SIMOX - Induction of Oxidative Stress (SIMOX)

SIMOX - A Randomized, Double-blinded, Placebo Controlled Study of Simvastatins Possible Effect on Oxidative Stress on Healthy Volunteers

The purpose of the study is to investigate if use of simvastatin is associated with the level of oxidative stress in humans. The association is examined by comparing changes in oxidative stress in a group treated with simvastatin with the change in a placebo group. The study is a randomized-based, double-blinded placebo-controlled study. Each treatment group consists of 20 healthy male volunteers who consume simvastatin or placebo over 14 days. The induction of oxidative stress is measured by 8-oxoguanosine and 8- oxodeoxyguanosine, isolated from urine. A t-test will be performed to compare drug treatment with placebo. The results will be published.

Study Overview

• Status: Completed
• Conditions: Oxidative Stress
• Intervention / Treatment: Drug: Simvastatin; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2100
    • Department of Clinical Pharmacology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Caucasian
• healthy men
• 18-50 years
• BMI: 18-30

Exclusion Criteria:

• Total cholesterol less than 3 mmol/L
• Use of natural and herbal medicines that is affected/affects simvastatin:

anion exchangers, amiodarone, amlodipine, ciclosporin, clarithromycin, colchicine, danazol, diltiazem, erythromycin, fibrates, fluconazole, fusidin acid, grape fruit juice, HIV protease inhibitors, itraconazole, ketoconazole, nefazodone, niacin, posaconazole, rifampicin, telithromycin, verapamil, vitamin K-antagonists, voriconazole

• following diseases: a Coronary vascular disease b Renal insufficiency c Hepatic insufficiency d heart failure e Previous heart arrythmia f Hypokalaemia g Low blood pressure h hyperthyroidism i muscular toxicity j galactose intolerants k Lapp Lactase deficiency l Glucose/galactose-malabsorption m Psychiatric disorder
• allergies towards any of the tested medicine
• intake of narcotics within 2 months prior to trial
• intake of supplements within 2 months prior to trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Simvastatin; 2 Simvastatin capsules of 20 mg every evening for 14 days	Drug: Simvastatin; 2 Simvastatin capsules of 20 mg every evening for 14 days
Placebo Comparator: Placebo; 2 placebo capsules every evening for 14 days	Drug: Placebo; 2 placebo capsules every evening for 14 days

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Urinary excretion of 8-oxoguanosine (nmol/24h)	Change from Baseline after fourteen days of treatment
Urinary excretion of 8-oxodeoxyguanosine (nmol/24h)	Change from Baseline after fourteen days of treatment

Secondary Outcome Measures

Outcome Measure	Time Frame
Malondialdehyde	Change from Baseline after fourteen days of treatment
Vitamin C	Change from Baseline after fourteen days of treatment
Vitamin E	Change from Baseline after fourteen days of treatment
Biopterin	Change from Baseline after fourteen days of treatment

Collaborators and Investigators

• Sponsor: Rigshospitalet, Denmark
• Collaborators: Klinisk Biokemisk Afdeling; Klinisk farmakologisk Afdeling; Sektion for Biomedicin Institut for Veterinær Patobiologi
• Investigators: Principal Investigator: Henrik Enghusen Poulsen, Professor MD, Department Head

Study record dates

Study Major Dates

• Study Start: September 1, 2014
• Primary Completion (Actual): February 1, 2015
• Study Completion (Actual): February 1, 2015

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 30, 2014
• First Posted (Estimate): October 3, 2014

Study Record Updates

• Last Update Posted (Estimate): March 10, 2015
• Last Update Submitted That Met QC Criteria: March 9, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Oxidative stress; Simvastatin
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Simvastatin
• Other Study ID Numbers: 2014-647