Effect of Simvastatin Withdrawal on Ocular Endothelial Function

Sponsor

Medical University of Vienna (Other)

Overall Status

Withdrawn

CT.gov ID

NCT02533141

Collaborator

(none)

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Healthy	Device: Dynamic Vessel Analyzer (DVA) Device: Laser Doppler Velocimetry (LDV) Drug: Simvastatin Other: Placebo	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Masking:

Double (Participant, Investigator)

Primary Purpose:

Basic Science

Official Title:

Effect of Simvastatin Withdrawal on Ocular Endothelial Function

Anticipated Study Start Date :

Oct 1, 2019

Anticipated Primary Completion Date :

Sep 1, 2020

Anticipated Study Completion Date :

Dec 1, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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).	Device: Dynamic Vessel Analyzer (DVA) Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation Device: 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
Placebo Comparator: 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).	Device: Dynamic Vessel Analyzer (DVA) Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation Device: Laser Doppler Velocimetry (LDV) Measurement of red blood cell velocity in retinal vessels Other: Placebo Placebo, once daily for 4 weeks

Arm

Intervention/Treatment

Experimental: 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).

Device: Dynamic Vessel Analyzer (DVA)

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

Device: 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

Placebo Comparator: 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).

Device: Dynamic Vessel Analyzer (DVA)

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

Device: Laser Doppler Velocimetry (LDV)

Measurement of red blood cell velocity in retinal vessels

Other: Placebo

Placebo, once daily for 4 weeks

Outcome Measures

Primary Outcome Measures

Flicker induced vasodilatation (DVA) [16 weeks]

Secondary Outcome Measures

Retinal oxygen saturation (DVA) [16 weeks]
Red blood cell velocity (LDV) [16 weeks]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 45 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Department of Clinical Pharmacology, Medical University of Vienna	Vienna		Austria	1090

Sponsors and Collaborators

Medical University of Vienna

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Gerhard Garhofer, Assoc. Prof. Dr., Medical University of Vienna

ClinicalTrials.gov Identifier:

NCT02533141

Other Study ID Numbers:

OPHT-240215

First Posted:

Aug 26, 2015

Last Update Posted:

Feb 20, 2020

Last Verified:

Feb 1, 2020

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Gerhard Garhofer, Assoc. Prof. Dr., Medical University of Vienna

Investigation of the changes of flicker induced vasodilatation before, during and after withdrawal of therapy with simvastatin

Additional relevant MeSH terms:

Simvastatin

Study Results

No Results Posted as of Feb 20, 2020