Clinical trial NCT02739971: Dietary Reduction of AGEs to Prevent Cognitive Decline in Elderly Diabetics
Official title: Dietary Reduction of Advanced Glycation End Products to Prevent Cognitive Decline in Elderly Diabetics - a Randomized Pilot Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cognitive Decline
Aging
Type 2 Diabetes
Lead sponsor: Sheba Medical Center
Sponsor class: OTHER_GOV
Collaborators: name: Hebrew University of Jerusalem
First posted: 2016-04-15
Enrollment: 75
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: A randomized pilot trial
Primary purpose: PREVENTION

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.


Eligibility criteria: * 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

Primary outcomes:
measure: Change from baseline in AGEs markers in serum (carboxymethyl lysine, CML and Methylglyoxal ,MG ) at 6 months
timeFrame: 6 months
Secondary outcomes:
measure: recruiting rate assessment
timeFrame: 2 years of total recruitment
measure: retention rate to the diet
timeFrame: 6 months
Other outcomes:
measure: The influence of AGE reduction on cognition
timeFrame: 6 months
measure: The influence of AGE reduction on cerebral blood flow-measured with arterial spin labeling MRI (ASL-MRI)
timeFrame: 6 months
measure: Change in microbial diversity and composition of fecal microbiome following AGE reduction in diet
timeFrame: 6 months
Locations:
city: Ramat Gan
country: Israel
facility: Joseph Sagol Neuroscience center, Sheba Medical Center
Study officials:
affiliation: The Joseph Sagol Neuroscience Center
name: Michal Schnaider Beeri, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hebrew University of Jerusalem
name: Aron M Troen, DPhil
role: PRINCIPAL_INVESTIGATOR
affiliation: The Joseph Sagol Neuroscience Center
name: Ramit Ravona Springer, MD
role: STUDY_DIRECTOR
References:
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.
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.
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 Abeta deposition in an Alzheimer mouse model. Aging Cell. 2016 Apr;15(2):309-16. doi: 10.1111/acel.12436. Epub 2016 Jan 19.
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.
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.
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. doi: 10.1001/archneur.64.4.570.
citation: 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.
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.
citation: 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.
citation: 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.