PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs
Status:
Completed
Trial end date:
2017-12-01
Target enrollment:
Participant gender:
Summary
There is evidence of the association between diabetic microangiopathy and elevated serum
concentrations of advanced glycation end-products (AGEs). AGEs levels are associated with
ingestion of specific foods (baked meats and milk powder); reducing their dietary intake
lowers AGEs concentrations, with beneficial metabolic effects; however threre is still no
evidence of whether this has an impact on microvascular complications of DM. We recently
applied for funding to compare in a RCT the effects of Cholestyramine versus placebo, on
visual electrophysiology. This drug is similar to Sevelamer in structure, both act as
chelators of bile salts, and reduce absorption of dietary AGE, lowering serum levels. However
it is essential to carry out preliminary tests to assess aspects that may imply adjustments
to the proposed protocol, such as: 1) tolerance to the drug 2) short term effect of the drug
versus placebo on serum levels of AGEs 3) effects of the drug versus placebo in levels of fat
soluble vitamins (D and K specifically) 4) intra and interindividual variability of
electrophysiological measurements of vision (ERGMF and optic nerve conduction velocity) 5)
drug versus placebo in electrophysiological measurements of vision (neuroconduction ERGMF and
optic nerve). Objective: The present project is planned as a pilot study, which will clarify
points 1 to 5. Methodology: patients (6 DM2, 25 -50 y) will be assessed through
anthropometry, clinical laboratory tests (creatinine, chemistry profile, lipid profile,
microalbuminuria glycosylated hemoglobin, vitamin B12, 25OH vitamin D and prothrombin),
dietary recalls specifically designed to analyze the regular consumption of AGEs, serum CML
and neuro-ophthalmological study (fundus, ERGMF and optic nerve conduction). Subsequently
each patient will be assigned to treatment with placebo for 3 months and then Cholestyramine
6 g / day for 12 weeks and at the end of each period will be reassessed using the same
methodology. If patients cannot tolerate the drug, they will be assigned to a reduced AGE
diet.
Expected results: Cholestyramine will have side effect similar to placebo (mainly digestive).
The active drug and not placebo will reduce serum levels of AGEs and electrophysiological
parameters of vision at 12 weeks. It is expected that a low AGEs diet in patients who do not
tolerate the drug will also reduce serum CML although to a lesser degree and will also induce
electrophysiologic changes.