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

Primary Purpose

Metabolic Syndrome

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Regular AGE Diet
Low AGE Diet
Sponsored by
Icahn School of Medicine at Mount Sinai
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metabolic Syndrome focused on measuring Cardiovascular Diseases, Type 2 Diabetes Mellitus, Abdominal Fat, Atherogenic Dyslipidemia, Hypertension, Hyperglycemia, Insulin Resistance, Thrombosis state

Eligibility Criteria

50 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Icahn School of Medicine at Mount Sinai

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Regular AGE Diet

Low AGE Diet

Arm Description

Regular AGE Diet

One year reduction in dietary AGE intake

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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.
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.
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.
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.

Full Information

First Posted
May 27, 2011
Last Updated
May 6, 2015
Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
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1. Study Identification

Unique Protocol Identification Number
NCT01363141
Brief Title
Effect of a Low Advanced Glycation End Products (AGE) Diet in the Metabolic Syndrome
Official Title
Effects of Glycooxidative Stress on Human Aging- Study #3
Study Type
Interventional

2. Study Status

Record Verification Date
May 2015
Overall Recruitment Status
Completed
Study Start Date
December 2010 (undefined)
Primary Completion Date
December 2014 (Actual)
Study Completion Date
December 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Icahn School of Medicine at Mount Sinai
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.
Detailed 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome
Keywords
Cardiovascular Diseases, Type 2 Diabetes Mellitus, Abdominal Fat, Atherogenic Dyslipidemia, Hypertension, Hyperglycemia, Insulin Resistance, Thrombosis state

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Regular AGE Diet
Arm Type
Active Comparator
Arm Description
Regular AGE Diet
Arm Title
Low AGE Diet
Arm Type
Active Comparator
Arm Description
One year reduction in dietary AGE intake
Intervention Type
Other
Intervention Name(s)
Regular AGE Diet
Intervention Description
Regular AGE Diet
Intervention Type
Other
Intervention Name(s)
Low AGE Diet
Intervention Description
One year reduction in dietary AGE intake.
Primary Outcome Measure Information:
Title
Change in Blood Glucose and Insulin levels in 1 year as compared to baseline
Description
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.
Time Frame
baseline
Title
Change in Blood Glucose and Insulin levels in 1 year as compared to baseline
Description
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.
Time Frame
after 1 year
Secondary Outcome Measure Information:
Title
Change in abdominal obesity in 1 year as compared to baseline
Description
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.
Time Frame
baseline
Title
Change in abdominal obesity in 1 year as compared to baseline
Description
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.
Time Frame
after 1 year
Title
Change in markers of cardiovascular disease in 1 year as compared to baseline
Description
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.
Time Frame
baseline
Title
Change in markers of cardiovascular disease in 1 year as compared to baseline
Description
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.
Time Frame
after 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
John C He, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
20497781
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.
Results Reference
background
PubMed Identifier
20628088
Citation
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.
Results Reference
background
PubMed Identifier
21709297
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.
Results Reference
background
PubMed Identifier
24286947
Citation
Vlassara H, Striker GE. Advanced glycation endproducts in diabetes and diabetic complications. Endocrinol Metab Clin North Am. 2013 Dec;42(4):697-719. doi: 10.1016/j.ecl.2013.07.005.
Results Reference
background
PubMed Identifier
19946321
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. No abstract available.
Results Reference
background
Citation
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.
Results Reference
background
Citation
7. Vlassara, H, Striker, G.E. The Role of AGEs in the Etiology of Insulin Resistance and Diabetes; US-Endocrinology (2011).
Results Reference
background
PubMed Identifier
27468708
Citation
Vlassara H, Cai W, Tripp E, Pyzik R, Yee K, Goldberg L, Tansman L, Chen X, Mani V, Fayad ZA, Nadkarni GN, Striker GE, He JC, Uribarri J. Oral AGE restriction ameliorates insulin resistance in obese individuals with the metabolic syndrome: a randomised controlled trial. Diabetologia. 2016 Oct;59(10):2181-92. doi: 10.1007/s00125-016-4053-x. Epub 2016 Jul 29.
Results Reference
derived

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

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