Dietary Reduction of AGEs to Prevent Cognitive Decline in Elderly Diabetics
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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N/A |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Low AGEs diet 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
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
Behavioral: Standard of care dietary guidance for Type 2 diabetes
Oral and written instructions for standard of care dietary guidance for type 2 diabetes
|
| Placebo Comparator: Standard of care dietary guidance 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
Oral and written instructions for standard of care dietary guidance for type 2 diabetes
|
Outcome Measures
Primary Outcome Measures
- Change from baseline in AGEs markers in serum (carboxymethyl lysine, CML and Methylglyoxal ,MG ) at 6 months [6 months]
Blood draws before and at the end of the intervention
Secondary Outcome Measures
- recruiting rate assessment [2 years of total recruitment]
calculate the eligible subjects from those attended screening visit
- retention rate to the diet [6 months]
to report the retention rate
Other Outcome Measures
- The influence of AGE reduction on cognition [6 months]
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)
- The influence of AGE reduction on cerebral blood flow-measured with arterial spin labeling MRI (ASL-MRI) [6 months]
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)
- Change in microbial diversity and composition of fecal microbiome following AGE reduction in diet [6 months]
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.
Eligibility Criteria
Criteria
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Above the age 65
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T2D diagnosis
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no dementia (i.e MCI or cognitively normal )
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Not receiving cholinesterase inhibitors
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No other neurological (e.g. stroke, Parkinson's disease) or psychiatric conditions (e.g. schizophrenia, depression) that may affect cognition
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Dietary AGE levels > 13kU
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Not participating in another clinical trial
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An informant that is willing to actively support the participant throughout the study
Exclusion Criteria:
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Dementia
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Stroke
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Other major neuropsychiatric condition that might affect cognition
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Joseph Sagol Neuroscience center, Sheba Medical Center | Ramat Gan | Israel |
Sponsors and Collaborators
- Sheba Medical Center
- Hebrew University of Jerusalem
Investigators
- Principal Investigator: Michal Schnaider Beeri, PhD, The Joseph Sagol Neuroscience Center
- Principal Investigator: Aron M Troen, DPhil, Hebrew University of Jerusalem
- Study Director: Ramit Ravona Springer, MD, The Joseph Sagol Neuroscience Center
Study Documents (Full-Text)
None provided.More Information
Publications
- 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.
- 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.
- 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 Aβ deposition in an Alzheimer mouse model. Aging Cell. 2016 Apr;15(2):309-16. doi: 10.1111/acel.12436. Epub 2016 Jan 19.
- 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.
- 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.
- 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.
- 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.
- 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.
- SHEBA-15-2206-IG-CTIL