Effect of Simvastatin Withdrawal on Ocular Endothelial Function

Healthy Clinical Trial

Official title:

Effect of Simvastatin Withdrawal on Ocular Endothelial Function

Clinical Trial Details — Status: Withdrawn

Administrative data

• NCT number: NCT02533141
• Other study ID #: OPHT-240215
• Status: Withdrawn
• Phase: Phase 4
• Start date: October 2019
• Est. completion date: December 2020

Study information

• Verified date: February 2020
• Source: Medical University of Vienna
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Withdrawn
• Enrollment: 0
• Est. completion date: December 2020
• Est. primary completion date: September 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 45 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy

Intervention

Device:
• Dynamic Vessel Analyzer (DVA)
Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation
• Laser Doppler Velocimetry (LDV)
Measurement of red blood cell velocity in retinal vessels

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

Other:
• Placebo
Placebo, once daily for 4 weeks

Locations

Country	Name	City	State
Austria	Department of Clinical Pharmacology, Medical University of Vienna	Vienna

Sponsors (1)

Lead Sponsor	Collaborator
Medical University of Vienna

Country where clinical trial is conducted

Austria, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Flicker induced vasodilatation (DVA)		16 weeks
Secondary	Retinal oxygen saturation (DVA)		16 weeks
Secondary	Red blood cell velocity (LDV)		16 weeks