Cardiovascular DiseasePhase 3NCT01078909
Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation
A Phase 3 study testing Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) in people with Cardiovascular Disease and Inflammation, run by Penn State University at 1 site in United States.
Trial summary
The purpose of this study is to determine the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response to in vivo and ex vivo endotoxin challenge as measured by the production over time of several inflammatory markers. Read more about this study
- Who is it for?
- Ages 20 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Disease, Inflammation
- What is being tested?
- Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 125 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2011to Apr 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy men and non-pregnant/lactating women between the ages of 20 and 45
- BMI >19.9 and <30.0
- Able to give written informed consent and willing to comply with all study- related procedures.
Who cannot join
- Previous history of heart disease or diabetes
- Renal Insufficiency
- Chronic anti-inflammatory use
- Systolic blood pressure < 90
- Individuals currently using tobacco products or have done so in the previous 30 days
- Individuals taking Omega-3 fatty acid supplements or their usual intake of fish is greater than 3-4 servings per month.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State University
University Park, Pennsylvania, 16802
About this study
The purpose of this study is to determine the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response to in vivo and ex vivo endotoxin challenge as measured by the production over time of several inflammatory markers.
Read the detailed description
Inflammation is an important biological process initiated by the immune system in response to injury, irritation or infection. Prolonged or chronic inflammation is involved in the etiology of several diseases such as cardiovascular disease (CVD), diabetes, rheumatoid arthritis, cancer, and neurodegenerative diseases such as Alzheimer disease. The evidence base clearly demonstrates benefits of diet in ameliorating inflammation and reducing the burden of chronic disease. With respect to marine-derived omega-3 fatty acids and various markers of inflammation related to cardiovascular disease (CVD), both population studies and randomized controlled supplementation trials have yielded mixed results.
Some studies have demonstrated a dose-response relationship between dietary eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and increased membrane (phospholipid) EPA and DHA. Red blood cell (RBC) EPA + DHA content has been proposed as a potential, modifiable marker for coronary heart disease (CHD) risk. It is well established that these fatty acids are precursors of series-3 prostanoids, thromboxanes, 5-series leukotrienes, and novel lipid mediators such as resolvins and protectins that have anti-inflammatory effects. We hypothesize that nutritionally-relevant intakes of omega-3 fatty acids are able to blunt the usual response to an inflammatory stimulus. We propose to test this hypothesis using both in vivo (i.v. endotoxin challenge) and ex vivo (endotoxin-stimulated monocytes) models in a 6-month, dose-response study with marine-derived omega-3 fatty acid supplements in healthy volunteers.
- Conditions
- Cardiovascular Disease, Inflammation
- Being tested
- Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)
- Keywords
- Cardiovascular disease, Inflammation, Fish Oil, Omega-3 Fatty Acids, LPS, Endotoxin
- Medical subject headings
- Cardiovascular Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)Biological
Also called Omega-3 Fatty Acids, Fish Oil
Comparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period
| Study group | Role | What they receive |
|---|---|---|
| 300mg Fish Oil (EPA + DHA) Supplement | Experimental | Not described Receives: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 600mg Fish Oil (EPA+DHA) Supplement | Experimental | Not described Receives: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 900mg Fish Oil (EPA + DHA) Supplement | Experimental | Not described Receives: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 1800mg Fish Oil (EPA + DHA) Supplement | Experimental | Not described Receives: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| Placebo | Placebo comparator | Not described Receives: Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment
Measured: 5 months
Mean Concentrations of CRP Following 5 Months of Treatment
Measured: 5 months
Secondary outcomes (1)
Change in Lipid Mediators
0 Participants Analyzed; Lipid mediators were unable to be detected therefore there are no data to report.
Measured: 1, 2, 3 and 5 days post LPS administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Mar 2010 (estimated)
- Study startOct 2011
- Primary completionNov 2012
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Cardiovascular DiseaseStudies of the same condition, open and under way.
- More trials run by Penn State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 125 participants (actual)
Sponsor and investigators
- Lead sponsor
- Penn State University
- Sponsor type
- University, hospital or other
- Collaborators
- United States Department of Agriculture (USDA)
- Responsible party
- Sponsor
- Investigators
- Gordon L Jensen, MD, PhD, Principal investigator, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01078909
- Sponsor's protocol ID
- PKE LPS
- Status last verified
- Aug 2023
- First submitted
- 1 Mar 2010
- Last updated
- 21 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Flock MR, Skulas-Ray AC, Harris WS, Etherton TD, Fleming JA, Kris-Etherton PM. Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J Am Heart Assoc. 2013 Nov 19;2(6):e000513. doi: 10.1161/JAHA.113.000513.
PubMed 24252845
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Response Effects of Marine Omega-3 Fatty Acids on Inflammation
- ClinicalTrials.gov ID
- NCT01078909
- Acronym / sponsor ID
- PKE LPS
- Conditions
- Cardiovascular Disease, Inflammation
- Keywords
- Cardiovascular disease, Inflammation, Fish Oil, Omega-3 Fatty Acids, LPS, Endotoxin
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 125 participants (actual)
- Lead sponsor
- Penn State UniversityUniversity, hospital or other
- Collaborators
- United States Department of Agriculture (USDA)
- Study start
- Oct 2011
- Primary completion
- Nov 2012 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 2 Mar 2010 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine the lowest effective dose of EPA + DHA (300, 600, 900 and 1,800 mg/day delivered as fish oil supplements) that significantly attenuates the inflammatory response to in vivo and ex vivo endotoxin challenge as measured by the production over time of several inflammatory markers.
Detailed description
Inflammation is an important biological process initiated by the immune system in response to injury, irritation or infection. Prolonged or chronic inflammation is involved in the etiology of several diseases such as cardiovascular disease (CVD), diabetes, rheumatoid arthritis, cancer, and neurodegenerative diseases such as Alzheimer disease. The evidence base clearly demonstrates benefits of diet in ameliorating inflammation and reducing the burden of chronic disease. With respect to marine-derived omega-3 fatty acids and various markers of inflammation related to cardiovascular disease (CVD), both population studies and randomized controlled supplementation trials have yielded mixed results.
Some studies have demonstrated a dose-response relationship between dietary eicosapentaenoic acid and docosahexaenoic acid (EPA + DHA) and increased membrane (phospholipid) EPA and DHA. Red blood cell (RBC) EPA + DHA content has been proposed as a potential, modifiable marker for coronary heart disease (CHD) risk. It is well established that these fatty acids are precursors of series-3 prostanoids, thromboxanes, 5-series leukotrienes, and novel lipid mediators such as resolvins and protectins that have anti-inflammatory effects. We hypothesize that nutritionally-relevant intakes of omega-3 fatty acids are able to blunt the usual response to an inflammatory stimulus. We propose to test this hypothesis using both in vivo (i.v. endotoxin challenge) and ex vivo (endotoxin-stimulated monocytes) models in a 6-month, dose-response study with marine-derived omega-3 fatty acid supplements in healthy volunteers.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| 300mg Fish Oil (EPA + DHA) Supplement | Experimental | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 600mg Fish Oil (EPA+DHA) Supplement | Experimental | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 900mg Fish Oil (EPA + DHA) Supplement | Experimental | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| 1800mg Fish Oil (EPA + DHA) Supplement | Experimental | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
| Placebo | Placebo comparator | Biological: Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Healthy men and non-pregnant/lactating women between the ages of 20 and 45
- BMI >19.9 and <30.0
- Able to give written informed consent and willing to comply with all study- related procedures.
Key exclusion criteria (6 listed)
- Previous history of heart disease or diabetes
- Renal Insufficiency
- Chronic anti-inflammatory use
- Systolic blood pressure < 90
- Individuals currently using tobacco products or have done so in the previous 30 days
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA)Also: Omega-3 Fatty Acids, Fish OilComparison of 4 doses of EPA+DHA on in vivo and ex vivo (monocytes) response to an inflammatory stimulus (endotoxin) following a 6 month supplementation period | Biological | 1800mg Fish Oil (EPA + DHA) Supplement, 300mg Fish Oil (EPA + DHA) Supplement, 600mg Fish Oil (EPA+DHA) Supplement, 900mg Fish Oil (EPA + DHA) Supplement, Placebo |
Primary outcome
Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment
Time frame: 5 months
Mean Concentrations of CRP Following 5 Months of Treatment
Time frame: 5 months
1 secondary outcome
Change in Lipid Mediators
Time frame: 1, 2, 3 and 5 days post LPS administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 24252845Flock MR, Skulas-Ray AC, Harris WS, Etherton TD, Fleming JA, Kris-Etherton PM. Determinants of erythrocyte omega-3 fatty acid content in response to fish oil supplementation: a dose-response randomized controlled trial. J Am Heart Assoc. 2013 Nov 19;2(6):e000513. doi: 10.1161/JAHA.113.000513.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Gordon L Jensen, MD, PhD principal investigator
Penn State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eicosapentaenoic Acid and Docosahexaenoic Acid (EPA + DHA) in people with Cardiovascular Disease and Inflammation, run by Penn State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 14 Jun 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mean Concentrations of Inflammatory Markers (TNF-alpha and IL-6) Following 5 Months of Treatment (time frame: 5 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01078909, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2023.