Long QT SyndromeNCT02680080
Effect of Grapefruit on QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
A study testing Moxifloxacin and Grapefruit group in people with Long QT Syndrome, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 99 yearsHealthy volunteers can take part
- Conditions the study is for
- Long QT Syndrome
- What is being tested?
- Moxifloxacin and Grapefruit group
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteIsrael
- Study dates
- 1 Dec 2016to 22 May 2019
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 99 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Inclusions Criteria - healthy volunteers
- Healthy volunteers between 18 and <65 years of age.
- Subjects within BMI 18.0-29.0 calculated as Weight (Kg)/Height (m)2.
- No known history of significant neurological (including history of seizures or EEG abnormalities), renal, cardiovascular (including known structural cardiac abnormalities or hypertension), respiratory (asthma), endocrinological, gastrointestinal, hepatic or hematopoietic disease, neoplasm, psychological (marked anxiety, tension or agitation) or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications.
- No significant abnormalities in screening physical examination
- No known allergy to Fluoroquinolone (Moxifloxacin)
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- Subjects must provide written informed consent to participate in the study
- No significant abnormalities in the electrocardiogram prior to the first dosing day.
- Inclusions Criteria - LQTS patients:
- LQTS patients between 18 and <65 years of age.
- Subjects within BMI 18.0-29.0 calculated as Weight (Kg)/Height (m)2.
- No known history of significant neurological (including history of seizures or EEG abnormalities), renal, cardiovascular (including known structural cardiac abnormalities or hypertension), respiratory (asthma), endocrinological, gastrointestinal, hepatic or hematopoietic disease, neoplasm, psychological (marked anxiety, tension or agitation) or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications.
- No significant abnormalities in screening physical examination.
- Subjects must provide written informed consent to participate in the study.
Who cannot join
- Exclusions Criteria - healthy volunteers:
- Subjects with any clinically significant abnormality upon physical examination or in the clinical laboratory test values (CBC, electrolytes, renal function and liver enzymes).
- Subjects with a history of clinically defined GERD, peptic ulcer or any gastrointestinal surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of severe gastrointestinal narrowing, or frequent nausea or emesis, regardless of etiology.
- Subjects with significant allergic response to other drugs or history of food allergies deemed clinically significant or exclusionary for the study.
- Previous episode of syncope or seizures.
- Supine heart rate < 45 beats per minute after 5 minutes rest.
Show all 21Show fewer
- QTc prolongation (defined as QTc >450 msec for healthy volunteers) in the electrocardiogram on screening examination.
- Significant abnormalities in the electrocardiogram prior to the first dosing day. Patients with sinus arrhythmia will be excluded.
- Subjects with an inability to communicate well with the investigators and staff (i.e., language problem, poor mental development or impaired cerebral function).
- Subjects with any acute medical situation (e.g. acute infection) within 48 hours of study start, which is considered of significance by the Principal Investigator.
- Subjects who are non-cooperative or unwilling to sign consent form.
- Exclusions Criteria - LQTS patients:
- Subjects with any clinically significant abnormality upon physical examination or in the clinical laboratory test values (CBC, electrolytes, renal function and liver enzymes).
- Subjects with a history of clinically defined GERD, peptic ulcer or any gastrointestinal surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of severe gastrointestinal narrowing, or frequent nausea or emesis, regardless of etiology.
- Subjects with significant allergic response to other drugs or history of food allergies deemed clinically significant or exclusionary for the study.
- Previous episode of syncope or seizures.
- Supine heart rate < 45 beats per minute after 5 minutes rest.
- QTc prolongation (defined as QTc >500 msec for LQTS patients) in the electrocardiogram on screening examination.
- Subjects with an inability to communicate well with the investigators and staff (i.e., language problem, poor mental development or impaired cerebral function).
- Subjects with any acute medical situation (e.g. acute infection) within 48 hours of study start, which is considered of significance by the Principal Investigator.
- Subjects who are non-cooperative or unwilling to sign consent form.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Pink Grapefruit Juice on the QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
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
Read the 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
- Conditions
- Long QT Syndrome
- Being tested
- Moxifloxacin, Grapefruit group
- Medical subject headings
- Long QT Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MoxifloxacinDrug
a single 400 mg tablet of Moxifloxacin
Grapefruit groupDietary supplement
one liter of fresh pink-grapefruit juice
| Study group | Role | What they receive |
|---|---|---|
| Positive control group | Active comparator | subjects will receive a single 400 mg tablet of Moxifloxacin - the most commonly used positive control in "thorough" QTc (TQT) studies. Subjects will be continuously recorded by a Holter monitor for 24 hours Receives: Drug: Moxifloxacin |
| Grapefruit group | Active comparator | subjects will drink one liter of fresh pink-grapefruit juice as fast as possible. The pink-grapefruit juice will be squeezed in the morning of the experiment in the cardiology department. ECG will be performed immediately pre dose and at 1, 2, 3, 4, 6, 8, 12, 24 after fresh pink-grapefruit juice administration. In addition, subjects will be continuously recorded by a Holter monitor for 24 hours Receives: Dietary Supplement: Grapefruit group |
What is being measured
The primary outcome is the main question the study is designed to answer.
QT measurements
ECG will be performed after fresh pink-grapefruit juice administration. In addition, subjects will be continuously recorded by a Holter monitor for 24 hours QT interval, RR and QTc will be evaluated
Measured: up to 24 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2016 (estimated)
- Study start1 Dec 2016
- Primary completion12 Jun 2018
- Study completion22 May 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Long QT SyndromeStudies of the same condition, open and under way.
- More trials run by Tel-Aviv Sourasky Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tel-Aviv Sourasky Medical Center
- Sponsor type
- Other government
- Collaborators
- Tel Aviv Medical Center
- Responsible party
- Principal investigator, michal roll, Tel-Aviv Sourasky Medical Center
- Investigators
- Ehud Chorin, MD, Principal investigator, Tel Aviv MC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02680080
- Sponsor's protocol ID
- TASMC-15-EC-15-0728-TLV-CTIL
- Status last verified
- May 2019
- First submitted
- 28 Jan 2016
- Last updated
- 24 May 2019
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Chorin E, Hochstadt A, Granot Y, Khoury S, Schwartz AL, Margolis G, Barashi R, Viskin D, Ghantous E, Schnapper M, Mekori T, Fourey D, Guevara-Valdivia ME, Marquez MF, Zeltzer D, Rosso R, Viskin S. Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome. Heart Rhythm. 2019 Aug;16(8):1141-1148. doi: 10.1016/j.hrthm.2019.04.039. Epub 2019 May 8.
PubMed 31075442
Study at a glance
From the registry record, last updated by the sponsor on 24 May 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Pink Grapefruit Juice on the QT Interval in Healthy Volunteers and Patients With Congenital Long QT Syndrome
- ClinicalTrials.gov ID
- NCT02680080
- Acronym / sponsor ID
- TASMC-15-EC-15-0728-TLV-CTIL
- Conditions
- Long QT Syndrome
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Tel-Aviv Sourasky Medical CenterOther government
- Collaborators
- Tel Aviv Medical Center
- Study start
- 1 Dec 2016 (actual)
- Primary completion
- 12 Jun 2018 (actual)
- Study completion
- 22 May 2019 (actual)
- First posted
- 11 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Positive control group | Active comparator | Drug: Moxifloxacinsubjects will receive a single 400 mg tablet of Moxifloxacin - the most commonly used positive control in "thorough" QTc (TQT) studies. Subjects will be continuously recorded by a Holter monitor for 24 hours |
| Grapefruit group | Active comparator | Dietary Supplement: Grapefruit groupsubjects will drink one liter of fresh pink-grapefruit juice as fast as possible. The pink-grapefruit juice will be squeezed in the morning of the experiment in the cardiology department. ECG will be performed immediately pre dose and at 1, 2, 3, 4, 6, 8, 12, 24 after fresh pink-grapefruit juice administration. In addition, subjects will be continuously recorded by a Holter monitor for 24 hours |
Who may qualify
- Ages
- 18 to 99 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Inclusions Criteria - healthy volunteers
- Healthy volunteers between 18 and <65 years of age.
- Subjects within BMI 18.0-29.0 calculated as Weight (Kg)/Height (m)2.
- No known history of significant neurological (including history of seizures or EEG abnormalities), renal, cardiovascular (including known structural cardiac abnormalities or hypertension), respiratory (asthma), endocrinological, gastrointestinal, hepatic or hematopoietic disease, neoplasm, psychological (marked anxiety, tension or agitation) or any other clinically significant medical disorder, which in the investigator's judgment contraindicate administration of the study medications.
- No significant abnormalities in screening physical examination
Key exclusion criteria (21 listed)
- Subjects with any clinically significant abnormality upon physical examination or in the clinical laboratory test values (CBC, electrolytes, renal function and liver enzymes).
- Subjects with a history of clinically defined GERD, peptic ulcer or any gastrointestinal surgery other than appendectomy or herniotomy, or with any gastrointestinal disorder likely to influence drug absorption, or with any history of severe gastrointestinal narrowing, or frequent nausea or emesis, regardless of etiology.
- Subjects with significant allergic response to other drugs or history of food allergies deemed clinically significant or exclusionary for the study.
- Previous episode of syncope or seizures.
- Supine heart rate < 45 beats per minute after 5 minutes rest.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Moxifloxacina single 400 mg tablet of Moxifloxacin | Drug | Positive control group |
| Grapefruit groupone liter of fresh pink-grapefruit juice | Dietary supplement | Grapefruit group |
Primary outcome
QT measurements
Time frame: up to 24 hours
ECG will be performed after fresh pink-grapefruit juice administration. In addition, subjects will be continuously recorded by a Holter monitor for 24 hours QT interval, RR and QTc will be evaluated
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 May 2019.
- Derived from this study: PubMed 31075442Chorin E, Hochstadt A, Granot Y, Khoury S, Schwartz AL, Margolis G, Barashi R, Viskin D, Ghantous E, Schnapper M, Mekori T, Fourey D, Guevara-Valdivia ME, Marquez MF, Zeltzer D, Rosso R, Viskin S. Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome. Heart Rhythm. 2019 Aug;16(8):1141-1148. doi: 10.1016/j.hrthm.2019.04.039. Epub 2019 May 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Ehud Chorin, MD principal investigator
Tel Aviv MC
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Moxifloxacin and Grapefruit group in people with Long QT Syndrome, run by Tel-Aviv Sourasky Medical Center at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 24 May 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
QT measurements (time frame: up to 24 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02680080, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2019.