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

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Flicker induced vasodilatation (DVA)
Time Frame: 16 weeks
16 weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2019

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 1, 2020

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 1, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
August 24, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
August 25, 2015

First Posted (ESTIMATE)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
August 26, 2015

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
February 20, 2020

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 19, 2020

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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.

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