Diltiazem in Jervell and Lange-Nielsen Syndrome

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.

Study Overview

• Status: Completed
• Conditions: Jervell and Lange Nielsen Syndrome
• Intervention / Treatment: Drug: diltiazem

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.

• Study Type: Interventional
• Enrollment (Actual): 1
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 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.	Drug: 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
QT Interval	QT interval (on 12-lead ECG) in ms	Baseline
QT Interval	QT interval (on 12-lead ECG) in ms	5 minutes

Collaborators and Investigators

• Sponsor: Vanderbilt University Medical Center
• Investigators: Principal Investigator: Prince J Kannankeril, MD, MSCI, Vanderbilt University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 16, 2024
• Primary Completion (Actual): October 23, 2024
• Study Completion (Actual): October 23, 2024

Study Registration Dates

• First Submitted: July 29, 2024
• First Submitted That Met QC Criteria: July 29, 2024
• First Posted (Actual): August 2, 2024

Study Record Updates

• Last Update Posted (Estimated): October 14, 2025
• Last Update Submitted That Met QC Criteria: September 24, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Long QT syndrome
• Additional Relevant MeSH Terms: Cardiac Conduction System Disease; Cardiovascular Diseases; Pathologic Processes; Heart Diseases; Arrhythmias, Cardiac; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathological Conditions, Signs and Symptoms; Long QT Syndrome; Jervell-Lange Nielsen Syndrome; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Benzazepines; Diltiazem
• Other Study ID Numbers: 240535

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual-level QT results will be published. Data obtained through this study may be provided to qualified researchers with no PHI included.
• IPD Sharing Time Frame: Data requests can be submitted immediately after article publication and the data will be made accessible for up to 36 months.
• IPD Sharing Access Criteria: Access may be requested by qualified researchers and will be provided following review and approval of a research proposal and execution of a Data Use Agreement.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No