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PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs (PREL-AGES)

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ClinicalTrials.gov Identifier: NCT02249897
Recruitment Status : Completed
First Posted : September 26, 2014
Last Update Posted : February 14, 2018
Sponsor:
Collaborator:
Clinica Alemana de Santiago
Information provided by (Responsible Party):
MARIA PIA DE LA MAZA, University of Chile

Brief 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.


Condition or disease Intervention/treatment Phase
DIABETES DIABETIC RETINOPATHY DIABETIC NEUROPATHY Drug: CHOLESTYRAMINE Phase 4

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 7 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention Model Description: Prescription of 6 g oral cholestiramine in 7 patients with type 2 DM, to study changes in neuroophtalmologic variables (electroretinogram and optic nerve conduction)
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: PRELIMINARY EVALUATION OF RETINAL EFFECTS OF PHARMACOLOLOGICAL LOWERING OF SERUM LEVES OF ADVANCED GLYCATION END-PRODUCTS (AGEs) IN TYPE 2 DIABETIC PATIENTS
Actual Study Start Date : January 2015
Actual Primary Completion Date : December 2017
Actual Study Completion Date : December 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: PLACEBO
AFTER COMPLETING THE INITIAL EVALUATION (ANTHROPOMETRY, SERUM BIOCHEMISTRY AND CML LEVELS, FUNDUS, MUTIFOCAL ELECTRORETINOGRAM AND OPTIC NERVE CONDUCTION VELOCITY) PATIENTS WILL RECEIVE ORAL PLACEBO CAPSULES 4 PER EACH MEAL/DAY DURING 12 WEEKS
Drug: CHOLESTYRAMINE
CHOLESTYRAMINE CAPSULES, 6 G/DAY P.O. DURING 12 WEEKS
Other Name: QUESTRAN

Active Comparator: CHOLESTIRAMINE
AFTER COMPLETING THE CONTROL PERIOD (PLACEBO CAPSULES) PATIENTS WILL BE REASSESSED, AND THEN TREATED WITH ORAL CHOLESTYRAMINE 6 G/DAY (500 MG CAPSULES -> 4 CAPSULES PER EACH MEAL/DAY) DURING 12 WEEKS AND E SAME INITIAL EVALUATION WILL BE REPEATED
Drug: CHOLESTYRAMINE
CHOLESTYRAMINE CAPSULES, 6 G/DAY P.O. DURING 12 WEEKS
Other Name: QUESTRAN




Primary Outcome Measures :
  1. CML SERUM LEVELS [ Time Frame: 12 WEEKS ]
    REDUCTION OF CARBOXYMETHYL (CML) SERUM LEVELS


Secondary Outcome Measures :
  1. OPTICAL NERVE CONDUCTION [ Time Frame: 12 WEEKS ]
    CHANGE IN OPTICAL NERVE CONDUCTION AFTER VISUAL STIMULUS RESPECT PLACEBO

  2. MULTIFOCAL ELECTRORETINOGRAPHY [ Time Frame: 12 WEEKS ]
    SIGNIFICANT CHANGE RESPECT PLACEBO



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Ages Eligible for Study:   25 Years to 50 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • TYPE 2 DIABETES
  • More than 5 and less than 10 years of disease
  • Adherent to treatment with oral hypoglycemic agents or insulin
  • Agree to participate in the study through a written informed consent.
  • High habitual intake of AGEs according the food recall .

Exclusion Criteria:

  • Severe Obesity (BMI> 35 kg / m2)
  • Glycosylated hemoglobin> 9%, anemia, renal failure (creatinine> 1.5 mg / dL or calculated creatinine clearance <60 ml / min), fasting plasma glucose> 250 mg / dL
  • History of acute hyperglycemic complications requiring hospitalization in the past 2 years
  • Severe diabetic dyslipidemia (LDL> 130, TG> 350 mg / dL)
  • Vitamin B12 deficiency
  • History of heart, liver, lung cancer or chronic diseases
  • Clinical diagnosis of diabetic neiropathy and eye conditions that could hinder electroretinogram, such as uncorrected refractive defects, cataracts and severe diabetic retinopathy or macular edema.
  • Poorly controlled hypertension or acute vascular event in the past 2 years
  • Pregnancy.

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02249897


Locations
Chile
Institute of Nutrition & Food Technology (INTA)
Santiago, Metropolitan Region, Chile, 7830490
Clinica Alemana de Santiago
Santiago, Region Metropolitana, Chile
Sponsors and Collaborators
University of Chile
Clinica Alemana de Santiago
Investigators
Principal Investigator: MARIA PIA DE LA MAZA, PROFESSOR INSTITUTE OF NUTRITION & FOOD TECHNOLOGY, UNIVERSITY OF CHILE

Responsible Party: MARIA PIA DE LA MAZA, Professor, University of Chile
ClinicalTrials.gov Identifier: NCT02249897     History of Changes
Other Study ID Numbers: AGE-1
First Posted: September 26, 2014    Key Record Dates
Last Update Posted: February 14, 2018
Last Verified: February 2018

Additional relevant MeSH terms:
Diabetic Retinopathy
Diabetic Neuropathies
Retinal Diseases
Eye Diseases
Diabetic Angiopathies
Vascular Diseases
Cardiovascular Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Cholestyramine Resin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents