PRELIMINARY EVALUATION OF PHARMACOLOGICAL LOWERING OF AGEs

NCT02249897 | Completed Phase 4 DMC

• 1 other identifier: AGE-1
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 2

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.

Conditions

DIABETES; DIABETIC RETINOPATHY; DIABETIC NEUROPATHY

Outcome Measures

Primary Outcomes (1)

• CML SERUM LEVELS

  REDUCTION OF CARBOXYMETHYL (CML) SERUM LEVELS

  12 WEEKS

Secondary Outcomes (2)

• OPTICAL NERVE CONDUCTION

  12 WEEKS

• MULTIFOCAL ELECTRORETINOGRAPHY

  12 WEEKS

Study Arms (2)

PLACEBO

PLACEBO COMPARATOR

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

CHOLESTIRAMINE

ACTIVE COMPARATOR

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

Interventions

CHOLESTYRAMINE DRUG

CHOLESTYRAMINE CAPSULES, 6 G/DAY P.O. DURING 12 WEEKS

Also known as: QUESTRAN

CHOLESTIRAMINE; PLACEBO

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 .

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Chile: lead
• Clinica Alemana de Santiago: collaborator

Study Sites (2)

Institute of Nutrition & Food Technology (INTA)

Santiago, Metropolitan Region, 7830490, Chile

Location

Clinica Alemana de Santiago

Santiago, Santiago Metropolitan, Chile

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetic Retinopathy; Diabetic Neuropathies

Interventions

Cholestyramine Resin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Retinal Diseases; Eye Diseases; Diabetic Angiopathies; Vascular Diseases; Cardiovascular Diseases; Diabetes Complications; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Polystyrenes; Plastics; Polymers; Macromolecular Substances; Biomedical and Dental Materials; Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• MARIA PIA DE LA MAZA, PROFESSOR

  INSTITUTE OF NUTRITION & FOOD TECHNOLOGY, UNIVERSITY OF CHILE

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Prescription of 6 g oral cholestiramine in 7 patients with type 2 DM, to study changes in neuroophtalmologic variables (electroretinogram and optic nerve conduction)

Study Record Dates

• First Submitted: September 17, 2014
• First Posted: September 26, 2014
• Study Start: January 1, 2015
• Primary Completion: December 1, 2017
• Study Completion: December 1, 2017
• Last Updated: February 14, 2018

Record last verified: 2018-02

Locations

CL (2)