Effect of Simvastatin Withdrawal on Ocular Endothelial Function

February 19, 2020 updated by: Gerhard Garhofer, Medical University of Vienna

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Study Type

Interventional

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Austria
      • Vienna, Austria, 1090
        • Department of Clinical Pharmacology, Medical University of Vienna

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 45 years (ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: BASIC_SCIENCE
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: DOUBLE

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Flicker induced vasodilatation (DVA)
Time Frame: 16 weeks
16 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
Retinal oxygen saturation (DVA)
Time Frame: 16 weeks
16 weeks
Red blood cell velocity (LDV)
Time Frame: 16 weeks
16 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Medical University of Vienna

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ANTICIPATED)

October 1, 2019

Primary Completion (ANTICIPATED)

September 1, 2020

Study Completion (ANTICIPATED)

December 1, 2020

Study Registration Dates

First Submitted

August 24, 2015

First Submitted That Met QC Criteria

August 25, 2015

First Posted (ESTIMATE)

August 26, 2015

Study Record Updates

Last Update Posted (ACTUAL)

February 20, 2020

Last Update Submitted That Met QC Criteria

February 19, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • OPHT-240215

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Healthy

Clinical Trials on Dynamic Vessel Analyzer (DVA)

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Rwanda

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe