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Effect of Simvastatin Withdrawal on Ocular Endothelial Function

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ClinicalTrials.gov Identifier: NCT02533141
Recruitment Status : Not yet recruiting
First Posted : August 26, 2015
Last Update Posted : August 20, 2019
Sponsor:
Information provided by (Responsible Party):
Gerhard Garhofer, Medical University of Vienna

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

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 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
Estimated Study Start Date : October 2019
Estimated Primary Completion Date : September 2020
Estimated Study Completion Date : December 2020

Resource links provided by the National Library of Medicine

Drug Information available for: Simvastatin

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




Primary Outcome Measures :
  1. Flicker induced vasodilatation (DVA) [ Time Frame: 16 weeks ]

Secondary Outcome Measures :
  1. Retinal oxygen saturation (DVA) [ Time Frame: 16 weeks ]
  2. Red blood cell velocity (LDV) [ Time Frame: 16 weeks ]


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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02533141


Contacts
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Contact: Gerhard Garhöfer, MD 0043 1 40400 ext 29810 gerhard.garhoefer@meduniwien.ac.at

Locations
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Austria
Department of Clinical Pharmacology, Medical University of Vienna Not yet recruiting
Vienna, Austria, 1090
Contact: Gerhard Garhofer, MD    00431 40400 ext 29810    gerhard.garhoefer@meduniwien.ac.at   
Sponsors and Collaborators
Medical University of Vienna

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Responsible Party: Gerhard Garhofer, Assoc. Prof. Dr., Medical University of Vienna
ClinicalTrials.gov Identifier: NCT02533141     History of Changes
Other Study ID Numbers: OPHT-240215
First Posted: August 26, 2015    Key Record Dates
Last Update Posted: August 20, 2019
Last Verified: August 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Gerhard Garhofer, 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:
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Simvastatin
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors