Dietary Reduction of AGEs to Prevent Cognitive Decline in Elderly Diabetics

Type 2 Diabetes Clinical Trial

Official title:

Dietary Reduction of Advanced Glycation End Products to Prevent Cognitive Decline in Elderly Diabetics - a Randomized Pilot Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02739971
• Other study ID #: SHEBA-15-2206-IG-CTIL
• Status: Completed
• Phase: N/A
• Start date: June 2016
• Est. completion date: June 2020

Study information

• Verified date: March 2021
• Source: Sheba Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 75
• Est. completion date: June 2020
• Est. primary completion date: June 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

• Above the age 65

• T2D diagnosis

• no dementia (i.e MCI or cognitively normal )

• Not receiving cholinesterase inhibitors

• No other neurological (e.g. stroke, Parkinson's disease) or psychiatric conditions (e.g. schizophrenia, depression) that may affect cognition

• Dietary AGE levels > 13kU

• Not participating in another clinical trial

• An informant that is willing to actively support the participant throughout the study

Exclusion Criteria:

• Dementia

• Stroke

• Other major neuropsychiatric condition that might affect cognition

Related Conditions & MeSH terms

• Aging
• Cognitive Decline
• Cognitive Dysfunction
• Type 2 Diabetes

Intervention

Behavioral:
• Low AGEs diet
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
• Standard of care dietary guidance for Type 2 diabetes
Oral and written instructions for standard of care dietary guidance for type 2 diabetes

Locations

Country	Name	City	State
Israel	Joseph Sagol Neuroscience center, Sheba Medical Center	Ramat Gan

Sponsors (2)

Lead Sponsor	Collaborator
Sheba Medical Center	Hebrew University of Jerusalem

Country where clinical trial is conducted

Israel, 

References & Publications (8)

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. — View Citation

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. — View Citation

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 Aß deposition in an Alzheimer mouse model. Aging Cell. 2016 Apr;15(2):309-16. doi: 10.1111/acel.12436. Epub 2016 Jan 19. — View Citation

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. — View Citation

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. — 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

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	The influence of AGE reduction on cognition	Changes in cognition using a Z score of global and domain specific (language, attention, memory ) cognition following 6 months of AGEs reduction compared to standard of care (this is an exploratory aim since this is a pilot study)	6 months
Other	The influence of AGE reduction on cerebral blood flow-measured with arterial spin labeling MRI (ASL-MRI)	changes in cerebral blood flow measured with ASL MRI following 6 months of AGEs reduction compared to standard of care ( this is an exploratory aim since this is a pilot study)	6 months
Other	Change in microbial diversity and composition of fecal microbiome following AGE reduction in diet	microbiota composition will be analyzed (eg. the amount and relative proportions of major bacterial genus and species Bifidobacterium, Bacteroides, Lactobaillus, Enterobacteria, Eubacteria,etc. using 16S rRNA profiling ) before and after intervention of AGEs reduction and changes will compared to standard of care arm. This is a descriptive exploratory outcome.	6 months
Primary	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	recruiting rate assessment	calculate the eligible subjects from those attended screening visit	2 years of total recruitment
Secondary	retention rate to the diet	to report the retention rate	6 months