Effect of Simvastatin Withdrawal on Ocular Endothelial Function

Medical University of Vienna

Status and phase: Withdrawn; Phase 4

Conditions: Healthy

Treatments: Other: Placebo; Device: Laser Doppler Velocimetry (LDV); Drug: Simvastatin; Device: Dynamic Vessel Analyzer (DVA)

Study type: Interventional

Funder types: Other

Identifiers

NCT02533141

OPHT-240215

Details and patient eligibility

About

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.

Sex: All

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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0 participants in 2 patient groups, including a placebo group

Intervention group

Experimental group

Description:

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).

Treatment:

Drug: Simvastatin

Device: Laser Doppler Velocimetry (LDV)

Device: Dynamic Vessel Analyzer (DVA)

Placebo group

Placebo Comparator group

Description:

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).

Treatment:

Device: Laser Doppler Velocimetry (LDV)

Device: Dynamic Vessel Analyzer (DVA)

Other: Placebo