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Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years

Primary Purpose

Vascular System Injuries, Lipid Metabolism Disorders, Endothelial Disfunction

Status
Completed
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
Resveratrol
Caloric restriction
Sponsored by
InCor Heart Institute
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Vascular System Injuries focused on measuring sirtuin, atherosclerosis, longevity, calorie restriction, resveratrol, vascular reactivity

Eligibility Criteria

55 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • clinical history, physical examination and electrocardiogram normal

Exclusion Criteria:

  • premenopausal women (less than 1 year of natural amenorrhea)
  • Body mass index ≥ 35 kg/m2
  • Smoking
  • Severe hypertension (diastolic blood pressure ≥ 110 mmHg)
  • Severe dyslipidemia (triglycerides ≥ 500mg/dL, total cholesterol ≥ 300mg/dL)
  • Diabetes
  • Previous using previous statins or hormone replacement therapy. Other exclusion criteria are: chronic renal failure (serum creatinine ≥ 2.0 mg / dl), hepatic, endocrine, hematologic, respiratory or metabolic clinically significant.

Sites / Locations

  • INCOR - Heart Institute

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

Experimental

Active Comparator

Active Comparator

Arm Label

men with resveratrol

women with resveratrol

men with caloric restriction

women with caloric restriction

Arm Description

12 men will receive a pill with 500mg of resveratrol daily for 30 days

12 women will receive a pill with 500mg of resveratrol daily for 30 days

12 men will follow a 1000 calories per day diet for 30 days

12 women will follow a 1000 calories per day diet for 30 days

Outcomes

Primary Outcome Measures

Direct Evaluation of the Sirtuin 1 Gene Expression
The Sirtuin 1 gene expression was measured by real time PCR in peripheric blood. Unit of measure was arbitrary unit. "Arbitrary unit was relative to the control gene expression (control gene = 1)".
Sirtuin
Sirtuin plasma levels before and 30 days post-treatment

Secondary Outcome Measures

Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - serum HDL, LDL, lipoprotein(a), C reactive protein, glucose.
Influence of the Sirtuin 1 System on Apolipoproteins AI and B.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - apolipoproteins AI and B
Influence of the Sirtuin 1 System on Estradiol
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estradiol
Influence of the Sirtuin 1 System on Platelet Aggregation.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - platelet aggregation by ADP and norepinephrine.
Influence of the Sirtuin 1 System on Biomarkers
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - non-esterified fatty acids, insulin, luteinizing hormone, follicle stimulating hormone.
Influence of the Sirtuin 1 System on Estrone and Norepinephrine.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estrone, norepinephrine.
Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: RAGE gene expression "Arbitrary unit was relative to the control gene expression (control gene = 1)"
Influence of the Sirtuin 1 System on Thromboelastography Clot Formation.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -dynamics of clot formation: clot onset time and clot complet
Influence of the Sirtuin 1 System on Thromboelastography.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - slope of clot formation dynamics
Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography.
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -max elasticity of clot on thromboelastography

Full Information

First Posted
August 14, 2012
Last Updated
March 17, 2016
Sponsor
InCor Heart Institute
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1. Study Identification

Unique Protocol Identification Number
NCT01668836
Brief Title
Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years
Official Title
Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2016
Overall Recruitment Status
Completed
Study Start Date
August 2012 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
InCor Heart Institute

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Women have a natural protection that gives them greater longevity. One hypothesis most commonly used is the estrogen protection in the premenopausal period. However many studies of various forms of hormone replacement therapy proved ineffective in promoting additional protection for women. Thus, it is discussed other ways of protection associated with longevity in women. Of these, the sirtuin system was found in several animal studies to be associated with longevity. This system also showed, through the involvement of several metabolic pathways, an important protection against the process of atherosclerosis. But the activity of this system in humans is unknown and if it is more active in women than in men. The study's main objectives are to analyze this system in healthy 24 women and 24 men aged 55 to 65 years, and their influence on the main metabolic pathways related to longevity and the process of atherosclerosis. The research protocol includes analysis of the influence of sirtuin (SIRT1) in vascular reactivity, lipid profile, antioxidant capacity, markers of inflammation and homeostasis, before and after the interventions with caloric restriction or resveratrol administration. It is expected of this study mechanistic conclusion for longevity and possible clinical applications in the mechanism of atherosclerosis prevention.
Detailed Description
After a washout period of 15 days without medication, men and women will be randomized to the group of calorie restriction or resveratrol so that in 24 individuals (12 women and 12 men) will be given a hypocaloric diet (1000 calories per day) and the remaining 24 individuals (12 women and 12 men), a daily pill of 500mg of resveratrol. In the two moments, after the washout period and before the intervention (baseline) and after 30 days of intervention (final) will evaluate the clinical, laboratory and vascular reactivity of all subjects.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vascular System Injuries, Lipid Metabolism Disorders, Endothelial Disfunction
Keywords
sirtuin, atherosclerosis, longevity, calorie restriction, resveratrol, vascular reactivity

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
48 (Actual)

8. Arms, Groups, and Interventions

Arm Title
men with resveratrol
Arm Type
Experimental
Arm Description
12 men will receive a pill with 500mg of resveratrol daily for 30 days
Arm Title
women with resveratrol
Arm Type
Experimental
Arm Description
12 women will receive a pill with 500mg of resveratrol daily for 30 days
Arm Title
men with caloric restriction
Arm Type
Active Comparator
Arm Description
12 men will follow a 1000 calories per day diet for 30 days
Arm Title
women with caloric restriction
Arm Type
Active Comparator
Arm Description
12 women will follow a 1000 calories per day diet for 30 days
Intervention Type
Drug
Intervention Name(s)
Resveratrol
Intervention Description
1 pill daily containing 500 mg/d of resveratrol for 30 days
Intervention Type
Behavioral
Intervention Name(s)
Caloric restriction
Intervention Description
Diet of 1000kcal per day for 30 days
Primary Outcome Measure Information:
Title
Direct Evaluation of the Sirtuin 1 Gene Expression
Description
The Sirtuin 1 gene expression was measured by real time PCR in peripheric blood. Unit of measure was arbitrary unit. "Arbitrary unit was relative to the control gene expression (control gene = 1)".
Time Frame
30 days post-treatment
Title
Sirtuin
Description
Sirtuin plasma levels before and 30 days post-treatment
Time Frame
30 days post-treatment
Secondary Outcome Measure Information:
Title
Influence of the Sirtuin 1 System on Lipid Profile, Glucose, and C-reactive Protein.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - serum HDL, LDL, lipoprotein(a), C reactive protein, glucose.
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Apolipoproteins AI and B.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - apolipoproteins AI and B
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Estradiol
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estradiol
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Platelet Aggregation.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - platelet aggregation by ADP and norepinephrine.
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Biomarkers
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - non-esterified fatty acids, insulin, luteinizing hormone, follicle stimulating hormone.
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Estrone and Norepinephrine.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - estrone, norepinephrine.
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Receptor for Advanced Glycation End Products (RAGE) Gene Expression
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: RAGE gene expression "Arbitrary unit was relative to the control gene expression (control gene = 1)"
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Thromboelastography Clot Formation.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -dynamics of clot formation: clot onset time and clot complet
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Thromboelastography.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: - slope of clot formation dynamics
Time Frame
30 days post-treatment
Title
Influence of the Sirtuin 1 System on Max Elasticity of Clot on Thromboelastography.
Description
For indirect analysis of the sirtuin 1 system, the following procedures will be done before and after the intervention with caloric restriction or resveratrol administration: -max elasticity of clot on thromboelastography
Time Frame
30 days post-treatment
Other Pre-specified Outcome Measures:
Title
Differences Between Men and Women.
Description
We will also compare women vs men baseline and final data.
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
55 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: clinical history, physical examination and electrocardiogram normal Exclusion Criteria: premenopausal women (less than 1 year of natural amenorrhea) Body mass index ≥ 35 kg/m2 Smoking Severe hypertension (diastolic blood pressure ≥ 110 mmHg) Severe dyslipidemia (triglycerides ≥ 500mg/dL, total cholesterol ≥ 300mg/dL) Diabetes Previous using previous statins or hormone replacement therapy. Other exclusion criteria are: chronic renal failure (serum creatinine ≥ 2.0 mg / dl), hepatic, endocrine, hematologic, respiratory or metabolic clinically significant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antônio de Pádua Mansur, PHD
Organizational Affiliation
InCor Heart Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
INCOR - Heart Institute
City
São Paulo
ZIP/Postal Code
05403-900
Country
Brazil

12. IPD Sharing Statement

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Influence of Caloric Restriction and Resveratrol in the Sirtuin System in Women and Men Aged 55 to 65 Years

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