Effects of Fish Oil and Red Wine on Oxidative Stress Biomarkers

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2014 by University of Pennsylvania
Sponsor:
Collaborator:
American Heart Association
Information provided by (Responsible Party):
Carsten Skarke, University of Pennsylvania
ClinicalTrials.gov Identifier:
NCT00682318
First received: May 16, 2008
Last updated: February 5, 2014
Last verified: February 2014
  Purpose

The American Heart Association and the American College of Cardiology (AHA/ACC) recently encouraged "increased consumption of omega-3 fatty acids in the form of fish or capsule form (1 g/day) for risk reduction" and stated that "for treatment of elevated triglycerides, higher doses are usually necessary for risk reduction" (Smith SC et al. Circulation 2006;113:2363-72). These recommendations are based on conflicting evidence about the efficacy of the omega-3 treatment with data derived from single randomized trials or non-randomized studies (Smith SC et al. Circulation 2006;113:2363-72). Much effort has been undertaken to elucidate the role of omega-3 fatty acids in the development of cardiovascular disease, but even recent meta-analyses deliver no clear picture; they either favor (Mozaffarian D Jama 2006;296:1885-99) or reject (Hooper L Bmj 2006;332:752-60) the hypothesis of cardioprotective effects of omega-3 FAs.

The objective of the clinical study is to study the effects of fish oil on blood and urinary markers of inflammation and cell stress. By using different permutations of high-dose supplementation of omega-3 and omega-6 fatty acids versus different alimentary omega-3 fish doses and grain alcohol versus different kinds of red wine, this trial will study how omega-3 fatty acids, ethanol and red wine constituents modulate biomarkers of inflammation and cell stress.


Condition Intervention Phase
Healthy
Drug: Fish Oil
Dietary Supplement: Safflower Oil
Dietary Supplement: Ethanol
Dietary Supplement: Omega-3 polyunsaturated fatty acids
Dietary Supplement: Omega-6 polyunsaturated fatty acid
Phase 1

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Effects of Fish Oil and Red Wine on Oxidative Stress Biomarkers: a Randomized Double-blinded Trial on the Modulation of the Eicosanoid and Isoprostane Pathways in Healthy Subjects by Omega-3 Polyunsaturated Fatty Acids and Red Wine.

Resource links provided by NLM:


Further study details as provided by University of Pennsylvania:

Primary Outcome Measures:
  • Urinary isoprostane concentrations [ Time Frame: Hours and days ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Urinary isoprostane concentrations [ Time Frame: Hours and days ] [ Designated as safety issue: No ]
  • Urinary eicosanoid concentrations [ Time Frame: Hours and days ] [ Designated as safety issue: No ]
  • Plasma eicosanoid concentrations [ Time Frame: Hours and days ] [ Designated as safety issue: No ]
  • Blood alcohol concentrations [ Time Frame: Hours and days ] [ Designated as safety issue: No ]
  • Blood fatty acid composition [ Time Frame: Hours to months ] [ Designated as safety issue: No ]
  • Compositional Changes in the Intestinal Microbiome [ Time Frame: Hours and days ] [ Designated as safety issue: No ]
    Collection of stool samples


Other Outcome Measures:
  • Metabolomics, Lipidomics, Transcriptomics [ Time Frame: Baseline, after low and high doses of fish oil supplementation, after high doses of safflower oil supplementation, after ethanol ingestion ] [ Designated as safety issue: No ]
    Exploring potential interactions between polyunsaturated fatty acids and ethanol


Estimated Enrollment: 40
Study Start Date: May 2008
Estimated Study Completion Date: November 2015
Estimated Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fish oil
Omega-3 polyunsaturated fatty acids (n-3 PUFA)
Drug: Fish Oil

Part 1.1: Dose of 9.3 g/day EPA plus 7.5 g/day DHA;

Part 2a (run-in phase): Dose of 1 time 2 capsules per day of Lovaza (total of 1.7 g/d ω-3 PUFA consisting of 930 mg/day EPA and 750 mg/day DHA) for 29±1 days;

Part 2a (study arm): Dose of 3 times 4 capsules per day of Lovaza (total of 10.1 g/d ω-3 PUFA consisting of 5580 mg/day EPA and 4500 mg/day DHA) for 29±1 days

Other Name: LovazaTM (former name: Omacor®)
Dietary Supplement: Ethanol

Part 1 & Part 1.1:

Dose of 0.9 g/kg body weight 98% alcohol solution

Part 2a:

Doses of 0.4 and 0.9 g/kg body weight 98% alcohol solution and a control placebo drinking solution

Part 2b, Part 3:

Doses of 0.4, 0.6 and 0.9 g/kg body weight 98% alcohol solution

Dietary Supplement: Omega-3 polyunsaturated fatty acids

Part 2b:

Alimentary diet delivering ≈ 500 mg/day EPA/DHA,or Alimentary diet delivering ≈ 900-1000 mg/day EPA/DHA, or Alimentary diet delivering ≈ 1500-1800 mg/day EPA/DHA;

Part 3:

Alimentary diet delivering EPA/DHA in a quantity to be determined by Part 2b.

Other Name: n-3 PUFA alimentary supplementation
Active Comparator: Safflower Oil
Omega-6 polyunsaturated fatty acids (n-6 PUFA)
Dietary Supplement: Safflower Oil
Part 2a: (Study Arm): Omega-6 polyunsaturated fatty acids 3 times 4 capsules per day (total of 10.2 g/d ω-6 PUFA) for 29±1 days
Other Name: Omega-6 polyunsaturated fatty acids
Dietary Supplement: Ethanol

Part 1 & Part 1.1:

Dose of 0.9 g/kg body weight 98% alcohol solution

Part 2a:

Doses of 0.4 and 0.9 g/kg body weight 98% alcohol solution and a control placebo drinking solution

Part 2b, Part 3:

Doses of 0.4, 0.6 and 0.9 g/kg body weight 98% alcohol solution

Dietary Supplement: Omega-6 polyunsaturated fatty acid

Part 2b:

Control omega-6 fatty acid alimentary diet (<130 mg/day EPA/DHA)

Other Name: n-6 PUFA alimentary supplementation

Detailed Description:

This clinical study comprises several parts:

Part 1: Single-arm open oral administration of ethanol in n=40 healthy participants.

Part 1.1: Single-arm open oral administration of fish oil capsules and ethanol in n=12 healthy participants.

Part 2a: Randomized double-blind oral administration of fish oil or safflower oil capsules and ethanol in n=44 healthy participants.

Part 2b: Randomized double-blind oral administration of fish foods or control diet and open oral administration of ethanol in n=40 healthy participants.

Part 3: Randomized double-blind oral administration of fish foods or control diet and red wine beverages in n=40 healthy participants.

  Eligibility

Ages Eligible for Study:   21 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Age between 21 - 60,
  • Subjects must be in good health as based on medical history, physical examination, vital signs, and laboratory tests.
  • All Subjects have to adhere to the following criteria:
  • Must be non-smoking volunteers (both male and non-pregnant females) due to a significant influence of smoking and overweight on the outcome measures of lipid peroxidation,
  • Must be of normal weight with a body mass index (BMI) ≤ 25. The correlation between the BMI number and body fatness is fairly strong; however it varies by sex, race, and age. These variations include the following examples: At the same BMI, women tend to have more body fat than men; at the same BMI, older people, on average, tend to have more body fat than younger adults; highly trained athletes may have a high BMI because of increased muscularity rather than increased body fatness; source at http://www.cdc.gov/healthyweight/assessing/bmi/adult_BMI/index.html. Therefore, subjects with a BMI > 25 can be enrolled at the discretion of the PI in writing.
  • Female subjects of child bearing potential must be using a medically acceptable method of contraception (oral contraception, depo-provera injection, IUD, condom with spermicide, diaphragm, cervical cap, progestin implant, abstinence, tubal ligation, oophorectomy, TAH) throughout the entire study period. All female subjects must consent to a urine pregnancy test at screening and just prior to the start of each treatment phase of the study (first study visit, every ethanol administration visit, at first visit of fish oil administration), and during the third week of fish oil administration. All pregnancy tests must be negative at all time points.
  • Male subjects must be surgically sterile and/or agree to use condoms throughout the duration of the study.
  • Persons who consume vitamin supplements are required to undergo a "washout period" of ≥ five weeks without supplement prior to study enrollment (in analogy to Block G, et al. Am J Epidemiol 2002; 156: 274)
  • Urine ethanol assessment indicating abstinence.

Exclusion Criteria:

  • Female subjects who are pregnant or nursing a child.
  • Subjects, who have received an experimental drug, used an experimental medical device within 30 days prior to screening, or who gave a blood donation of ≥ one pint within 8 weeks prior to screening.
  • Subjects with any coagulation, bleeding or blood disorders.
  • Subjects with nutritional inefficiencies in Fe, Zn, Cu, Mg (according to 61)
  • Subjects who are sensitive or allergic to fish, fish oil or fish-containing products.
  • Subjects with any evidence of cancer or history of significant cardiovascular disease (including stroke or TIA), renal, hepatic, respiratory, endocrine, metabolic, hematopoietic or neurological disorder.
  • Subjects with a systolic blood pressure above 160 or a diastolic blood pressure above 95,
  • Subjects with any evidence of GI disorders that could interfere with fat absorption
  • Subjects with an intention to lose weight during their participation in the trial
  • Subjects with any abnormal laboratory value or physical finding that according to the investigator may interfere with interpretation of the study results, be indicative of an underlying disease state, or compromise the safety of a potential subject. Subjects who have had a history of drug or alcohol abuse within the last 6 months.
  • Carbohydrate-deficient transferrin > 6% indicating chronic alcohol abuse
  • Complete abstinence from alcohol
  • Intake of more than three alcoholic drinks per day
  • Subjects with a history of cancer, including skin cancer
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00682318

Contacts
Contact: Lavenia Banas, CRN 215.662.4652 banas@itmat.upenn.edu
Contact: Carsten Skarke, M.D. 215-746-8330 cskarke@mail.med.upenn.edu

Locations
United States, Pennsylvania
Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Lavenia Banas, CRN    215-662-4652    banas@itmat.upenn.edu   
Contact: Carsten Skarke, M.D.    215-746-8330    cskarke@mail.med.upenn.edu   
Principal Investigator: Garret A FitzGerald, M.D.         
Principal Investigator: Carsten Skarke, M.D.         
Sponsors and Collaborators
Carsten Skarke
American Heart Association
Investigators
Principal Investigator: Garret A FitzGerald, M.D. Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
Principal Investigator: Carsten Skarke, M.D. Institute for Translational Medicine and Therapeutics (ITMAT), University of Pennsylvania School of Medicine
  More Information

No publications provided

Responsible Party: Carsten Skarke, Research Assistant Professor of Medicine in Pharmacology, University of Pennsylvania
ClinicalTrials.gov Identifier: NCT00682318     History of Changes
Other Study ID Numbers: 807069
Study First Received: May 16, 2008
Last Updated: February 5, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Pennsylvania:
Fish oil
red wine
alcohol
oxidative stress
Healthy volunteers

ClinicalTrials.gov processed this record on August 28, 2014