Effect of a Low Advanced Glycation End Products (AGE) Diet in the Metabolic Syndrome

Metabolic Syndrome Clinical Trial

Official title:

Effects of Glycooxidative Stress on Human Aging- Study #3

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01363141
• Other study ID #: GCO 03-0116-3
• Secondary ID: 2RO1DK091231-07A
• Status: Completed
• Phase: N/A
• First received: May 27, 2011
• Last updated: May 6, 2015
• Start date: December 2010
• Est. completion date: December 2014

Study information

• Verified date: May 2015
• Source: Icahn School of Medicine at Mount Sinai
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators have previously demonstrated that Advanced Glycation End products (AGEs) are associated with several chronic diseases in humans and that blood AGE levels can be significantly reduced by simply changing the way food is cooked.

This is an interventional-randomized study in which we are trying to determine whether a diet low in AGE followed for 1 year can effectively reduce circulating AGE levels as well as markers of the metabolic syndrome in a group of patients with these abnormal markers.

Description:

The metabolic syndrome (MetSyn), a well-defined cluster of pathogenic conditions, includes glucose intolerance, insulin resistance (pre-diabetes), hypertension, abdominal obesity, and dyslipidemia. The MetSyn has a strong inflammatory component and raises the risk for cardiovascular disease (CVD) by five-fold and of diabetes by two fold in aging. Although, excessive caloric intake, i.e. "over nutrition" is known to be involved in developing the MetSyn, the actual causative agents of MetSyn in human nutrition have not been determined.

The investigators have previously shown that Advanced Glycation End products (AGEs) can induce oxidant stress and inflammatory responses and modulate insulin signaling in animal models and more recently in humans. These studies separated the effects of "over-nutrition" from the pro-inflammatory effects of AGEs, a factor not previously considered. These data support our hypothesis that AGE-restriction could be an important intervention in the MetSyn in aging.

The investigators would like to demonstrate that this safe, practical and economical intervention can arrest the progression of three major "epidemics" of aging: diabetes, obesity, and vascular disease associated with the metabolic syndrome. This simple intervention could have significant health and economic implications.

Our hypothesis is that dietary AGE restriction can reverse several cardinal manifestation of the MetSyn, specifically insulin resistance, abdominal obesity and cardiovascular disease.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 383
• Est. completion date: December 2014
• Est. primary completion date: December 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 50 Years and older

Eligibility

Inclusion Criteria:

• Non-smoking adult subjects with at least three of the following five characteristics of the metabolic syndrome (MetSyn):

• Waist circumference:

Men: > 102 cm Women: > 88 cm

• Blood pressure: > 130/85 mm Hg (or use of anti-Blood Pressure medication)

• HDL-cholesterol:

Men: < 40 mg/dL Women: < 50 mg/dL

• Triglycerides: > 150 mg/dL (or use of medications for high triglycerides such as fibrates or nicotinic acid)

• Fasting blood sugar > 100 mg/dl (or use of metformin), but a Glycated hemoglobin (HbA1c) <6.5%

• Any gender and race 50 years old or above

• Dietary AGE intake > 12 AGE Eq/day

(Before randomization all participants will be screened with a 3-day food record and 7-day food frequency questionnaire (AGE Quick Score) to determine their average spontaneous daily intake of AGEs. Only those subjects whose daily intake is > 12 AGE Eq/day will participate in the study.)

Exclusion Criteria:

• Diagnosis of diabetes (HbA1C > 6.5 %)

• Glomerular Filtration Rate (GFR) less than 60 ml/min

• Any major cardiovascular event within the preceding 3 months

• Inability to understand or unwillingness to follow study diets

• Any unstable medical condition requiring medication adjustment or treatment within the preceding 3 months

• Any severe illness with an expected participant survival less than 1 year

• Diagnosis of HIV

• Currently receiving treatment for any inflammatory condition

• Currently receiving cancer treatment, such as radiation, chemotherapy, hormone therapy, or stem cell transplant

• Currently participating in any other research study requiring a special diet, medications, supplements or other lifestyle change

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X

Intervention

Other:
• Regular AGE Diet
Regular AGE Diet
• Low AGE Diet
One year reduction in dietary AGE intake.

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai	New York	New York

Sponsors (2)

Lead Sponsor	Collaborator
Icahn School of Medicine at Mount Sinai	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Country where clinical trial is conducted

United States, 

References & Publications (7)

4. Vlassara, H., Striker, G.E Advanced Glycation Endproducts in Diabetes - A Paradigm Shift", Nature-Endocrinology, 2011, in press.

6. Vlassara, H. and Striker, G.E. (2010) Intake of advanced glycation endproducts; Role in the development of diabetic complications. In: Principles of Diabetes Mellitus, 2nd Edition, L. Poretsky, Ed., Springer Publications.

7. Vlassara, H, Striker, G.E. The Role of AGEs in the Etiology of Insulin Resistance and Diabetes; US-Endocrinology (2011).

Mericq V, Piccardo C, Cai W, Chen X, Zhu L, Striker GE, Vlassara H, Uribarri J. Maternally transmitted and food-derived glycotoxins: a factor preconditioning the young to diabetes? Diabetes Care. 2010 Oct;33(10):2232-7. doi: 10.2337/dc10-1058. Epub 2010 Jul 13. — View Citation

Striker GE. Beyond phosphate binding: the effect of binder therapy on novel biomarkers may have clinical implications for the management of chronic kidney disease patients. Kidney Int Suppl. 2009 Dec;(114):S1-2. doi: 10.1038/ki.2009.400. — View Citation

Uribarri 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. — View Citation

Uribarri 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Blood Glucose and Insulin levels in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve insulin resistance in subjects with metabolic syndrome. Insulin resistance will be assessed by measuring simultaneously blood glucose and insulin levels in the fasting state and during an oral glucose tolerance test.	baseline	No
Primary	Change in Blood Glucose and Insulin levels in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve insulin resistance in subjects with metabolic syndrome. Insulin resistance will be assessed by measuring simultaneously blood glucose and insulin levels in the fasting state and during an oral glucose tolerance test.	after 1 year	No
Secondary	Change in abdominal obesity in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness.	baseline	No
Secondary	Change in abdominal obesity in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness.	after 1 year	No
Secondary	Change in markers of cardiovascular disease in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness.	baseline	No
Secondary	Change in markers of cardiovascular disease in 1 year as compared to baseline	To test whether prolonged (1 year) dietary AGE restriction, while maintaining caloric intake, can improve abdominal obesity and markers of cardiovascular disease in subjects with metabolic syndrome. Abdominal obesity will be measured by both waist circumference and MRI. CVD markers will be measured both in the circulation as well as by MRI estimate of carotid artery intima/media thickness.	after 1 year	No

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