Statins for Oxidative Stress and Mitochondrial Function in Diabetic Polyneuropathy
Ezetimibe/Simvastatin and Rosuvastatin for Oxidative Stress and Mitochondrial Function in Diabetic Polyneuropathy: a Randomized, Double Blinded, Placebo Controlled Clinical Trial
1 other identifier
interventional
74
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_2
Started Feb 2012
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
February 1, 2012
CompletedPrimary Completion
Last participant's last visit for primary outcome
January 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2014
CompletedFirst Submitted
Initial submission to the registry
April 30, 2014
CompletedFirst Posted
Study publicly available on registry
May 2, 2014
CompletedMay 6, 2014
May 1, 2014
1.9 years
April 30, 2014
May 5, 2014
Conditions
Keywords
Outcome Measures
Primary Outcomes (3)
lipid peroxidation
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.
16 weeks
Nitric oxide
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.
16 weeks
Total antioxidant capacity
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®).
16 weeks
Secondary Outcomes (3)
neuropathic symptoms score
16 weeks
neuropathic impairment score
16 weeks
nerve conduction studies
16 weeks
Other Outcomes (3)
Creatinin
16 weeks
aspartate aminotransferase
16 weeks
alanine aminotransferase
16 weeks
Study Arms (3)
placebo
PLACEBO COMPARATORcalcined magnesia 100 mg tablets once a day for 16 weeks
ezetimibe/simvastatin
ACTIVE COMPARATORezetimibe/simvastatin 10/20 mg tablets once a day for 16 weeks
rosuvastatin
ACTIVE COMPARATORrosuvastatin 20 mg tablets once a day for 16 weeks
Interventions
We ensured the patient took the drug at night before meals
We ensured the patient took the drug at night before meals
We ensured the patient took the drug at night before meals
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- Renal or hepatic failure
- Pregnant or breastfeeding
- Other neuropathies (alcohol-induced, radiculopathy, autoimmune, cancer-related)
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Cardiovascular Research Unit
Guadalajara, Jalisco, 44340, Mexico
Related Publications (2)
Hernandez-Ojeda J, Cardona-Munoz EG, Roman-Pintos LM, Troyo-Sanroman R, Ortiz-Lazareno PC, Cardenas-Meza MA, Pascoe-Gonzalez S, Miranda-Diaz AG. The effect of ubiquinone in diabetic polyneuropathy: a randomized double-blind placebo-controlled study. J Diabetes Complications. 2012 Jul-Aug;26(4):352-8. doi: 10.1016/j.jdiacomp.2012.04.004. Epub 2012 May 16.
PMID: 22595020BACKGROUNDVillegas-Rivera G, Roman-Pintos LM, Cardona-Munoz EG, Arias-Carvajal O, Rodriguez-Carrizalez AD, Troyo-Sanroman R, Pacheco-Moises FP, Moreno-Ulloa A, Miranda-Diaz AG. Effects of Ezetimibe/Simvastatin and Rosuvastatin on Oxidative Stress in Diabetic Neuropathy: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Oxid Med Cell Longev. 2015;2015:756294. doi: 10.1155/2015/756294. Epub 2015 Jul 28.
PMID: 26290682DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- 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
Study Design
- Study Type
- interventional
- Phase
- phase 2
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- PhD, MD, FACS
Study Record Dates
First Submitted
April 30, 2014
First Posted
May 2, 2014
Study Start
February 1, 2012
Primary Completion
January 1, 2014
Study Completion
April 1, 2014
Last Updated
May 6, 2014
Record last verified: 2014-05