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Statins for Oxidative Stress and Mitochondrial Function in Diabetic Polyneuropathy

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ClinicalTrials.gov Identifier: NCT02129231
Recruitment Status : Completed
First Posted : May 2, 2014
Last Update Posted : May 6, 2014
Sponsor:
Information provided by (Responsible Party):
Alejandra Guillermina Miranda Diaz, University of Guadalajara

Brief Summary:

Aims: To evaluate the effect of ezetimibe/simvastatin and rosuvastatin on oxidative stress and mitochondrial function in patients with DPN.

Methods: We performed a randomized, double-blinded, placebo-controlled phase II clinical trial in adult patients with type 2 Diabetes Mellitus (T2DM) who had Diabetic Polyneuropathy (DPN) evaluated by composite scores and nerve conduction studies (NCS), HBA1C <12% (108 mmol/mol), previous exclusion of other neuropathies. Ninety-eight persons with T2DM were allocated 1:1:1 to either placebo, ezetimibe/simvastatin 10/20 mg or rosuvastatin 20 mg for 16 weeks, and healthy controls (not randomized) were included for comparisons. Primary outcomes were lipid peroxidation (LPO), nitric oxide (NO), and total antioxidant capacity (TAC); secondary were clinical, NCS and metabolic parameters. Results were expressed as mean ± standard deviation (SD) or standard error of the mean (SEM), frequencies and percentages. Non-parametric analysis was used.


Condition or disease Intervention/treatment Phase
Oxidative Stress Diabetic Polyneuropathy Drug: calcined magnesia Drug: Ezetimibe/simvastatin Drug: Rosuvastatin Phase 2

  Show Detailed Description

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Official Title: Ezetimibe/Simvastatin and Rosuvastatin for Oxidative Stress and Mitochondrial Function in Diabetic Polyneuropathy: a Randomized, Double Blinded, Placebo Controlled Clinical Trial
Study Start Date : February 2012
Actual Primary Completion Date : January 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: placebo
calcined magnesia 100 mg tablets once a day for 16 weeks
Drug: calcined magnesia
We ensured the patient took the drug at night before meals
Other Name: placebo

Active Comparator: ezetimibe/simvastatin
ezetimibe/simvastatin 10/20 mg tablets once a day for 16 weeks
Drug: Ezetimibe/simvastatin
We ensured the patient took the drug at night before meals
Other Names:
  • Zintrepid
  • Vytorin

Active Comparator: rosuvastatin
rosuvastatin 20 mg tablets once a day for 16 weeks
Drug: Rosuvastatin
We ensured the patient took the drug at night before meals
Other Name: Crestor




Primary Outcome Measures :
  1. lipid peroxidation [ Time Frame: 16 weeks ]
    LPO was measured according to kit specifications (Oxford Biomedical Research Inc., FR12), 200 μL of serum where processed with a chromogen substance that reacts with malondialdehyde (MDA) and 4-hydroxy-alkenals (HNA), the absorbance measured at 586 nm, and results expressed in nmol/mL.

  2. Nitric oxide [ Time Frame: 16 weeks ]
    Previous deproteinization of the samples, we performed a colorimetric for determining the concentration of NO with 85 µL of serum (Nitric Oxide Assay Kit, User protocol 482650), with results expressed as pmol/mL.

  3. Total antioxidant capacity [ Time Frame: 16 weeks ]
    Total antioxidant capacity (TAC) was realized with 200 µL of serum, to obtain values of mM equivalent of uric acid (Total Antioxidant Power Kit, No. 02090130, Oxford Biomedical Research®).


Secondary Outcome Measures :
  1. neuropathic symptoms score [ Time Frame: 16 weeks ]
    Symptoms referred by the patient as pain and discomfort

  2. neuropathic impairment score [ Time Frame: 16 weeks ]
    Neuropathic signs assessed by the physician through neurological techniques previously published by Dyck et. al.

  3. nerve conduction studies [ Time Frame: 16 weeks ]
    Latency, duration, amplitude and motor nerve conduction velocity from fibula, tibial, median and ulnae nerves, and sensitivity parameters from sural, median and ulnae nerves, as required by the American Association of Electrodiagnostic Medicine.


Other Outcome Measures:
  1. Creatinin [ Time Frame: 16 weeks ]
    We measured creatinin to evaluate renal function.

  2. aspartate aminotransferase [ Time Frame: 16 weeks ]
    We measured aspartate aminotransferase regarding hepatic function.

  3. alanine aminotransferase [ Time Frame: 16 weeks ]
    We measured alanine aminotransferase regarding hepatic function.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • 18 years old and older
  • Type 2 Diabetes Mellitus according to American Diabetes Association
  • Diabetic Polyneuropathy by Dyck et. al. criteria
  • HbA1c <12%
  • Informed consent signed

Exclusion Criteria:

  • Renal or hepatic failure
  • Pregnant or breastfeeding
  • Other neuropathies (alcohol-induced, radiculopathy, autoimmune, cancer-related)

Information from the National Library of Medicine

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): NCT02129231


Locations
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Mexico
Cardiovascular Research Unit
Guadalajara, Jalisco, Mexico, 44340
Sponsors and Collaborators
University of Guadalajara
Investigators
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Study Chair: Luis M Roman-Pintos, PhD, MD University of Guadalajara
Study Director: Alejandra G Miranda-Diaz, PhD,MD,FACS University of Guadalajara
Study Chair: Adolfo D Rodriguez-Carrizalez, PhD, MD University of Guadalajara
Study Chair: Geannyne Villegas-Rivera, PhD, MD University of Guadalajara

Publications:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Alejandra Guillermina Miranda Diaz, PhD, MD, FACS, University of Guadalajara
ClinicalTrials.gov Identifier: NCT02129231     History of Changes
Other Study ID Numbers: STAT/DPN_2014
First Posted: May 2, 2014    Key Record Dates
Last Update Posted: May 6, 2014
Last Verified: May 2014

Keywords provided by Alejandra Guillermina Miranda Diaz, University of Guadalajara:
ezetimibe/simvastatin
rosuvastatin
diabetic polyneuropathy
oxidative stress
mitochondrial dysfunction

Additional relevant MeSH terms:
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Polyneuropathies
Diabetic Neuropathies
Peripheral Nervous System Diseases
Neuromuscular Diseases
Nervous System Diseases
Diabetes Complications
Diabetes Mellitus
Endocrine System Diseases
Magnesium Oxide
Rosuvastatin Calcium
Simvastatin
Ezetimibe
Ezetimibe, Simvastatin Drug Combination
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors
Antacids
Gastrointestinal Agents