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Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation (PRONOVA)

Primary Purpose

Inflammatory Responses

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
4 g prescription omega-3 concentrate
Placebo
Sponsored by
Penn State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Inflammatory Responses focused on measuring inflammation, omega-3, fish oil

Eligibility Criteria

20 Years - 45 Years (Adult)MaleAccepts Healthy Volunteers

Inclusion Criteria:

  1. Men between the ages of 20 and 45.
  2. BMI ≥20 and ≤30
  3. Participants who are able to give written informed consent and willing to comply with all study-related procedures.
  4. Any race or ethnic background is acceptable
  5. Non-smoking

The specific exclusion criteria are:

  1. Previous history of vasovagal reactions or unprovoked fainting (I.e. fainting as a result of prolonged standing, exercise)
  2. Resting heart rate < 55 bpm
  3. History of atherosclerotic cardiovascular disease, including coronary disease, cerebrovascular disease, or peripheral vascular disease
  4. History of diabetes mellitus (and/or a fasting glucose >126 mg/dL at screening)
  5. 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
  6. Self-reported history of allergy to fish
  7. History of a non-skin malignancy within the previous 5 years
  8. Renal insufficiency as defined by creatinine outside of lab defined normal range at Screening Visit
  9. History of liver disease or abnormal LFTs (AST, ALT, Alk. Phos., GGT > 1.5x ULN; bilirubin > 2x ULN) at Screening Visit
  10. Total white blood cell count less than or equal to 3.0 THO/uL
  11. Hemoglobin less than 11.0 g/dL
  12. Any major active rheumatologic, pulmonary, or dermatologic disease or inflammatory condition or minor active infection
  13. Self-reported history of HIV positive
  14. Participants who have undergone any organ transplant
  15. Individuals who currently use tobacco products or have done so in the previous 30 days.
  16. Participants who are unwilling to discontinue use of nutritional supplements, herbs or vitamins unless approved by study staff.
  17. 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
  18. Elevated blood pressure (BP > 159/99) or use of any anti-hypertensive medications.
  19. Latex allergy
  20. Unwillingness to refrain from blood donation for 2 months prior to and following endotoxin administration
  21. Any medical condition or abnormal laboratory value that is judged clinically significant by an investigator
  22. Inability to take study capsules
  23. History of severe, repeated headaches
  24. History of migraine
  25. Medical condition that causes severe nausea or vomiting
  26. Low resting blood pressure (SBP < 90 mmHg)
  27. History of atrial fibrillation/flutter
  28. Abnormal coagulation parameters (platelet count, prothrombin time with INR), documented coagulation abnormality, or use of anticoagulant medication
  29. High LDL-C (> or = 160 mg/dL)

Sites / Locations

  • Penn State University

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Omega-3

Arm Description

Identical olive oil capsules

4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks)

Outcomes

Primary Outcome Measures

Change in C Reactive Protein (CRP)
Change in blood levels of CRP at 24 hours post endotoxin administration, after each 8 week intervention

Secondary Outcome Measures

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
Interleukin-6 (IL-6)
Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention

Full Information

First Posted
March 14, 2013
Last Updated
August 16, 2023
Sponsor
Penn State University
Collaborators
Pronova BioPharma
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1. Study Identification

Unique Protocol Identification Number
NCT01813110
Brief Title
Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation
Acronym
PRONOVA
Official Title
Effects of a Prescription Omega-3 Fatty Acid Concentrate in a Placebo-controlled Trial of Human Endotoxemia
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Completed
Study Start Date
May 2014 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Penn State University
Collaborators
Pronova BioPharma

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Inflammatory Responses
Keywords
inflammation, omega-3, fish oil

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Identical olive oil capsules
Arm Title
Omega-3
Arm Type
Experimental
Arm Description
4 g prescription omega-3 concentrate (4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks)
Intervention Type
Drug
Intervention Name(s)
4 g prescription omega-3 concentrate
Other Intervention Name(s)
Lovaza, Omacor
Intervention Description
4 g/d prescription omega-3 fatty acid concentrate taken orally for 8-12 weeks
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
No other name (control)
Intervention Description
olive oil
Primary Outcome Measure Information:
Title
Change in C Reactive Protein (CRP)
Description
Change in blood levels of CRP at 24 hours post endotoxin administration, after each 8 week intervention
Time Frame
24 hours post endotoxin administration, following each 8 week intervention
Secondary Outcome Measure Information:
Title
Tumor Necrosis Factor-α (TNF-α)
Description
Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention
Time Frame
2 hours post endotoxin administration, following each 8 week intervention
Title
Interleukin-6 (IL-6)
Description
Change in the plasma concentration of TNF-α at 2 hours post endotoxin administration, after each 8 week intervention
Time Frame
2 hours post endotoxin administration, following each 8 week intervention

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: 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: 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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Gordon Jensen, MD, PhD
Organizational Affiliation
Penn State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Penn State University
City
University Park
State/Province
Pennsylvania
ZIP/Postal Code
16802
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

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Effects of a Prescription Omega-3 Fatty Acid Concentrate on Induced Inflammation

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