Effect of Simvastatin Withdrawal on Ocular Endothelial Function

NCT ID: NCT02533141

Last Updated: 2020-02-20

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE4
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-10-31
• Study Completion Date: 2020-12-31

Brief Summary

Statins are drugs representing the most commonly prescribed medication for the treatment of hypercholesterolemia. In a recently published study, discontinuation of statin therapy in patients after acute myocardial infarction was associated with a higher all-cause mortality (hazard ratio 3,45) and a higher cardiac mortality (hazard ratio 4,65). Increasing evidence suggests that statins also have vasoactive properties by up-regulating endothelial nitric oxide synthase (eNOS) with positive effects on endothelial function. Experiments with flow-mediated vasodilatation (FMD) showed these positive effects of statin treatment on endothelial function but also revealed that withdrawal of statin treatment transiently worsens endothelial function, independently of serum cholesterol levels.

Consequently, this placebo controlled Phase IV crossover study wants to assess changes of endothelial function in terms of flicker induced vasodilatation before and during statin therapy as well as after statin withdrawal. For this purpose 20 healthy subjects will be treated with 40 mg/day of simvastatin for a period of 4 weeks. Flicker induced vasodilatation and retinal oxygen saturation will be measured with the Dynamic Vessel Analyzer system by Imedos at baseline, in the 4th week of simvastatin or placebo intake as well as 3, 7 and 14 days after the end of intake.

Conditions

Healthy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Intervention group

10 healthy subjects receiving at first simvastatin for 4 weeks, then crossover. Measurements will be done with the Dynamic Vessel Analyzer (DVA) and Laser Doppler Velocimetry (LDV).

Group Type: EXPERIMENTAL

Dynamic Vessel Analyzer (DVA)

Intervention Type: DEVICE

Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation

Laser Doppler Velocimetry (LDV)

Intervention Type: DEVICE

Measurement of red blood cell velocity in retinal vessels

Simvastatin

Intervention Type: DRUG

Simvastatin Ranbaxy (Basics GmbH, Leverkusen, Germany) Dosage: 40 mg per day for 4 weeks, ingested in the morning Route of administration: peroral

Placebo group

10 healthy subjects receiving at first placebo for 4 weeks, then crossover. Measurements will be done with the Dynamic Vessel Analyzer (DVA) and Laser Doppler Velocimetry (LDV).

Group Type: PLACEBO_COMPARATOR

Dynamic Vessel Analyzer (DVA)

Intervention Type: DEVICE

Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation

Laser Doppler Velocimetry (LDV)

Intervention Type: DEVICE

Measurement of red blood cell velocity in retinal vessels

Placebo

Intervention Type: OTHER

Placebo, once daily for 4 weeks

Interventions

Dynamic Vessel Analyzer (DVA)

Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation

Intervention Type: DEVICE

Laser Doppler Velocimetry (LDV)

Measurement of red blood cell velocity in retinal vessels

Intervention Type: DEVICE

Simvastatin

Simvastatin Ranbaxy (Basics GmbH, Leverkusen, Germany) Dosage: 40 mg per day for 4 weeks, ingested in the morning Route of administration: peroral

Intervention Type: DRUG

Placebo

Placebo, once daily for 4 weeks

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

Informed consent for participation

• Men and women aged between 18 and 45 years, non-smokers
• Body mass index between 15th and 85th percentile
• Normal findings in the medical history and physical examination unless the investigator considers an abnormality to be clinically irrelevant
• Normal laboratory values unless the investigator considers an abnormality to be clinically irrelevant
• Systolic blood pressure < 140 mmHg, diastolic blood pressure < 90 mmHg
• Normal ophthalmic findings, ametropia less than 6 diopters

Exclusion Criteria

• History or presence of ocular disease
• Ametropy ≥ 6 dpt
• Previous or current treatment with statins
• Treatment with any drug in the 3 weeks preceding the first study day
• Symptoms of a clinically relevant illness in the 3 weeks before the first study day
• Participation in a clinical trial in the 3 weeks preceding the first study day
• Blood donation during the 3 weeks preceding the first study day
• History or family history of epilepsy
• History or presence of myopathy, renal failure or elevation of creatine kinase (CK) above normal levels
• History or presence of hepatic dysfunction, including increase of liver enzymes
• Abuse of alcoholic beverages
• Pregnancy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Medical University of Vienna

OTHER

Sponsor Role: lead

Responsible Party

Gerhard Garhofer

Assoc. Prof. Dr.

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Department of Clinical Pharmacology, Medical University of Vienna

Vienna, , Austria

Countries

Austria

Other Identifiers

OPHT-240215

Identifier Type: -

Identifier Source: org_study_id