
  • Have allergies
  • Smoking (including e-cigarettes and nicotine products)
  • Alcohol misuse or intakes >21 units/wk for men and >15 units/wk for women or have a history of alcohol misuse
  • Regularly consume oily fish and/or dietary supplements
  • Planning to start or on a weight reducing regimen
  • Intense aerobic exercise (>20 min, three times a week)
  • Females who are pregnant, lactating, or if of reproductive age and not using a reliable form of contraception (including abstinence)
  • Have participated in another clinical trial within the last three months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: TRIPLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
ACTIVE_COMPARATOR: Intervention
Fish oil capsules
Dietary supplement: Fish oil capsules
Each serving contains 360mg eicosapentaenoic acid (EPA), 270mg docosahexaenoic acid (DHA) and total supplement is 1.8 g per day n-3 PUFA for 12 weeks
PLACEBO_COMPARATOR: Placebo
High-oleic safflower oil capsules
Dietary supplement: High-oleic safflower oil capsules
High-oleic safflower oil capsules for 12 weeks

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Numbers of Circulating Total EVs in Platelet-free Plasma (PFP) Detected by Nanoparticle Tracking Analysis (NTA)
Time Frame: Change of circulating total EV numbers in PFP detected by NTA after intake period of 12 weeks
Circulating EVs were first isolated to obtain fractions 7~9 by size exclusion chromatography (SEC) using Izon qEV columns (Izon Science Ltd, Oxford, United Kingdom). Fractions were then diluted with PBS to maintain the recommended concentration range of particles (1~10*10^8 vesicles/ml) before being analysed on NanoSight 300 (Malvern, Amesbury, United Kingdom). For each analysis, five videos, each of 60 seconds duration, were captured with the camera level at 13. Data were analysed using the instrument software NTA 3.20, which can identify individual particles and estimate their sizes based on the Stokes-Einstein Equation. Finally, a threshold of 70nm was set for NTA to ensure minimal interference by small lipoproteins.
Change of circulating total EV numbers in PFP detected by NTA after intake period of 12 weeks
Numbers of Total Phosphatidylserine Positive EVs (PS+EVs) in Platelet-free Plasma (PFP) Detected by Flow Cytometry (FCM)
Time Frame: Change of total PS+EV numbers in PFP detected by FCM after intake period of 12 weeks
A 5μl of PFP was added into nonsticky microcentrifuge tubes (Alpha Laboratories Ltd, Hampshire, United Kingdom), which contained 5μl FcR blocking reagent (Miltenyi Biotec Ltd, Surrey, United Kingdom) and Annexin V buffer and incubated for 15 minutes in the dark at room temperature. Antibodies and isotype-matched controls were then added and samples incubated for another 15 minutes in the dark at room temperature. After incubation, samples were diluted with 200μl Annexin V buffer and transferred into FACS flow tubes (BD Biosciences, Wokingham, United Kingdom), ready to be analysed by FCM. PS+EVs were identified as Annexin V+EVs when triggering on APC fluorescence.
Change of total PS+EV numbers in PFP detected by FCM after intake period of 12 weeks
Characterisation of Circulating EVs Subpopulation in PFP Detected by Fluorescence FCM
Time Frame: Change in the numbers of circulating EVs subpopulation in PFP by fluorescence FCM after intake period of 12 weeks
A 5μl of PFP was added into nonsticky microcentrifuge tubes (Alpha Laboratories Ltd, Hampshire, United Kingdom), which contained 5μl FcR blocking reagent (Miltenyi Biotec Ltd, Surrey, United Kingdom) and Annexin V buffer and incubated for 15 minutes in the dark at room temperature. Antibodies and isotype-matched controls were then added and samples incubated for another 15 minutes in the dark at room temperature. After incubation, samples were diluted with 200μl Annexin V buffer and transferred into FACS flow tubes (BD Biosciences, Wokingham, United Kingdom), ready to be analysed by FCM. Platelet-derived EVs (PDEVs) were identified as Annexin V+EVs which also stained positive for CD41-PE in APC vs PE quadrant plot, and endothelial-derived EVs (EDEVs) were identified as Annexin V+EVs which also stained positive for CD105- eFluor450 in APC vs PB quadrant plot.
Change in the numbers of circulating EVs subpopulation in PFP by fluorescence FCM after intake period of 12 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Pro-thrombotic Activities of Circulating EVs in PFP (Lag Time for Thrombin Generation)
Time Frame: Change of pro-thrombotic activities (lag time for thrombin generation)of circulating EVs in PFP after intake period of 12 weeks
A commercially available, plate-based thrombin generation assay was used to measure thrombin generation in either a standard, pooled vesicle and platelet-free plasma (termed vesicle-free plasma or VFP) or in the same VFP but with added circulating EVs from subjects in the intervention study. This enabled the assessment of TF-dependent thrombin generation specifically attributed to circulating EVs in samples from the intervention study. Results were presented as five variables: (i) lag-phase for initiation of thrombin generation after addition of the trigger (time to 1/6 of the peak height) (min); (ii) peak thrombin concentration (nM); (iii) time to reach the peak (min); (iv) velocity index, defined as = [peak height/(time to peak - lag time)] and (v) area under the curve, defined as endogenous thrombin potential (ETP) (expressed as nM thrombin × min)
Change of pro-thrombotic activities (lag time for thrombin generation)of circulating EVs in PFP after intake period of 12 weeks
Pro-thrombotic Activities of Circulating EVs in PFP (Peak Thrombin Concentration)
Time Frame: Change of pro-thrombotic activities (peak thrombin concentration) of circulating EVs in PFP after intake period of 12 weeks
A commercially available, plate-based thrombin generation assay was used to measure thrombin generation in either a standard, pooled vesicle and platelet-free plasma (termed vesicle-free plasma or VFP) or in the same VFP but with added circulating EVs from subjects in the intervention study. This enabled the assessment of TF-dependent thrombin generation specifically attributed to circulating EVs in samples from the intervention study. Results were presented as five variables: (i) lag-phase for initiation of thrombin generation after addition of the trigger (time to 1/6 of the peak height) (min); (ii) peak thrombin concentration (nM); (iii) time to reach the peak (min); (iv) velocity index, defined as = [peak height/(time to peak - lag time)] and (v) area under the curve, defined as endogenous thrombin potential (ETP) (expressed as nM thrombin × min)
Change of pro-thrombotic activities (peak thrombin concentration) of circulating EVs in PFP after intake period of 12 weeks
Pro-thrombotic Activities of Circulating EVs in PFP (Time to Peak Thrombin Concentration)
Time Frame: Change of pro-thrombotic activities (time to peak thrombin concentration) of circulating EVs in PFP after intake period of 12 weeks
A commercially available, plate-based thrombin generation assay was used to measure thrombin generation in either a standard, pooled vesicle and platelet-free plasma (termed vesicle-free plasma or VFP) or in the same VFP but with added circulating EVs from subjects in the intervention study. This enabled the assessment of TF-dependent thrombin generation specifically attributed to circulating EVs in samples from the intervention study. Results were presented as five variables: (i) lag-phase for initiation of thrombin generation after addition of the trigger (time to 1/6 of the peak height) (min); (ii) peak thrombin concentration (nM); (iii) time to reach the peak (min); (iv) velocity index, defined as = [peak height/(time to peak - lag time)] and (v) area under the curve, defined as endogenous thrombin potential (ETP) (expressed as nM thrombin × min)
Change of pro-thrombotic activities (time to peak thrombin concentration) of circulating EVs in PFP after intake period of 12 weeks
Pro-thrombotic Activities of Circulating EVs in PFP (Velocity Index)
Time Frame: Change of pro-thrombotic activities (velocity index) of circulating EVs in PFP after intake period of 12 weeks
A commercially available, plate-based thrombin generation assay was used to measure thrombin generation in either a standard, pooled vesicle and platelet-free plasma (termed vesicle-free plasma or VFP) or in the same VFP but with added circulating EVs from subjects in the intervention study. This enabled the assessment of TF-dependent thrombin generation specifically attributed to circulating EVs in samples from the intervention study. Results were presented as five variables: (i) lag-phase for initiation of thrombin generation after addition of the trigger (time to 1/6 of the peak height) (min); (ii) peak thrombin concentration (nM); (iii) time to reach the peak (min); (iv) velocity index, defined as = [peak height/(time to peak - lag time)] and (v) area under the curve, defined as endogenous thrombin potential (ETP) (expressed as nM thrombin × min)
Change of pro-thrombotic activities (velocity index) of circulating EVs in PFP after intake period of 12 weeks
Pro-thrombotic Activities of Circulating EVs in PFP (Endogenous Thrombin Potential)
Time Frame: Change of pro-thrombotic activities (endogenous thrombin potential) of circulating EVs in PFP after intake period of 12 weeks
A commercially available, plate-based thrombin generation assay was used to measure thrombin generation in either a standard, pooled vesicle and platelet-free plasma (termed vesicle-free plasma or VFP) or in the same VFP but with added circulating EVs from subjects in the intervention study. This enabled the assessment of TF-dependent thrombin generation specifically attributed to circulating EVs in samples from the intervention study. Results were presented as five variables: (i) lag-phase for initiation of thrombin generation after addition of the trigger (time to 1/6 of the peak height) (min); (ii) peak thrombin concentration (nM); (iii) time to reach the peak (min); (iv) velocity index, defined as = [peak height/(time to peak - lag time)] and (v) area under the curve, defined as endogenous thrombin potential (ETP) (expressed as nM thrombin × min)
Change of pro-thrombotic activities (endogenous thrombin potential) of circulating EVs in PFP after intake period of 12 weeks
Ex Vivo Agonist-stimulated Platelet Activation Detected by Plate-based Platelet Aggregation Assay
Time Frame: Change in ex vivo platelet activation after intake period of 12 weeks
96-well high-throughput aggregometry technique, allowing testing of a wide range of concentrations of different agonists, was used to examine the influence of n-3 PUFA supplementation on platelet function. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) from each study visit was used in the platelet aggregation assay using pre-prepared 96-well microplates, containing the agonists (ADP, EPI, TRAP-6 and U46619). Dose-response curves in response to each agonist were obtained and results were represented as a LogEC50 (log concentration of agonist, M, giving a response halfway between maximum and minimum aggregation).
Change in ex vivo platelet activation after intake period of 12 weeks
Ex Vivo Agonist-stimulated Platelet Activation Detected by Plate-based Platelet Aggregation Assay (CRP-XL Log EC50)
Time Frame: Change in ex vivo platelet activation after intake period of 12 weeks
96-well high-throughput aggregometry technique, allowing testing of a wide range of concentrations of different agonists, was used to examine the influence of n-3 PUFA supplementation on platelet function. Platelet-rich plasma (PRP) and platelet-poor plasma (PPP) from each study visit was used in the platelet aggregation assay using pre-prepared 96-well microplates, containing the agonists (CRP-XL). Dose-response curves in response to each agonist were obtained and results were represented as a LogEC50 (log concentration of agonist, mg/ml, giving a response halfway between maximum and minimum aggregation).
Change in ex vivo platelet activation after intake period of 12 weeks
Pro-thrombotic Activities of Platelet-derived Extracellular Vesicles (PDEVs) Prepared From the Supernatants of Stimulated Platelets (Endpoint and Maximum of Thrombus Formation)
Time Frame: Change in pro-thrombotic activities (endpoint and maximum of thrombus formation)of PEVs prepared from the supernatants of stimulated platelets after intake period of 12 weeks
Ex vivo thrombus formation was measured by the addition of in vitro-generated PDEVs from stimulated platelets into whole blood under flow. Results were presented as three variables: (i) endpoint for ex vivo thrombus formation (FU); (ii) endpoint for ex vivo thrombus formation (FU); (iii) area under curve.
Change in pro-thrombotic activities (endpoint and maximum of thrombus formation)of PEVs prepared from the supernatants of stimulated platelets after intake period of 12 weeks
Pro-thrombotic Activities of Platelet-derived Extracellular Vesicles (PDEVs) Prepared From the Supernatants of Stimulated Platelets (Area Under Curve)
Time Frame: Change in pro-thrombotic activities (area under curve) of PEVs prepared from the supernatants of stimulated platelets after intake period of 12 weeks
Ex vivo thrombus formation was measured by the addition of in vitro-generated PDEVs from stimulated platelets into whole blood under flow. Results were presented as three variables: (i) endpoint for ex vivo thrombus formation (FU); (ii) endpoint for ex vivo thrombus formation (FU); (iii) area under curve.
Change in pro-thrombotic activities (area under curve) of PEVs prepared from the supernatants of stimulated platelets after intake period of 12 weeks
Circulating EV Total Lipids Analysis
Time Frame: Change in total lipids of EVs after intake period of 12 weeks
A 500μl aliquot of frozen PFP was defrosted at room temperature using a roller mixer and subjected to SEC for the isolation and purification of EVs. The fractions 7~9 were pooled together, and 800μl of pooled fractions was prepared for total lipid extraction and methyl esterification. The EV total lipid methyl esters were then analysed by gas chromatography on a Hewlett-Packard 6890 series GC (Hewlett-Packard, California, United States), with the following protocol: split ratio was set as 30:1 for plasma and EV analysis. The injection volume was 1μl for plasma and 5μl for EVs, respectively. The temperature of both injector and detector were kept at 300°C and the temperature program was initial temperature 115°C for 2 minutes, increased at 10 °C/min to 200°C and hold at this temperature for 16 minutes, and finally increased at 60°C/min to 240°C for 2 minutes (total run time: 29.2 minutes). Samples were analysed by using ChemStation software and Microsoft Excel.
Change in total lipids of EVs after intake period of 12 weeks
Plasma Total Phospholipids Analysis
Time Frame: Change of plasma total phospholipids after intake period of 12 weeks
A 400μl aliquot of frozen PFP was defrosted and centrifuged to remove denatured protein. The 400μl of 0.9% NaCl was added to the PFP sample to make up 800μl in total, and 30μg of phosphatidylcholine (PC) and 15μg of phosphatidylethanolamine (PE) internal standards were then added for the quantitative analysis. After lipid extraction, separation of PC and PE, and methyl esterification of plasma phospholipid extracts, samples were analysed by GC.
Change of plasma total phospholipids after intake period of 12 weeks
Concentrations of Lipid Profile in Plasma
Time Frame: Change in concentrations of plasma lipid profile after intake period of 12 weeks
A 250μl aliquot of frozen PFP was defrosted at room temperature using a roller mixer and centrifuged at 500xg for 5 minutes at room temperature (Eppendorf Centrifuge 5415 R, DJBlabcare, United Kingdom). Then the sample was analysed by a RANDOX clinical analyser (RANDOX Daytona+ Analyser, Randox Laboratories Ltd, United Kingdom) for the concentration of TC, TAG, HDL-C, LDL-C and TC/HDL-C ratio.
Change in concentrations of plasma lipid profile after intake period of 12 weeks
Concentrations of TC/HDL-C Ratio in Plasma
Time Frame: Change in concentrations of plasma TC/HDL-C ratio after intake period of 12 weeks
A 250μl aliquot of frozen PFP was defrosted at room temperature using a roller mixer and centrifuged at 500xg for 5 minutes at room temperature (Eppendorf Centrifuge 5415 R, DJBlabcare, United Kingdom). Then the sample was analysed by a RANDOX clinical analyser (RANDOX Daytona+ Analyser, Randox Laboratories Ltd, United Kingdom) for TC/HDL-C ratio.
Change in concentrations of plasma TC/HDL-C ratio after intake period of 12 weeks
Blood Pressure
Time Frame: Change in blood pressure after intake period of 12 weeks
Subjects were asked to have a rest for 10 mins before blood pressure detection, and then blood pressure cuff was placed firmly on their upper left arms approximately 2 cm above the elbow with the indicator mark on the cuff over the brachial artery to start measurement. Subjects should put their arms at the level of the heart and should not speak and cross their legs during the measurement. Measurement was performed three times and waited for 2 mins between each reading ((Omron M2 Upper Arm Blood Pressure Monitor, OMRON Healthcare Europe BV, United Kingdom). The average of the three readings was taken to obtain the final result.
Change in blood pressure after intake period of 12 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Reading

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Biotechnology and Biological Sciences Research Council

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Parveen Yaqoob, MA, DPhil, RNutr, University of Reading

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 16, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2019

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
March 30, 2021

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
June 23, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 27, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
June 29, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 7, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
November 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • UREC 17/18

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

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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