Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
Condition: Long QT Syndrome
MeSH terms: Long QT Syndrome; Syndrome
Study type: Interventional

Summary: 
      The list of medications that prolong the QT interval and can provoke torsade de pointes keeps
      expanding. This list includes not only antiarrhythmic drugs, but also medications with no
      cardiac indications. All these medications prolong the QT interval because they block a
      specific potassium channel on the myocardial cell membrane: the channel for the rapid
      component of the delayed rectifier potassium current or "IKr". The risk for developing
      torsade de pointes for patients taking any of the medications with IKr blockade capabilities
      varies from >4% for antiarrhythmic drugs to <0.01% for non-cardiac medications. The risk
      depends on the strength of IKr blockade, but also on specific patient characteristics. The
      majority of patients who develop torsade de pointes from non-cardiac medications have
      identifiable risk factors. In this regard, patients with a congenital long QT syndrome are
      prone to develop torsade de pointes when treated with QT-prolonging medications. This is
      because, due to their genetically defective ion channels, patients with Long QT Syndrome
      (LQTS) have impaired ventricular repolarization and reduced "repolarization reserve."
      Therefore, it is common medical practice to strongly advise patients with congenital LQTS to
      avoid all medications that have IKr channel blocker capabilities. it was reported that some
      flavonoids contained in pink-grapefruit juice block the IKr channel. These investigators also
      reported that drinking 1 liter of pink-grapefruit juice causes QT prolongation in healthy
      volunteers. The magnitude of the QT prolongation provoked by grapefruit juice was small
      However, drugs causing minor QT prolongation in healthy volunteers may provoke major QT
      prolongation in rare or sick individuals who are then at risk for developing torsade de
      pointes. Consequently, one could argue that, until proven otherwise, pink-grapefruit should
      be added to the list of "drugs" that are forbidden for patients with LQTS
    

Detailed description: 
      The list of medications that prolong the QT interval and can provoke torsade de pointes keeps
      expanding. This list includes not only antiarrhythmic drugs, but also medications with no
      cardiac indications (like several antibiotics, antihistamines or antipsychotic medications).
      All these medications prolong the QT interval because they block a specific potassium channel
      on the myocardial cell membrane: the channel for the rapid component of the delayed rectifier
      potassium current or "IKr". The risk for developing torsade de pointes for patients taking
      any of the medications with IKr blockade capabilities varies from >4% for antiarrhythmic
      drugs to <0.01% for non-cardiac medications. The risk depends on the strength of IKr
      blockade, but also on specific patient characteristics. In fact, the majority of patients who
      develop torsade de pointes from non-cardiac medications have identifiable risk factors. In
      this regard, patients with a congenital long QT syndrome (LQTS) are prone to develop torsade
      de pointes when treated with QT-prolonging medications. This is because, due to their
      genetically defective ion channels, patients with LQTS have impaired ventricular
      repolarization and reduced "repolarization reserve." Therefore, it is common medical practice
      to strongly advise patients with congenital LQTS to avoid all medications that have IKr
      channel blocker capabilities. Zitron et al reported that some flavonoids contained in
      pink-grapefruit juice block the IKr channel. These investigators also reported that drinking
      1 liter of pink-grapefruit juice causes QT prolongation in healthy volunteers. The magnitude
      of the QT prolongation provoked by grapefruit juice was small (12.5 ± 4.2 msec). However,
      drugs causing minor QT prolongation in healthy volunteers may provoke major QT prolongation
      in rare or sick individuals who are then at risk for developing torsade de pointes.
      Consequently, one could argue that, until proven otherwise, pink-grapefruit should be added
      to the list of "drugs" that are forbidden for patients with LQTS.

      This is a single center, open-label, randomized, crossover study. Subjects will be admitted
      to the cardiology department on the day before the first dose and will remain there until
      study completion. After performing a baseline electrocardiogram and baseline blood tests
      (Complete Blood Count, chemistry - up to 10 ml of blood) subjects will be continuously
      recorded by a Holter monitor for 24 hours (baseline Holter). On the next day subjects will be
      randomly divided into two experimental therapies (one after the other in a random order to
      the same group of patients
    

Intervention name(s): Moxifloxacin; Grapefruit group
Intervention type(s): Drug; Dietary Supplement
Intervention description(s): a single 400 mg tablet of Moxifloxacin; one liter of fresh pink-grapefruit juice
Intervention MeSH terms: Moxifloxacin
Allocation: Non-Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Primary purpose: Diagnostic