Inflammatory ResponsesPRONOVANCT01813110
Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation
A study testing 4 g prescription omega-3 concentrate in people with Inflammatory Responses, run by Penn State University at 1 site in United States.
Trial summary
The purpose of this study is to assess whether the marine omega-3 fatty acids can attenuate inflammatory responses to endotoxin challenge. Read more about this study
- Who is it for?
- Ages 20 to 45 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Inflammatory Responses
- What is being tested?
- 4 g prescription omega-3 concentrate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 21 participants
- Where
- 1 siteUnited States
- Study dates
- May 2014to Apr 2015
- Phase
- Interventional
- 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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Men between the ages of 20 and 45.
- BMI ≥20 and ≤30
- Participants who are able to give written informed consent and willing to comply with all study-related procedures.
- Any race or ethnic background is acceptable
- Non-smoking
- The specific exclusion criteria are:
Show all 35Show fewer
- Previous history of vasovagal reactions or unprovoked fainting (I.e. fainting as a result of prolonged standing, exercise)
- Resting heart rate < 55 bpm
- History of atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
- History of diabetes mellitus (and/or a fasting glucose >126 mg/dL at screening)
- Chronic anti-inflammatory medication use or treatment with aspirin, NSAIDs, COX-2 inhibitors; steroids or any immunomodulatory therapy 2 weeks prior to the screening visit
- Self-reported history of allergy to fish
- History of a non-skin malignancy within the previous 5 years
- Renal insufficiency as defined by creatinine outside of lab defined normal range at Screening Visit
- History of liver disease or abnormal LFTs (AST, ALT, Alk. Phos., GGT > 1.5x ULN; bilirubin > 2x ULN) at Screening Visit
- Total white blood cell count less than or equal to 3.0 THO/uL
- Hemoglobin less than 11.0 g/dL
- Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection
- Self-reported history of HIV positive
- Participants who have undergone any organ transplant
- Individuals who currently use tobacco products or have done so in the previous 30 days.
- Participants who are unwilling to discontinue use of nutritional supplements, herbs or vitamins unless approved by study staff.
- Participants who are unwilling to eliminate omega-3 fatty acid (EPA + DHA) supplements and/or fortified food, or have a usual intake of high omega-3 fish (tuna and other non-fried fish) > 2 servings per week
- Elevated blood pressure (BP > 159/99) or use of any anti-hypertensive medications.
- Latex allergy
- Unwillingness to refrain from blood donation for 2 months prior to and following endotoxin administration
- Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator
- Inability to take study capsules
- History of severe, repeated headaches
- History of migraine
- Medical condition that causes severe nausea or vomiting
- Low resting blood pressure (SBP < 90 mmHg)
- History of atrial fibrillation/flutter
- Abnormal coagulation parameters (platelet count, prothrombin time with INR), documented coagulation abnormality, or use of anticoagulant medication
- High LDL-C (> or = 160 mg/dL)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Penn State University
University Park, Pennsylvania, 16802
About this study
Official title: Effects of a Prescription Omega-3 Fatty Acid Concentrate in a Placebo-controlled Trial of Human Endotoxemia
The purpose of this study is to assess whether the marine omega-3 fatty acids can attenuate inflammatory responses to endotoxin challenge.
Read the detailed description
Controlled endotoxin infusion has been used widely as a model system to evaluate anti-inflammatory mediators and therapies in a controlled, in vivo setting. It is well established that infusion of bacterial endotoxin (also known as lipopolysaccharide or LPS) in humans results in a marked increase in inflammatory cytokines, most notably TNF-α, IL-1, IL-6 and IL-8, CRP, granulocyte colony stimulating factor (GCSF); eicosanoids, such as prostaglandin (PG) E2 and other mediators. Administration of endotoxin, even at a low dose (0.6 ng/kg) elevates circulating concentrations of inflammatory cytokines, and mimics the inflammatory effects of chronic diseases. This model has been used for decades and has proved to be safe and informative for evaluating anti-inflammatory therapeutic interventions on human inflammation and downstream consequences.
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's 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. It is well established that these omega-3 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 supplementation of omega-3 fatty acids will blunt the response to an inflammatory stimulus and/or enhance the resolution phase.
We propose to test this hypothesis using an in vivo endotoxin challenge with a pharmacological dose of omega-3 fatty acid ethyl esters (P-OM3, 3.4 g/d EPA + DHA) in healthy volunteers. Our proposed approach is novel in that we will provoke an in vivo inflammatory response by infusing human subjects with a low dose (0.6 ng/kg body weight) of sterile endotoxin (lipopolysaccharide [LPS]) in contrast to studies that have attempted to reverse established inflammatory pathology. Results from our proposed research will advance our understanding of the effect of omega-3 fatty acids on prevention/attenuation of an inflammatory response.
- Conditions
- Inflammatory Responses
- Being tested
- 4 g prescription omega-3 concentrate, Placebo
- Keywords
- inflammation, omega-3, fish oil
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4 g prescription omega-3 concentrateDrug
Also called Lovaza, Omacor
4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks
PlaceboDrug
Also called No other name (control)
olive oil
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Identical olive oil capsules Receives: Drug: Placebo |
| Omega-3 | Experimental | 4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks) Receives: Drug: 4 g prescription omega-3 concentrate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in C Reactive Protein (CRP)
Change in blood levels of CRP at 24 hours post endotoxin administration, after each 8 week intervention
Measured: 24 hours post endotoxin administration, following each 8 week intervention
Secondary outcomes (2)
Tumor Necrosis Factor-α (TNF-α)
Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention
Measured: 2 hours post endotoxin administration, following each 8 week intervention
Interleukin-6 (IL-6)
Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention
Measured: 2 hours post endotoxin administration, following each 8 week intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Mar 2013 (estimated)
- Study startMay 2014
- Primary completionApr 2015
- Study completionApr 2015
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.
- Other trials for Inflammatory ResponsesStudies 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Penn State University
- Sponsor type
- University, hospital or other
- Collaborators
- Pronova BioPharma
- Responsible party
- Sponsor
- Investigators
- Gordon Jensen, MD, PhD, Principal investigator, Penn State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01813110
- Sponsor's protocol ID
- PRONOVA
- Acronym
- PRONOVA
- Status last verified
- Aug 2023
- First submitted
- 14 Mar 2013
- Last updated
- 21 Aug 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
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
- Effects of a Prescription Omega-3 Fatty Acid Concentrate in a Placebo-controlled Trial of Human Endotoxemia
- ClinicalTrials.gov ID
- NCT01813110
- Acronym / sponsor ID
- PRONOVA / PRONOVA
- Conditions
- Inflammatory Responses
- Keywords
- inflammation, omega-3, fish oil
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Penn State UniversityUniversity, hospital or other
- Collaborators
- Pronova BioPharma
- Study start
- May 2014
- Primary completion
- Apr 2015 (actual)
- Study completion
- Apr 2015 (actual)
- First posted
- 18 Mar 2013 (estimated)
- Results
- Posted 1 Aug 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 assess whether the marine omega-3 fatty acids can attenuate inflammatory responses to endotoxin challenge.
Detailed description
Controlled endotoxin infusion has been used widely as a model system to evaluate anti-inflammatory mediators and therapies in a controlled, in vivo setting. It is well established that infusion of bacterial endotoxin (also known as lipopolysaccharide or LPS) in humans results in a marked increase in inflammatory cytokines, most notably TNF-α, IL-1, IL-6 and IL-8, CRP, granulocyte colony stimulating factor (GCSF); eicosanoids, such as prostaglandin (PG) E2 and other mediators. Administration of endotoxin, even at a low dose (0.6 ng/kg) elevates circulating concentrations of inflammatory cytokines, and mimics the inflammatory effects of chronic diseases. This model has been used for decades and has proved to be safe and informative for evaluating anti-inflammatory therapeutic interventions on human inflammation and downstream consequences.
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's 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. It is well established that these omega-3 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 supplementation of omega-3 fatty acids will blunt the response to an inflammatory stimulus and/or enhance the resolution phase.
We propose to test this hypothesis using an in vivo endotoxin challenge with a pharmacological dose of omega-3 fatty acid ethyl esters (P-OM3, 3.4 g/d EPA + DHA) in healthy volunteers. Our proposed approach is novel in that we will provoke an in vivo inflammatory response by infusing human subjects with a low dose (0.6 ng/kg body weight) of sterile endotoxin (lipopolysaccharide [LPS]) in contrast to studies that have attempted to reverse established inflammatory pathology. Results from our proposed research will advance our understanding of the effect of omega-3 fatty acids on prevention/attenuation of an inflammatory response.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboIdentical olive oil capsules |
| Omega-3 | Experimental | Drug: 4 g prescription omega-3 concentrate4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks) |
Who may qualify
- Ages
- 20 to 45 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (35 listed)
- Men between the ages of 20 and 45.
- BMI ≥20 and ≤30
- Participants who are able to give written informed consent and willing to comply with all study-related procedures.
- Any race or ethnic background is acceptable
- Non-smoking
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| 4 g prescription omega-3 concentrateAlso: Lovaza, Omacor4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks | Drug | Omega-3 |
| PlaceboAlso: No other name (control)olive oil | Drug | Placebo |
Primary outcome
Change in C Reactive Protein (CRP)
Time frame: 24 hours post endotoxin administration, following each 8 week intervention
Change in blood levels of CRP at 24 hours post endotoxin administration, after each 8 week intervention
2 secondary outcomes
Tumor Necrosis Factor-α (TNF-α)
Time frame: 2 hours post endotoxin administration, following each 8 week intervention
Interleukin-6 (IL-6)
Time frame: 2 hours post endotoxin administration, following each 8 week intervention
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.
- Individual participant dataSharing planned: No
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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 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 study testing 4 g prescription omega-3 concentrate in people with Inflammatory Responses, 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 35 inclusion and 0 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Aug 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?
Change in C Reactive Protein (CRP) (time frame: 24 hours post endotoxin administration, following each 8 week intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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.