AgingNCT00579774
Effects of Glycoxidative Stress on Human Aging
A study testing Low AGE Diet and Regular Diet in people with Aging, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Aging
- What is being tested?
- Low AGE Diet and Regular Diet
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 438 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2007to Oct 2011
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult subjects of any gender or race between the ages of 18 and 35 or older than 60 years
Who cannot join
- 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
Show all 9Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Mount Sinai School of Medicine
New York, New York, 10029
About this study
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.
Read the 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).
- Conditions
- Aging
- Being tested
- Low AGE Diet, Regular Diet
- Keywords
- Aging, oxidative stress, glycoxidative stress, glycation, inflammation, nutrition, low AGE intake, dietary AGEs
- Medical subject headings
- Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Low AGE DietOther
Diet
Regular DietOther
Diet
| Study group | Role | What they receive |
|---|---|---|
| 1 - Low AGE Diet | Experimental | Low Age Diet Receives: Other: Low AGE Diet |
| 2 - Regular Diet | Active comparator | Regular Diet Receives: Other: Regular Diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Levels of AGE
Measured: Monthly
Secondary outcomes (1)
Side Effect Measurement
Measured: Monthly
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2007 (estimated)
- Study startJan 2007
- Primary completionOct 2009
- Study completionOct 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for AgingStudies of the same condition, open and under way.
- More trials run by Icahn School of Medicine at Mount SinaiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 438 participants (actual)
Sponsor and investigators
- Lead sponsor
- Icahn School of Medicine at Mount Sinai
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Responsible party
- Sponsor
- Investigators
- Helen Vlassara, MD, Principal investigator, Icahn School of Medicine at Mount Sinai
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00579774
- Sponsor's protocol ID
- GCO 03-0116
- Other IDs
- 5R37AG023188
- Status last verified
- Apr 2014
- First submitted
- 19 Dec 2007
- Last updated
- 9 Apr 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Cai W, Uribarri J, Zhu L, Chen X, Swamy S, Zhao Z, Grosjean F, Simonaro C, Kuchel GA, Schnaider-Beeri M, Woodward M, Striker GE, Vlassara H. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940-5. doi: 10.1073/pnas.1316013111. Epub 2014 Feb 24.
PubMed 24567379Uribarri J, Cai W, Pyzik R, Goodman S, Chen X, Zhu L, Ramdas M, Striker GE, Vlassara H. Suppression of native defense mechanisms, SIRT1 and PPARgamma, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases. Amino Acids. 2014 Feb;46(2):301-9. doi: 10.1007/s00726-013-1502-4. Epub 2013 May 1.
PubMed 23636469Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 2011 Jul;34(7):1610-6. doi: 10.2337/dc11-0091.
PubMed 21709297Beeri MS, Moshier E, Schmeidler J, Godbold J, Uribarri J, Reddy S, Sano M, Grossman HT, Cai W, Vlassara H, Silverman JM. Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev. 2011 Nov-Dec;132(11-12):583-7. doi: 10.1016/j.mad.2011.10.007. Epub 2011 Nov 3.
PubMed 22079406Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J. Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE receptor-1. J Clin Endocrinol Metab. 2009 Nov;94(11):4483-91. doi: 10.1210/jc.2009-0089. Epub 2009 Oct 9.
PubMed 19820033Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. doi: 10.1016/j.jada.2010.03.018.
PubMed 20497781Vlassara H, Uribarri J, Ferrucci L, Cai W, Torreggiani M, Post JB, Zheng F, Striker GE. Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons. Semin Nephrol. 2009 Nov;29(6):594-603. doi: 10.1016/j.semnephrol.2009.07.013.
PubMed 20006791
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Glycoxidative Stress on Human Aging
- ClinicalTrials.gov ID
- NCT00579774
- Acronym / sponsor ID
- GCO 03-0116
- Conditions
- Aging
- Keywords
- Aging, oxidative stress, glycoxidative stress, glycation, inflammation, nutrition, low AGE intake, dietary AGEs
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 438 participants (actual)
- Lead sponsor
- Icahn School of Medicine at Mount SinaiUniversity, hospital or other
- Collaborators
- National Institute on Aging (NIA)
- Study start
- Jan 2007
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2011 (actual)
- First posted
- 24 Dec 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 - Low AGE Diet | Experimental | Other: Low AGE DietLow Age Diet |
| 2 - Regular Diet | Active comparator | Other: Regular DietRegular Diet |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Adult subjects of any gender or race between the ages of 18 and 35 or older than 60 years
Key exclusion criteria (9 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Low AGE DietDiet | Other | 1 - Low AGE Diet |
| Regular DietDiet | Other | 2 - Regular Diet |
Primary outcome
Levels of AGE
Time frame: Monthly
1 secondary outcome
Side Effect Measurement
Time frame: Monthly
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2014.
- Results publication: PubMed 24567379Cai W, Uribarri J, Zhu L, Chen X, Swamy S, Zhao Z, Grosjean F, Simonaro C, Kuchel GA, Schnaider-Beeri M, Woodward M, Striker GE, Vlassara H. Oral glycotoxins are a modifiable cause of dementia and the metabolic syndrome in mice and humans. Proc Natl Acad Sci U S A. 2014 Apr 1;111(13):4940-5. doi: 10.1073/pnas.1316013111. Epub 2014 Feb 24.
- Results publication: PubMed 23636469Uribarri J, Cai W, Pyzik R, Goodman S, Chen X, Zhu L, Ramdas M, Striker GE, Vlassara H. Suppression of native defense mechanisms, SIRT1 and PPARgamma, by dietary glycoxidants precedes disease in adult humans; relevance to lifestyle-engendered chronic diseases. Amino Acids. 2014 Feb;46(2):301-9. doi: 10.1007/s00726-013-1502-4. Epub 2013 May 1.
- Results publication: PubMed 21709297Uribarri J, Cai W, Ramdas M, Goodman S, Pyzik R, Chen X, Zhu L, Striker GE, Vlassara H. Restriction of advanced glycation end products improves insulin resistance in human type 2 diabetes: potential role of AGER1 and SIRT1. Diabetes Care. 2011 Jul;34(7):1610-6. doi: 10.2337/dc11-0091.
- Results publication: PubMed 22079406Beeri MS, Moshier E, Schmeidler J, Godbold J, Uribarri J, Reddy S, Sano M, Grossman HT, Cai W, Vlassara H, Silverman JM. Serum concentration of an inflammatory glycotoxin, methylglyoxal, is associated with increased cognitive decline in elderly individuals. Mech Ageing Dev. 2011 Nov-Dec;132(11-12):583-7. doi: 10.1016/j.mad.2011.10.007. Epub 2011 Nov 3.
- Results publication: PubMed 19820033Vlassara H, Cai W, Goodman S, Pyzik R, Yong A, Chen X, Zhu L, Neade T, Beeri M, Silverman JM, Ferrucci L, Tansman L, Striker GE, Uribarri J. Protection against loss of innate defenses in adulthood by low advanced glycation end products (AGE) intake: role of the antiinflammatory AGE receptor-1. J Clin Endocrinol Metab. 2009 Nov;94(11):4483-91. doi: 10.1210/jc.2009-0089. Epub 2009 Oct 9.
- Results publication: PubMed 20497781Uribarri J, Woodruff S, Goodman S, Cai W, Chen X, Pyzik R, Yong A, Striker GE, Vlassara H. Advanced glycation end products in foods and a practical guide to their reduction in the diet. J Am Diet Assoc. 2010 Jun;110(6):911-16.e12. doi: 10.1016/j.jada.2010.03.018.
- Results publication: PubMed 20006791Vlassara H, Uribarri J, Ferrucci L, Cai W, Torreggiani M, Post JB, Zheng F, Striker GE. Identifying advanced glycation end products as a major source of oxidants in aging: implications for the management and/or prevention of reduced renal function in elderly persons. Semin Nephrol. 2009 Nov;29(6):594-603. doi: 10.1016/j.semnephrol.2009.07.013.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Helen Vlassara, MD principal investigator
Icahn School of Medicine at Mount Sinai
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Low AGE Diet and Regular Diet in people with Aging, run by Icahn School of Medicine at Mount Sinai at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Levels of AGE (time frame: Monthly). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00579774, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2014.