Clinical trial NCT06461676: Study of Intramyocardial Injection of Ventrix Bio Extracellular Matrix (VentriGel) to Assess the Safety and Feasibility in Pediatric Patients with Hypoplastic Left Heart Syndrome (HLHS)
Official title: Study of Intramyocardial Injection of Ventrix Bio Extracellular Matrix (VentriGel) to Assess the Safety and Feasibility in Pediatric Patients with Hypoplastic Left Heart Syndrome (HLHS)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE1
Conditions: Hypoplastic Left Heart Syndrome
Keywords: Stage II Glenn operation
HLHS
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Ventrix, Inc.
name: University of California, San Diego
First posted: 2024-06-17
Enrollment: 12
Sex: ALL
Maximum age (years): 1
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The goal of this Phase I Open-Label study is to demonstrate the safety and feasibility of VentriGel injection in children with Hypoplastic Left Heart Syndrome (HLHS).

The main questions it aims to answer are:

* Whether VentriGel is safe in treating patients with HLHS
* Whether there are any preliminary improvements in measures of cardiac function following Ventrigel injection

Detailed description: HLHS, a type of congenital heart disease, presents a unique challenge where the left ventricle fails to develop, necessitating the right ventricle to manage both systemic and pulmonary blood flow. This condition, once fatal, has become manageable due to advancements in surgical techniques, with reported 5-year survival rates of 70-90%. However, these staged procedures, while lifesaving, can strain the right ventricle, leading to long-term issues such as weakened muscle and reduced cardiac function. Additionally, even with surgical intervention, patients often face a diminished quality of life.

Addressing these challenges, ongoing clinical trials explore regenerative therapies, particularly stem cell injections, aiming to improve heart function. Yet, concerns persist regarding the practicality and efficacy of these treatments, including issues with cell survival and coordination of injections within narrow timeframes.

Innovatively, the investigator and the team propose an alternative approach using VentriGel, an injectable hydrogel derived from decellularized porcine myocardium. Originally designed for treating heart failure post-myocardial infarction in adults, VentriGel has shown promising results in animal models, demonstrating significant improvements in cardiac function. Notably, its shelf-stable nature and flexible timing for administration offer advantages over traditional stem cell therapies.

Moreover, VentriGel's effectiveness in addressing right-ventricular failure, as demonstrated in recent studies, highlights its potential as a solution for HLHS patients. Leveraging approved extracellular matrix devices, such as Alloderm and SurgiSIS, further underscores the feasibility and safety of this approach, paving the way for potentially transformative treatments in congenital heart diseases.

Eligibility criteria: Inclusion Criteria:

* Subjects with Hypoplastic Left Heart Syndrome (HLHS) requiring Stage II Glenn operation under one year of age

Exclusion Criteria:

* Subjects undergoing the Stage II Glenn operations who do not have HLHS
* Subjects requiring mechanical circulatory support within 5 days pre pre-surgical intervention
* Parent or guardian unwilling or unable to comply with necessary follow-up(s)
* Immunosuppressive diseases or subjects who require treatment with interventions that cause immunosuppression
* A history of tumor or malignancy
* Coagulation disorders
* Chromosomal abnormalities that limit expected survival to \< 1 year
* Abnormal lab values that may increase the risk of the study procedure (WBC \>20,000 cells/ul or \< 1,000 cells/ul; platelet count \< 50,000 cells/ul; Hgb \< 8.0 gm/dl; LFTs \> 2x reference lab upper limit of normal) at the time of screening
* Subjects with conduction abnormalities, including atrioventricular block and bundle branch blocks
* Ventricular arrhythmias due to antiarrhythmic pharmacological therapy

Primary outcomes:
measure: Number of ventricular tachycardia events
timeFrame: upto 30 days post operation
measure: Number of Cardiogenic shock events
timeFrame: Day 1, 30 days post operation
measure: Number of unplanned cardiovascular operation events
timeFrame: 30 days post operation
measure: Number of patients requiring new permanent pacemaker
timeFrame: upto 30 days post operation
measure: Stroke or embolic event
timeFrame: upto 30 days post operation
measure: Number of Adverse Events
timeFrame: upto 30 days post operation
measure: Number of deaths
timeFrame: upto 30 days post operation
measure: Number of VentriGel products manufactured and delivered to subjects
timeFrame: 12 months
measure: Number of patients receiving Cardiac MRIs
timeFrame: Baseline, 6 months, 12 months
Secondary outcomes:
measure: Change in right ventricular ejection fraction
timeFrame: Baseline, 6 months, 12 months post operation
measure: Change in right ventricular end diastolic volume
timeFrame: Baseline, 6 months, 12 months post operation
measure: Change in right ventricular end systolic volume
timeFrame: Baseline, 6 months, 12 months post operation
measure: Change in tricuspid regurgitation
timeFrame: Baseline, 6 months,12 months post operation
measure: Change in right ventricular function Fractional Area Change
timeFrame: Baseline, 6 months,12 months post operation
measure: Change in right ventricular global longitudinal strain
timeFrame: Baseline, 6 months,12 months post operation
measure: Change in right ventricular global circumferential strain
timeFrame: Baseline, 6 months,12 months post operation
measure: Change in right ventricular Tricuspid Annular Plane Systolic Excursion (TAPSE)
timeFrame: Baseline, 6 months,12 months post operation
measure: Change in right atrial volume indexed
timeFrame: Baseline, 6 months,12 months post operation
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Altanta
state: Georgia
Study officials:
affiliation: Emory University
name: William Mahle, MD
role: PRINCIPAL_INVESTIGATOR
References: