Jervell and Lange Nielsen Syndrome
Conditions
Keywords
Long QT syndrome
Brief summary
This study will test the effect of diltiazem, a calcium channel blocking drug, on the QT interval in patients with Jervell and Lange-Nielsen syndrome. This will be a single IV dose and acute effects (within minutes) will be observed.
Detailed description
Subjects will be recruited by study personnel and will be scheduled for a single outpatient visit. If an implanted cardiac device (pacemaker or ICD) is in place, it will be interrogated to ensure no recent rhythm abnormalities. Just prior to administering diltiazem, an ECG and BP will be obtained. If baseline SBP is \< 100 mm Hg or DBP \< 60 mm Hg, the study will be terminated. A single dose of I.V. diltiazem (0.25 mg/kg over 2 minutes) will be administered with 12-lead ECG and BP obtained at 2, 5, 7, 10, 15 and 20 minutes. If at 10 minutes there has been no QT shortening, and the SBP is stable (\<20% drop from baseline and \> 100 mm Hg) a repeat dose (0.35 mg/kg) will be given at 15 minutes, with 12-lead ECG and BP obtained at 17, 20, 22, 25, 30 and 35 minutes. After 20 minutes (single dose) or 35 minutes (2 doses), the test will end and the subject will remain on continuous telemetry for 2 hours. Prior to discharge the IV will be removed. The primary analysis will be a repeated measures (paired) comparison of the QTc at baseline and following diltiazem.
Interventions
DRUGdiltiazem
IV diltiazem (0.25 mg/kg) will be given over 2 minutes, with ECG and blood pressure measurements at baseline, 2, 5, 7, 10, 15 and 20 minutes. If at 10 minutes there is no QT shortening, and blood pressure is stable, an additional dose (0.35 mg/kg) will be given with ECG and blood pressure measurements at 17, 20, 22, 25, 30 and 35 minutes.
Sponsors
Vanderbilt University Medical Center
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age greater than 18 years * Genetically confirmed diagnosis of Jervell and Lange-Nielsen syndrome * Able to provide written informed consent
Exclusion criteria
* Known hypersensitivity to diltiazem * Pregnancy * Congestive heart failure, angina, preexcitation, or chronic obstructive pulmonary disease * Sick sinus syndrome or atrioventricular block in the absence of a pacemaker/defibrillator * Any clinically significant ongoing medical or surgical condition that might jeopardize the subject's safety or interfere with the conduct of the study in the judgement of the investigator * Baseline systolic blood pressure less than 100 Hg or diastolic blood pressure less than 60 Hg
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| QT Interval | Baseline | QT interval (on 12-lead ECG) in ms |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Diltiazem IV diltiazem (0.25 mg/kg) will be given over 2 minutes. A second IV dose (0.35 mg/kg) may be given at 10 minutes.
diltiazem: IV diltiazem (0.25 mg/kg) will be given over 2 minutes, with ECG and blood pressure measurements at baseline, 2, 5, 7, 10, 15 and 20 minutes. If at 10 minutes there is no QT shortening, and blood pressure is stable, an additional dose (0.35 mg/kg) will be given with ECG and blood pressure measurements at 17, 20, 22, 25, 30 and 35 minutes. | 1 |
| Total | 1 |
Baseline characteristics
| Characteristic | Diltiazem |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 29 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 1 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 1 Participants |
| Region of Enrollment United States | 1 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 1 |
| other Total, other adverse events | 0 / 1 |
| serious Total, serious adverse events | 0 / 1 |
Outcome results
Primary
QT Interval
QT interval (on 12-lead ECG) in ms
Time frame: Baseline
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diltiazem | QT Interval | 623 ms |
Primary
QT Interval
QT interval (on 12-lead ECG) in ms
Time frame: 5 minutes
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Diltiazem | QT Interval | 570 ms |