Effects of Glycoxidative Stress on Human Aging - Full Text View

Sponsors and Collaborators:	Mount Sinai School of Medicine National Institute on Aging (NIA)
Information provided by:	Mount Sinai School of Medicine
ClinicalTrials.gov Identifier:	NCT00579774

Purpose

Advanced glycation products or AGEs are a heterogeneous group of molecules formed by exposure of tissue constituents to high levels of reducing sugars, e.g. glucose. The interaction of these compounds with extra- and intra-cellular components may account in part for several conditions related to aging. It has recently been recognized that AGEs are also formed during the preparation of food by heating, are absorbed into the circulation and become largely incorporated into tissue components. Accumulation of these exogenous substances over time may, together with those generated endogenously, contribute to the clinical manifestations and complications of aging.

This is an interventional-randomized study in which we are trying to determine whether a diet low in AGE can effectively reduce circulating AGE levels, with or without altering oxidation or inflammatory markers, in a subset of both young and older subjects , over a period of 4 months. If positive results are obtained, longer-term prospective studies will be designed to determine if this intervention can affect disease outcomes in older age subjects.

The study design is very simple and consists initially of obtaining a dietary history, a blood sample, 24-hour urine collection and, subsequently, of determining the effects of a low-AGE diet for 4 months on the plasma levels of these compounds in a group of healthy subjects.

Condition	Intervention
Aging	Other: Low AGE Diet Other: Regular Diet

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Basic Science, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effects of Glycoxidative Stress on Human Aging

Further study details as provided by Mount Sinai School of Medicine:

Primary Outcome Measures:

Levels of AGE [ Time Frame: Monthly ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Side Effect Measurement [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	80
Study Start Date:	January 2007
Estimated Study Completion Date:	June 2009
Estimated Primary Completion Date:	June 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Low Age Diet	Other: Low AGE Diet Diet
2: Active Comparator Regular Diet	Other: Regular Diet Diet

Detailed Description:

Advancing age is known to be associated with increased oxidant stress (OS), increased prevalence of cardiovascular disease, impaired glucose tolerance, diabetes mellitus, decline of renal function, and accumulation of advanced glycation end products (AGEs). AGEs can lead to activation of transcriptional pathways, excessive proliferative/growth-related phenomena and sustained inflammation and through these different mechanisms may contribute significantly to the clinical complications of aging. Recently, it has become clear that a major source of AGE precursors and OS is the Western diet. The body turnover of AGEs involves specific receptors and is also dependent on renal function.

While experimental work has linked AGE-mediated OS and chronic complications in aging animals, human studies are strikingly lacking. We plan to test the following two hypotheses: 1) older men and women (age > 60 years) who consume standard diets (usually high in AGE content) will have higher serum levels of AGEs in conjunction with higher markers of OS, vascular dysfunction and inflammation when compared with younger subjects (age < 35 but >18 years), and 2) dietary AGE restriction will reduce the serum levels of AGE, markers of OS, vascular dysfunction and inflammation and attenuate the difference between older and younger groups.

Specific aims:

To determine the effect of dietary AGE modification for 4 months on circulating levels of AGEs, markers of oxidative stress, vascular dysfunction, inflammatory mediators and AGE-receptor mechanisms in PBMN in old and young subjects. This will be a randomized study (Study 2).

Eligibility

Ages Eligible for Study:	18 Years to 35 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

Adult subjects of any gender or race between the ages of 18 and 35 or older than 60 years

Exclusion Criteria:

Diagnosis of diabetes (absence of diabetes will be defined as a negative history of diabetes in combination with a HgbA1c < 6% at the time of recruitment)
Any major cardiovascular event (myocardial infarction, stroke, PTCA or coronary artery bypass) within the preceding 3 months
Smokers
Glucocorticoid, anticoagulant (except for aspirin) or antioxidant therapy
Serum creatinine greater than 2 mg/dl
Inability to understand or unwillingness to follow study diets
Any severe illness with an expected patient survival less than 1 year
Patients who have initiated therapy with ACE inhibitors, lipid lowering medications or hormone replacement within the previous 3 months. Patients on stable doses of these medications will be included
Before randomization all subjects will be screened with a 3-day food record to determine their average spontaneous daily intake of AGEs. Only those subjects whose daily intake is on the upper half of normal (greater than 14 AGE Eq/day) will participate in the study. This value of 14 E/day corresponds to the median daily AGE intake estimated in a large number of healthy subjects.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00579774

Contacts

Contact: Jaime Uribarri, MD	212-2412567	Jaime.Uribarri@mountsinai.org
Contact: Angie Yong	212-241-2567	angie.yong@mssm.edu

Locations

United States, New York
Mount Sinai School of Medicine	Recruiting
New York, New York, United States, 10029
Principal Investigator: Helan Vlassara, MD

Sponsors and Collaborators

Mount Sinai School of Medicine

National Institute on Aging (NIA)

Investigators

Principal Investigator:

Helen Vlassara, MD

Mount Sinai School of Medicine

More Information

Responsible Party:	Mount Sinai School of Medicine ( Helen Vlassara )
Study ID Numbers:	03-0116, 5R37AG023188
Study First Received:	December 19, 2007
Last Updated:	December 21, 2007
ClinicalTrials.gov Identifier:	NCT00579774
Health Authority:	United States: Institutional Review Board

Keywords provided by Mount Sinai School of Medicine:

Aging
oxidative stress
glycoxidative stress
glycation

inflammation
nutrition
low AGE intake
dietary AGEs

Study placed in the following topic categories:

Stress
Inflammation

ClinicalTrials.gov processed this record on January 16, 2009