Anti-inflammatory and Antioxidant Effects of Resveratrol on Healthy Adults.

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Simona Bo, University of Turin, Italy
ClinicalTrials.gov Identifier:
NCT01492114
First received: December 12, 2011
Last updated: July 6, 2012
Last verified: July 2012
  Purpose

This research will investigate the hypothesis that resveratrol when given orally to healthy adult smokers induces a decrease in the inflammatory and oxidative mediators which characterize the low-grade systemic inflammatory state and the oxidants-antioxidants imbalance of tobacco users.


Condition Intervention Phase
Chronic Subclinic Inflammation
Redox Status
Dietary Supplement: Resveratrol
Dietary Supplement: resveratrol
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Crossover Assignment
Masking: Double Blind (Subject, Caregiver)
Primary Purpose: Prevention
Official Title: Double-blind Cross-over Randomised Controlled Trial on the Anti-inflammatory and Antioxidant Effects of Resveratrol on Healthy Adults.

Resource links provided by NLM:


Further study details as provided by University of Turin, Italy:

Primary Outcome Measures:
  • C-reactive protein [ Time Frame: At baseline and every 30 days for three months ] [ Designated as safety issue: No ]
    To evaluate before-after changes in circulating concentrations of C-reactive protein (CRP), an inflammation marker, in smokers submitted to resveratrol supplementation when compared to smokers treated with placebo


Secondary Outcome Measures:
  • TAS (total antioxidant status) [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: TAS (total antioxidant status.


  • 4-hydroxynonenal [ Time Frame: At baseline and after 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: 4-hydroxynonenal


  • nitrotyrosine [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: nitrotyrosine.


  • endothelial nitric oxide synthase (eNOS)-polymorphism [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: endothelial nitric oxide synthase (eNOS)-polymorphism


  • superoxide dismutase (SOD2)-polymorphism [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: superoxide dismutase (SOD2)-polymorphism.


  • catalase-polymorphism [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -markers of oxidative stress: catalase-polymorphism


  • interleukin-6 [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -other markers of inflammation: interleukin-6.


  • pentraxin 3 [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -other markers of inflammation: pentraxin 3.


  • tumor necrosis factor-α [ Time Frame: At baseline and every 30-days for three months ] [ Designated as safety issue: No ]

    To evaluate before-after changes in circulating fasting concentrations of the following parameters:

    -other markers of inflammation: tumor necrosis factor-α.



Enrollment: 40
Study Start Date: July 2011
Study Completion Date: March 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Resveratrol first
Subjects in the group "resveratrol first" will be submitted to: 30 days of treatment with Transmax (resveratrol, 500 mg, Biotivia Bioceuticals LLC), one tablet/day in the morning at fasting; then to 30 days of wash-out (no supplementation), and then to 30 days of treatment with placebo (one tablet/day in the morning at fasting).
Dietary Supplement: Resveratrol
Subjects in the group "resvetarol first" will be submitted to: 30 days of treatment with Transmax (resveratrol, 500 mg, Biotivia Bioceuticals LLC), one tablet/day in the morning at fasting; then to 30 days of wash-out (no supplementation), and then to 30 days of treatment with placebo (one tablet/day in the morning at fasting).
Active Comparator: Placebo first
Subjects in the group "Placebo first" will be submitted to: 30 days of treatment with placebo, one tablet/day in the morning at fasting; than to 30 days of wash-out (no supplementation), and then to 30 days of treatment with Transmax (resveratrol, 500 mg) (one tablet/day in the morning at fasting).
Dietary Supplement: resveratrol
Subjects in the group "Placebo first" will be submitted to: 30 days of treatment with placebo, one tablet/day in the morning at fasting; than to 30 days of wash-out (no supplementation), and then to 30 days of treatment with Transmax (resveratrol, 500 mg) (one tablet/day in the morning at fasting).

Detailed Description:

The effect of resveratrol in humans is still not well defined. The number of studies on resveratrol has increased extraordinarily since 1997, when its anticancer effect has been reported. However, most of these studies are in-vitro or animal studies. Preclinical observations in humans suggest that resveratrol is safe and has potential in the treatment of obesity and insulin resistance in humans.

In particular, it improves insulin sensitivity, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway. Studies on toxicity of resveratrol in humans demonstrated that this compound is well tolerated and no adverse effect has been found with higher dosage (5g/day). Resveratrol is available to people over-the-counter in health food stores and the internet as a dietary supplement. In humans, resveratrol is efficiently absorbed after oral administration; however, rapid phase II metabolism drastically limits its plasma bio-availability. The high concentrations of resveratrol in colorectal tissues, in excess of that required for activity in vitro, supports the colon as a target organ. The efficacy of resveratrol in other tissues may be largely dependent on whether its metabolites have significant activity or are able to regenerate resveratrol either locally or systemically (e.g. some metabolites, mainly sulfate-conjugated resveratrol, show biological effects in cellular models).

There are only a few studies evaluating the anti-inflammatory properties of resveratrol in humans. An extract of Polygonum Cuspidatum containing resveratrol given for 6-weeks to 10 healthy subjects was able to significantly suppress plasma concentrations of inflammatory cytokines (C-reactive protein, interleukin-6, tumor necrosis factor-α). Similarly, a nutritional supplement containing resveratrol plays an acute antioxidant and antiinflammatory effects in the postprandial state after a high-fat, high-carbohydrate meal in 10 healthy females.

The anti-inflammatory and antioxidant effects of resveratrol may be particularly interesting for smokers. Resveratrol increases the NO bioavailability and the inhibition of cyclooxygenase and 5-lipoxygenase activity of Cox-1 and it prevents the vascular leucocyte migration into damaged organs by decreasing the expression of endothelial vascular adhesion molecules and of pro-inflammatory genes. The inflammatory responses induced by oxidized LDL (low-density lipoproteins) are partially avoided by the addition of reveratrol and the authors concluded that it could affect vascular inflammation or/and injury not only as antioxidant, but also as modulator of inflammatory redox signalling pathways.

However, there are currently no published demonstrations of therapeutic or protective effects of resveratrol in appropriately designed clinical trials.

  Eligibility

Ages Eligible for Study:   20 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • age 20-50 years
  • actual smoking (≥5 cigarettes/die)
  • mean alcohol consumption <30g/day
  • absence of known hyperglycaemia, hypertension, cardiovascular disease, impaired renal function, liver disease, or any other systemic conditions -no use of any drug -oestrogen excluded-
  • not being on a particular diet and/or vitamin or other nutrient or integrator supplementation during the least 6-months

Exclusion Criteria:

  • actual pregnancy -known hyperglycaemia, hypertension, cardiovascular disease, impaired renal function, liver disease, or any other systemic chronic or acute conditions, use of any drug -oestrogen excluded-
  • being on a particular diet and/or vitamin or other nutrient or integrator supplementation during the last six months
  • mean alcohol consumption ≥30g/day
  • body mass index (BMI)>30 kg/m2
  • subject unable to give his/her informed consent.
  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: NCT01492114

Locations
Italy
Simona Bo
Turin, Italy, 10126
Sponsors and Collaborators
University of Turin, Italy
Investigators
Principal Investigator: Simona Bo, MD University of Turin
  More Information

No publications provided

Responsible Party: Simona Bo, MD, Department of Internal Medicine, University of Turin, Italy
ClinicalTrials.gov Identifier: NCT01492114     History of Changes
Other Study ID Numbers: sbo2011
Study First Received: December 12, 2011
Last Updated: July 6, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by University of Turin, Italy:
C-reactive protein
Resveratrol
Redox index

Additional relevant MeSH terms:
Resveratrol
Inflammation
Pathologic Processes
Anti-Inflammatory Agents
Antioxidants
Therapeutic Uses
Pharmacologic Actions
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Antirheumatic Agents
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Enzyme Inhibitors
Platelet Aggregation Inhibitors
Hematologic Agents
Antimutagenic Agents
Anticarcinogenic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014