Novel Form of Acquired Long QT Syndrome

The goal of this study is to determine whether anti-Ro/SSA antibodies are associated with acquired QT prolongation in subjects with connective tissue disease. The investigators will investigate whether gender or race influence correlation between anti-Ro antibody status and prolonged QT interval and the role of inflammatory cytokines in association with anti-Ro antibodies and QT prolongation. The investigators propose to add an additional objective to test whether QT prolongation is reversible with moderate doses of prednisone in patients with QT interval greater than 500 msec.

Study Overview

• Status: Recruiting
• Conditions: Connective Tissue Diseases; Rheumatoid Arthritis; Long QT Syndrome
• Intervention / Treatment: Drug: Prednisone

Detailed Description

There are two parts to this study. First, the investigators propose a prospective, observational study of subjects with connective tissue disease (CTD). Data on CTD diagnosis, disease activity, medications, electrolytes, anti-Ro Ab status, QT interval and serum for measurement of inflammatory markers and cytokines will be collected. Please see the research strategy for details of the protocol. The investigators expect that QTc prolongation will have a positive correlation with anti-Ro Ab positivity, elevated measures of inflammatory markers and higher levels of inflammatory cytokines, especially IL-6.

The second part of the study will include a subgroup of subjects who have QTc prolongation of more than 500 milliseconds. This is a proof of concept study to investigate whether immunosuppressive treatment with moderate dose of prednisone will reduce QTc in CTD patients exhibiting an excessive QTc prolongation of >500msec. Patients enrolled in the prospective observational study with QTc prolongation of more than 500 msec will receive oral prednisone 40mg daily for 3 days followed by 20mg for eleven days (a total of 2 weeks) with the goal to shorten or normalize the prolonged QTc. Other factors that may cause prolonged QTc will be evaluated and corrected as needed. Inflammatory markers, cytokines, and QTc will be measured at baseline and serially at days 3 and 14 (end of treatment). The investigators will monitor changes in QTc during three 24-hour periods during treatment at baseline, day 3 and day 14. Risks of prednisone include elevated serum glucose levels, edema, increased risk of infection and blood pressure elevation. The dosage and duration of prednisone used in this study is similar to that given for a severe allergic reaction. The PI will monitor the patients for potential side effects which will immediately be addressed.

• Study Type: Interventional
• Enrollment (Anticipated): 25
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Deana Lazaro, MD; Phone Number: 3198 7188366600; Email: deana.lazaro@va.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 11209
      • Recruiting
      • VA New York Harbor Healthcare System, NY and Brooklyn Campuses
      • Contact: Deana Lazaro, MD; Phone Number: 3198 718-836-6600; Email: deana.lazaro@va.gov

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 87 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

- Patients enrolled in New York Harbor Healthcare System with connective tissue disease

Exclusion Criteria:

• Atrial fibrillation
• Intraventricular conduction delay with wide QRS complex
• Acute medical conditions
• Drug overdose
• Hypothermia
• Known diagnosis or family history of hereditary Long QT syndrome, complete bundle brunch block, ventricular paced rhythm, profound bradycardia and tachycardia, and uncorrected hypothyroidism

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• 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: Prednisone Group; These patients have CTD and QTc over 500 msec. Prednisone is administered as a preventative measure against arrhythmia via QTc shortening.	Drug: Prednisone; We propose to test whether QT prolongation is reversible with moderate doses of prednisone in patients with QT interval greater than 500 msec.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Corrected QT Interval	QT interval to be measured on electrocardiogram	Baseline and at 14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Cytokine Levels	IL-1β, sTNFR1, TNFα, IL-10, IL-6, and α-interferon	Baseline and at 14 days
Change in ESR	Inflammatory Marker	Baseline and at 14 days
Change in CRP	Inflammatory Marker	Baseline and at 14 days

Collaborators and Investigators

• Sponsor: Narrows Institute for Biomedical Research
• Collaborators: VA New York Harbor Healthcare System

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2011
• Primary Completion (Anticipated): March 31, 2024
• Study Completion (Anticipated): September 30, 2024

Study Registration Dates

• First Submitted: November 14, 2019
• First Submitted That Met QC Criteria: November 15, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): April 11, 2022
• Last Update Submitted That Met QC Criteria: April 7, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: cytokines
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease; Congenital Abnormalities; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Defects, Congenital; Cardiovascular Abnormalities; Syndrome; Connective Tissue Diseases; Long QT Syndrome; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antineoplastic Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Prednisone
• Other Study ID Numbers: ORD01372

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: De-identified can be shared upon request. We do not anticipate the generation or development of any model organism or unique reagent from this study. If any new model organism or reagent is generated then we will make them available to other researchers upon request via the VA New York Harbor Healthcare System Technology Transfer office.
• IPD Sharing Time Frame: Data will be made available from the time of publication and will be kept for a minimum of 5 years.
• IPD Sharing Access Criteria: Data will be shared upon written request to the principal investigator.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF)

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.: Yes