Dietary Reduction of AGEs to Prevent Cognitive Decline in Elderly Diabetics

NCT02739971 | Completed

• 1 other identifier: SHEBA-15-2206-IG-CTIL
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

Basic science and observational human studies suggest that high conentrations of circulating Advanced Glycation End-products (AGEs) may promote cognitive decline in older adults. The purpose of this pilot study is to test the methodology and feasibility of a dietary intervention to lower AGEs in elderly diabetics in order to lay the foundations for a future fully powered randomized clinical trial (RCT).To this end, the present study is focused on recruitment strategies, adherence to an innovative intervention in older adults and study methods. An exploratory aim will be the effect of the intervention on cognition and cerebral blood flow in order to obtain necessary data to estimate effect-size for a future fully-powered RCT.

Conditions

Cognitive Decline; Aging; Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Change from baseline in AGEs markers in serum (carboxymethyl lysine, CML and Methylglyoxal ,MG ) at 6 months

  Blood draws before and at the end of the intervention

  6 months

Secondary Outcomes (2)

• recruiting rate assessment

  2 years of total recruitment

• retention rate to the diet

  6 months

Other Outcomes (3)

• The influence of AGE reduction on cognition

  6 months

• The influence of AGE reduction on cerebral blood flow-measured with arterial spin labeling MRI (ASL-MRI)

  6 months

• Change in microbial diversity and composition of fecal microbiome following AGE reduction in diet

  6 months

Study Arms (2)

Low AGEs diet

ACTIVE COMPARATOR

Participants randomized to this arm will receive active instruction on reducing dietary AGEs intake, in addition to standard of care dietary guidance for type 2 diabetes.

Behavioral: Low AGEs diet; Behavioral: Standard of care dietary guidance for Type 2 diabetes

Standard of care dietary guidance

PLACEBO COMPARATOR

Participants randomized to this arm will only recieve standard of care dietary guidance for type 2 diabetes.

Behavioral: Standard of care dietary guidance for Type 2 diabetes

Interventions

Low AGEs diet BEHAVIORAL

Oral and written instructions on how to reduce AGEs in diet, mainly by changing cooking methods in addition to standard of care dietary guidance for type 2 diabetes

Low AGEs diet

Standard of care dietary guidance for Type 2 diabetes BEHAVIORAL

Oral and written instructions for standard of care dietary guidance for type 2 diabetes

Low AGEs diet; Standard of care dietary guidance

Eligibility Criteria

• Age: 65 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may not qualify if:

• Dementia
• Stroke
• Other major neuropsychiatric condition that might affect cognition

Sponsors & Collaborators

• Sheba Medical Center: lead
• Hebrew University of Jerusalem: collaborator

Study Sites (1)

Joseph Sagol Neuroscience center, Sheba Medical Center

Ramat Gan, Israel

Location

Related Publications (10)

• 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.

  PMID: 20497781 BACKGROUND

• 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.

  PMID: 24567379 BACKGROUND

• Lubitz I, Ricny J, Atrakchi-Baranes D, Shemesh C, Kravitz E, Liraz-Zaltsman S, Maksin-Matveev A, Cooper I, Leibowitz A, Uribarri J, Schmeidler J, Cai W, Kristofikova Z, Ripova D, LeRoith D, Schnaider-Beeri M. High dietary advanced glycation end products are associated with poorer spatial learning and accelerated Abeta deposition in an Alzheimer mouse model. Aging Cell. 2016 Apr;15(2):309-16. doi: 10.1111/acel.12436. Epub 2016 Jan 19.

  PMID: 26781037 BACKGROUND

• 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.

  PMID: 21709297 BACKGROUND

• Ravona-Springer R, Luo X, Schmeidler J, Wysocki M, Lesser G, Rapp M, Dahlman K, Grossman H, Haroutunian V, Schnaider Beeri M. Diabetes is associated with increased rate of cognitive decline in questionably demented elderly. Dement Geriatr Cogn Disord. 2010;29(1):68-74. doi: 10.1159/000265552. Epub 2010 Jan 30.

  PMID: 20130405 BACKGROUND

• Luchsinger JA, Reitz C, Patel B, Tang MX, Manly JJ, Mayeux R. Relation of diabetes to mild cognitive impairment. Arch Neurol. 2007 Apr;64(4):570-5. doi: 10.1001/archneur.64.4.570.

  PMID: 17420320 BACKGROUND

• Beeri 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.

  PMID: 22079406 BACKGROUND

• West RK, Moshier E, Lubitz I, Schmeidler J, Godbold J, Cai W, Uribarri J, Vlassara H, Silverman JM, Beeri MS. Dietary advanced glycation end products are associated with decline in memory in young elderly. Mech Ageing Dev. 2014 Sep;140:10-2. doi: 10.1016/j.mad.2014.07.001. Epub 2014 Jul 15.

  PMID: 25037023 BACKGROUND

• Lotan R, Ganmore I, Livny A, Shelly S, Zacharia M, Uribarri J, Beisswenger P, Cai W, Schnaider Beeri M, Troen AM. Design and Feasibility of a Randomized Controlled Pilot Trial to Reduce Exposure and Cognitive Risk Associated With Advanced Glycation End Products in Older Adults With Type 2 Diabetes. Front Nutr. 2021 Feb 15;8:614149. doi: 10.3389/fnut.2021.614149. eCollection 2021.

  PMID: 33659267 DERIVED

• Lotan R, Ganmore I, Shelly S, Zacharia M, Uribarri J, Beisswenger P, Cai W, Troen AM, Schnaider Beeri M. Long Term Dietary Restriction of Advanced Glycation End-Products (AGEs) in Older Adults with Type 2 Diabetes Is Feasible and Efficacious-Results from a Pilot RCT. Nutrients. 2020 Oct 15;12(10):3143. doi: 10.3390/nu12103143.

  PMID: 33076217 DERIVED

MeSH Terms

Conditions

Cognitive Dysfunction; Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Officials

• Michal Schnaider Beeri, PhD

  The Joseph Sagol Neuroscience Center

  PRINCIPAL INVESTIGATOR

• Aron M Troen, DPhil

  Hebrew University of Jerusalem

  PRINCIPAL INVESTIGATOR

• Ramit Ravona Springer, MD

  The Joseph Sagol Neuroscience Center

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The participants and study dietitian can not be blind to the assigned dietary intervention. However, the clinical testing and all data analysis are carried out blind to the intervention.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principle investigator

Model Details: A randomized pilot trial

Study Record Dates

• First Submitted: April 5, 2016
• First Posted: April 15, 2016
• Study Start: June 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: March 23, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will not share

Locations

IL (1)