<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02249897</url>
  </required_header>
  <id_info>
    <org_study_id>AGE-1</org_study_id>
    <nct_id>NCT02249897</nct_id>
  </id_info>
  <brief_title>PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs</brief_title>
  <acronym>PREL-AGES</acronym>
  <official_title>PRELIMINARY EVALUATION OF RETINAL EFFECTS OF PHARMACOLOLOGICAL LOWERING OF SERUM LEVES OF ADVANCED GLYCATION END-PRODUCTS (AGEs) IN TYPE 2 DIABETIC PATIENTS</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Chile</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Clinica Alemana de Santiago</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Chile</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is evidence of the association between diabetic microangiopathy and elevated serum&#xD;
      concentrations of advanced glycation end-products (AGEs). AGEs levels are associated with&#xD;
      ingestion of specific foods (baked meats and milk powder); reducing their dietary intake&#xD;
      lowers AGEs concentrations, with beneficial metabolic effects; however threre is still no&#xD;
      evidence of whether this has an impact on microvascular complications of DM. We recently&#xD;
      applied for funding to compare in a RCT the effects of Cholestyramine versus placebo, on&#xD;
      visual electrophysiology. This drug is similar to Sevelamer in structure, both act as&#xD;
      chelators of bile salts, and reduce absorption of dietary AGE, lowering serum levels. However&#xD;
      it is essential to carry out preliminary tests to assess aspects that may imply adjustments&#xD;
      to the proposed protocol, such as: 1) tolerance to the drug 2) short term effect of the drug&#xD;
      versus placebo on serum levels of AGEs 3) effects of the drug versus placebo in levels of fat&#xD;
      soluble vitamins (D and K specifically) 4) intra and interindividual variability of&#xD;
      electrophysiological measurements of vision (ERGMF and optic nerve conduction velocity) 5)&#xD;
      drug versus placebo in electrophysiological measurements of vision (neuroconduction ERGMF and&#xD;
      optic nerve). Objective: The present project is planned as a pilot study, which will clarify&#xD;
      points 1 to 5. Methodology: patients (6 DM2, 25 -50 y) will be assessed through&#xD;
      anthropometry, clinical laboratory tests (creatinine, chemistry profile, lipid profile,&#xD;
      microalbuminuria glycosylated hemoglobin, vitamin B12, 25OH vitamin D and prothrombin),&#xD;
      dietary recalls specifically designed to analyze the regular consumption of AGEs, serum CML&#xD;
      and neuro-ophthalmological study (fundus, ERGMF and optic nerve conduction). Subsequently&#xD;
      each patient will be assigned to treatment with placebo for 3 months and then Cholestyramine&#xD;
      6 g / day for 12 weeks and at the end of each period will be reassessed using the same&#xD;
      methodology. If patients cannot tolerate the drug, they will be assigned to a reduced AGE&#xD;
      diet.&#xD;
&#xD;
      Expected results: Cholestyramine will have side effect similar to placebo (mainly digestive).&#xD;
      The active drug and not placebo will reduce serum levels of AGEs and electrophysiological&#xD;
      parameters of vision at 12 weeks. It is expected that a low AGEs diet in patients who do not&#xD;
      tolerate the drug will also reduce serum CML although to a lesser degree and will also induce&#xD;
      electrophysiologic changes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients: 6 adults with type 2diabetes will be selected, ages between 25 and 50 years, with&#xD;
      more than 5 and less than 10 years of disease, adherent to treatment with oral hypoglycemic&#xD;
      agents or insulin, who agree to participate in the study through a written informed consent.&#xD;
      Only those with a high habitual intake of AGEs according the food recall will be included.&#xD;
      Patients with the following characteristics will be excluded: -Severe Obesity (BMI&gt; 35 kg /&#xD;
      m2), glycosylated hemoglobin&gt; 9%, anemia, renal failure (creatinine&gt; 1.5 mg / dL or&#xD;
      calculated creatinine clearance &lt;60 ml / min), fasting plasma glucose&gt; 250 mg / dL or a&#xD;
      history of acute hyperglycemic complications requiring hospitalization in the past 2 years,&#xD;
      severe diabetic dyslipidemia (LDL&gt; 130, TG&gt; 350 mg / dL) or vitamin B12 deficiency, a history&#xD;
      of heart, liver, lung cancer or chronic diseases, clinical diagnosis of diabetic neuropathy&#xD;
      and eye conditions that could hinder electroretinogram, such as uncorrected refractive&#xD;
      defects, cataracts and severe diabetic retinopathy or macular edema. Other exclusion criteria&#xD;
      will be poorly controlled hypertension or acute vascular event in the past 2 years and&#xD;
      pregnancy.&#xD;
&#xD;
      After signing an informed consent, patients will undergo the following assessments: 1)&#xD;
      History and drug registration. 2) dietary survey including methods of food preparation,&#xD;
      consumption of dietary products containing fructose or corn starches and specific foods rich&#xD;
      in AGEs according to measurements made in Chilean foods (milk and concentrated powder,&#xD;
      biscuits, cheeses was also specifically recorded, roasted meats and grilled sausages etc.).&#xD;
      3) anthropometry (weight, height, waist circumference) 4) fasting basic laboratory tests&#xD;
      fasting (hemoglobin, TSH, glucose, glycosylated hemoglobin, creatinine, prothrombin, lipid&#xD;
      profile and serum levels of vitamin B12 and vitamin D), using automated clinical laboratory&#xD;
      techniques. 5) morning urine for determination of microalbuminuria (MAU / creatinine) 6)&#xD;
      Inflammatory markers (ultrasensitive PCR) using a commercial ELISA kit. 7) Concentration of&#xD;
      serum AGEs (CML through Abcam ELISA Antibody) 8) Visual evoked potentials as indicator of&#xD;
      electrophysiological conduction after visual stimulation through the optic nerve (ON)&#xD;
      exploring the visual pathway (myelin) to the occipital cortex. 9) ophtalmologic examination&#xD;
      with biomicroscopy for evaluation of refractive defects and fundus (to diagnose the presence&#xD;
      or absence of retinopathy) and evoked potentials by multifocal electroretinography.&#xD;
&#xD;
      This series of evaluations will be repeated after each each treatment period of 12 weeks&#xD;
      each, ie on 3 occasions. Indications and reinforcement of traditional dietary measures to&#xD;
      improve glycemic control (restriction of caloric intake according to body composition,&#xD;
      decrease of intake of simple carbohydrates and increase of soluble and insoluble fiber to&#xD;
      reduce glycemic load), according to the standards for diabetes management from the Ministry&#xD;
      of Health. Also if necessary the hypoglycemic or insulin therapy will be adjusted in order to&#xD;
      achieve adequate metabolic control (HbA1c &lt;7%).&#xD;
&#xD;
      For the specific drug treatment, initially inert placebo (talc) capsuleswill be prescribed&#xD;
      during 12 weeks then switching to Cholestyramine during 12 weeks, with equal physical&#xD;
      characteristics of capsules, after which all initial evaluations be repeated. Cholestyramine&#xD;
      treatment will be prescribed using a 6 g daily dose (4 tablets daily of 500 mg each of&#xD;
      cholestyramine with each main meal). Patients that manifest adverse effects with the use of&#xD;
      the active drug and cannot maintain the treatment, will be assigned to a dietary treatment&#xD;
      with a reduced AGE diet according to the recommendations of Uribarri et. al. (32) for 12&#xD;
      weeks, at the end of which the initial evaluation will be repeated. In both periods&#xD;
      supplementation with vitamin D in doses adjusted to pre-intervention, vitamin A and E in&#xD;
      adequate doses to meet the DRI level and vitamin K if needed will be prescribed. Patients&#xD;
      will be monitored monthly by their treating diabetologist, verifying compliance, registering&#xD;
      adverse events, anthropometric measurements and fasting blood glucose. If elevated blood&#xD;
      glucose levels are detected infectious causes or failure to adhere dietary indications will&#xD;
      be discarded and corrective measures will be initiated. In patients who do not meet the&#xD;
      inclusion criteria due to vitamin B12 deficiency, intramuscular supplementation will be&#xD;
      indicated and will be referred to their respective centers. If vitamin D deficiency is&#xD;
      detected, proper supplementation before entering the study will be indicated. At the end of&#xD;
      the control period (placebo for 12 weeks), the same initial assessments will be repeated and&#xD;
      then a second treatment (cholestyramine 6 g / day) will be assigned, repeating the same&#xD;
      assessments at the end of these 3 months.&#xD;
&#xD;
      Blood samples for determination of CML and ultrasensitive PCR will remain frozen at -70&#xD;
      degrees to be processed all at the end of the study, avoiding to make any technical changes&#xD;
      on 2 times. Instead determinations to be made in clinical laboratory (TSH, prothrombin,&#xD;
      glycemia, lipid profile, creatinine, glycated hemoglobin, microalbuminuria and levels of&#xD;
      vitamins B12 and D), will be processed immediately, delivering a copy of the results to each&#xD;
      patient to facilitate corrective measures necessary.&#xD;
&#xD;
      Primary endpoint and sample size: For this pilot study sample size was not estimated because&#xD;
      one of the objectives is to assess variability and detect whether the short period of&#xD;
      treatment does induce changes in electrophysiological variables that are clearly detectable,&#xD;
      in addition to assessing drug tolerance. With this information you can better estimate the&#xD;
      sample size for a randomized controlled larger. In addition it was felt necessary to begin&#xD;
      the study using the placebo and no treatment assigned randomly because washout period would&#xD;
      be necessary for a randomized crossover study of random type is unknown. The proposed (6&#xD;
      patients) sample size was calculated based on the available budget. It is important to note&#xD;
      that analysis of evoked potentials and electroretinography considers each eye separately, so&#xD;
      that there will be 12 eyes in 6 patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2015</start_date>
  <completion_date type="Actual">December 2017</completion_date>
  <primary_completion_date type="Actual">December 2017</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <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)</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>CML SERUM LEVELS</measure>
    <time_frame>12 WEEKS</time_frame>
    <description>REDUCTION OF CARBOXYMETHYL (CML) SERUM LEVELS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>OPTICAL NERVE CONDUCTION</measure>
    <time_frame>12 WEEKS</time_frame>
    <description>CHANGE IN OPTICAL NERVE CONDUCTION AFTER VISUAL STIMULUS RESPECT PLACEBO</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>MULTIFOCAL ELECTRORETINOGRAPHY</measure>
    <time_frame>12 WEEKS</time_frame>
    <description>SIGNIFICANT CHANGE RESPECT PLACEBO</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>DIABETES</condition>
  <condition>DIABETIC RETINOPATHY</condition>
  <condition>DIABETIC NEUROPATHY</condition>
  <arm_group>
    <arm_group_label>PLACEBO</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>CHOLESTIRAMINE</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>AFTER COMPLETING THE CONTROL PERIOD (PLACEBO CAPSULES) PATIENTS WILL BE REASSESSED, AND THEN TREATED WITH ORAL CHOLESTYRAMINE 6 G/DAY (500 MG CAPSULES -&gt; 4 CAPSULES PER EACH MEAL/DAY) DURING 12 WEEKS AND E SAME INITIAL EVALUATION WILL BE REPEATED</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CHOLESTYRAMINE</intervention_name>
    <description>CHOLESTYRAMINE CAPSULES, 6 G/DAY P.O. DURING 12 WEEKS</description>
    <arm_group_label>CHOLESTIRAMINE</arm_group_label>
    <arm_group_label>PLACEBO</arm_group_label>
    <other_name>QUESTRAN</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  TYPE 2 DIABETES&#xD;
&#xD;
          -  More than 5 and less than 10 years of disease&#xD;
&#xD;
          -  Adherent to treatment with oral hypoglycemic agents or insulin&#xD;
&#xD;
          -  Agree to participate in the study through a written informed consent.&#xD;
&#xD;
          -  High habitual intake of AGEs according the food recall .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Severe Obesity (BMI&gt; 35 kg / m2)&#xD;
&#xD;
          -  Glycosylated hemoglobin&gt; 9%, anemia, renal failure (creatinine&gt; 1.5 mg / dL or&#xD;
             calculated creatinine clearance &lt;60 ml / min), fasting plasma glucose&gt; 250 mg / dL&#xD;
&#xD;
          -  History of acute hyperglycemic complications requiring hospitalization in the past 2&#xD;
             years&#xD;
&#xD;
          -  Severe diabetic dyslipidemia (LDL&gt; 130, TG&gt; 350 mg / dL)&#xD;
&#xD;
          -  Vitamin B12 deficiency&#xD;
&#xD;
          -  History of heart, liver, lung cancer or chronic diseases&#xD;
&#xD;
          -  Clinical diagnosis of diabetic neiropathy and eye conditions that could hinder&#xD;
             electroretinogram, such as uncorrected refractive defects, cataracts and severe&#xD;
             diabetic retinopathy or macular edema.&#xD;
&#xD;
          -  Poorly controlled hypertension or acute vascular event in the past 2 years&#xD;
&#xD;
          -  Pregnancy.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>25 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>MARIA PIA DE LA MAZA, PROFESSOR</last_name>
    <role>Principal Investigator</role>
    <affiliation>INSTITUTE OF NUTRITION &amp; FOOD TECHNOLOGY, UNIVERSITY OF CHILE</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Institute of Nutrition &amp; Food Technology (INTA)</name>
      <address>
        <city>Santiago</city>
        <state>Metropolitan Region</state>
        <zip>7830490</zip>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clinica Alemana de Santiago</name>
      <address>
        <city>Santiago</city>
        <state>Region Metropolitana</state>
        <country>Chile</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Chile</country>
  </location_countries>
  <verification_date>February 2018</verification_date>
  <study_first_submitted>September 17, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>February 12, 2018</last_update_submitted>
  <last_update_submitted_qc>February 12, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">February 14, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Chile</investigator_affiliation>
    <investigator_full_name>MARIA PIA DE LA MAZA</investigator_full_name>
    <investigator_title>Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetic Neuropathies</mesh_term>
    <mesh_term>Diabetic Retinopathy</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cholestyramine Resin</mesh_term>
  </intervention_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02249897
org study id: AGE-1
nct id: NCT02249897
lead sponsor: 
collaborator: 
has dmc: Yes
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.
Patients: 6 adults with type 2diabetes will be selected, ages between 25 and 50 years, with
      more than 5 and less than 10 years of disease, adherent to treatment with oral hypoglycemic
      agents or insulin, who agree to participate in the study through a written informed consent.
      Only those with a high habitual intake of AGEs according the food recall will be included.
      Patients with the following characteristics will be excluded: -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 or a
      history of acute hyperglycemic complications requiring hospitalization in the past 2 years,
      severe diabetic dyslipidemia (LDL> 130, TG> 350 mg / dL) or vitamin B12 deficiency, a history
      of heart, liver, lung cancer or chronic diseases, clinical diagnosis of diabetic neuropathy
      and eye conditions that could hinder electroretinogram, such as uncorrected refractive
      defects, cataracts and severe diabetic retinopathy or macular edema. Other exclusion criteria
      will be poorly controlled hypertension or acute vascular event in the past 2 years and
      pregnancy.

      After signing an informed consent, patients will undergo the following assessments: 1)
      History and drug registration. 2) dietary survey including methods of food preparation,
      consumption of dietary products containing fructose or corn starches and specific foods rich
      in AGEs according to measurements made in Chilean foods (milk and concentrated powder,
      biscuits, cheeses was also specifically recorded, roasted meats and grilled sausages etc.).
      3) anthropometry (weight, height, waist circumference) 4) fasting basic laboratory tests
      fasting (hemoglobin, TSH, glucose, glycosylated hemoglobin, creatinine, prothrombin, lipid
      profile and serum levels of vitamin B12 and vitamin D), using automated clinical laboratory
      techniques. 5) morning urine for determination of microalbuminuria (MAU / creatinine) 6)
      Inflammatory markers (ultrasensitive PCR) using a commercial ELISA kit. 7) Concentration of
      serum AGEs (CML through Abcam ELISA Antibody) 8) Visual evoked potentials as indicator of
      electrophysiological conduction after visual stimulation through the optic nerve (ON)
      exploring the visual pathway (myelin) to the occipital cortex. 9) ophtalmologic examination
      with biomicroscopy for evaluation of refractive defects and fundus (to diagnose the presence
      or absence of retinopathy) and evoked potentials by multifocal electroretinography.

      This series of evaluations will be repeated after each each treatment period of 12 weeks
      each, ie on 3 occasions. Indications and reinforcement of traditional dietary measures to
      improve glycemic control (restriction of caloric intake according to body composition,
      decrease of intake of simple carbohydrates and increase of soluble and insoluble fiber to
      reduce glycemic load), according to the standards for diabetes management from the Ministry
      of Health. Also if necessary the hypoglycemic or insulin therapy will be adjusted in order to
      achieve adequate metabolic control (HbA1c <7%).

      For the specific drug treatment, initially inert placebo (talc) capsuleswill be prescribed
      during 12 weeks then switching to Cholestyramine during 12 weeks, with equal physical
      characteristics of capsules, after which all initial evaluations be repeated. Cholestyramine
      treatment will be prescribed using a 6 g daily dose (4 tablets daily of 500 mg each of
      cholestyramine with each main meal). Patients that manifest adverse effects with the use of
      the active drug and cannot maintain the treatment, will be assigned to a dietary treatment
      with a reduced AGE diet according to the recommendations of Uribarri et. al. (32) for 12
      weeks, at the end of which the initial evaluation will be repeated. In both periods
      supplementation with vitamin D in doses adjusted to pre-intervention, vitamin A and E in
      adequate doses to meet the DRI level and vitamin K if needed will be prescribed. Patients
      will be monitored monthly by their treating diabetologist, verifying compliance, registering
      adverse events, anthropometric measurements and fasting blood glucose. If elevated blood
      glucose levels are detected infectious causes or failure to adhere dietary indications will
      be discarded and corrective measures will be initiated. In patients who do not meet the
      inclusion criteria due to vitamin B12 deficiency, intramuscular supplementation will be
      indicated and will be referred to their respective centers. If vitamin D deficiency is
      detected, proper supplementation before entering the study will be indicated. At the end of
      the control period (placebo for 12 weeks), the same initial assessments will be repeated and
      then a second treatment (cholestyramine 6 g / day) will be assigned, repeating the same
      assessments at the end of these 3 months.

      Blood samples for determination of CML and ultrasensitive PCR will remain frozen at -70
      degrees to be processed all at the end of the study, avoiding to make any technical changes
      on 2 times. Instead determinations to be made in clinical laboratory (TSH, prothrombin,
      glycemia, lipid profile, creatinine, glycated hemoglobin, microalbuminuria and levels of
      vitamins B12 and D), will be processed immediately, delivering a copy of the results to each
      patient to facilitate corrective measures necessary.

      Primary endpoint and sample size: For this pilot study sample size was not estimated because
      one of the objectives is to assess variability and detect whether the short period of
      treatment does induce changes in electrophysiological variables that are clearly detectable,
      in addition to assessing drug tolerance. With this information you can better estimate the
      sample size for a randomized controlled larger. In addition it was felt necessary to begin
      the study using the placebo and no treatment assigned randomly because washout period would
      be necessary for a randomized crossover study of random type is unknown. The proposed (6
      patients) sample size was calculated based on the available budget. It is important to note
      that analysis of evoked potentials and electroretinography considers each eye separately, so
      that there will be 12 eyes in 6 patients.
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)
primary purpose: Prevention
masking: None (Open Label)
measure: CML SERUM LEVELS
time frame: 12 WEEKS
description: REDUCTION OF CARBOXYMETHYL (CML) SERUM LEVELS
measure: OPTICAL NERVE CONDUCTION
time frame: 12 WEEKS
description: CHANGE IN OPTICAL NERVE CONDUCTION AFTER VISUAL STIMULUS RESPECT PLACEBO
measure: MULTIFOCAL ELECTRORETINOGRAPHY
time frame: 12 WEEKS
description: SIGNIFICANT CHANGE RESPECT PLACEBO
arm group label: PLACEBO
arm group type: Placebo Comparator
description: 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
arm group label: CHOLESTIRAMINE
arm group type: Active Comparator
description: 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
intervention type: Drug
intervention name: CHOLESTYRAMINE
description: CHOLESTYRAMINE CAPSULES, 6 G/DAY P.O. DURING 12 WEEKS
arm group label: CHOLESTIRAMINE
arm group label: PLACEBO
other name: QUESTRAN
criteria: 
gender: All
minimum age: 25 Years
maximum age: 50 Years
healthy volunteers: No
last name: MARIA PIA DE LA MAZA, PROFESSOR
role: Principal Investigator
affiliation: INSTITUTE OF NUTRITION & FOOD TECHNOLOGY, UNIVERSITY OF CHILE
facility: 
facility: 
country: Chile
responsible party type: Principal Investigator
investigator affiliation: University of Chile
investigator full name: MARIA PIA DE LA MAZA
investigator title: Professor
mesh term: Diabetic Neuropathies
mesh term: Diabetic Retinopathy
mesh term: Cholestyramine Resin