Study Stopped
no funding
Effect of Simvastatin Withdrawal on Ocular Endothelial Function
1 other identifier
interventional
N/A
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
Started Oct 2019
Typical duration for phase_4 healthy
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
August 24, 2015
CompletedFirst Posted
Study publicly available on registry
August 26, 2015
CompletedStudy Start
First participant enrolled
October 1, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2020
CompletedFebruary 20, 2020
February 1, 2020
11 months
August 24, 2015
February 19, 2020
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Flicker induced vasodilatation (DVA)
16 weeks
Secondary Outcomes (2)
Retinal oxygen saturation (DVA)
16 weeks
Red blood cell velocity (LDV)
16 weeks
Study Arms (2)
Intervention group
EXPERIMENTAL10 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).
Placebo group
PLACEBO COMPARATOR10 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).
Interventions
Measurement of flicker induced vasodilatation, retinal vessel diameters and oxygen saturation
Measurement of red blood cell velocity in retinal vessels
Simvastatin Ranbaxy (Basics GmbH, Leverkusen, Germany) Dosage: 40 mg per day for 4 weeks, ingested in the morning Route of administration: peroral
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Department of Clinical Pharmacology, Medical University of Vienna
Vienna, 1090, Austria
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Assoc. Prof. Dr.
Study Record Dates
First Submitted
August 24, 2015
First Posted
August 26, 2015
Study Start
October 1, 2019
Primary Completion
September 1, 2020
Study Completion
December 1, 2020
Last Updated
February 20, 2020
Record last verified: 2020-02