Gene and Cell Therapy for Heart Attack

(ENACT-AMI Trial)

Not currently recruiting at 3 trial locations

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Ottawa Hospital Research Institute

Must not be taking: Immunosuppressants

Disqualifiers: HIV, Hepatitis B/C, Malignancy, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 4

Duration: 1 day

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new gene and cell therapy to treat heart attack damage. The aim is to boost the heart's recovery by enhancing special cells, called progenitor cells, with a gene that helps blood flow. Participants will receive one of three treatments: a placebo, regular progenitor cells (Autologous EPCs), or enhanced progenitor cells (Autologous EPCs Transfected with human eNOS). This trial suits individuals who experienced a specific type of heart attack (anterior ST-elevation myocardial infarction) in the last 30 days and are stable after a stent procedure.

As a Phase 2 trial, this research measures the treatment's effectiveness in an initial, smaller group of people, offering participants a chance to contribute to groundbreaking heart recovery advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using a person's own endothelial progenitor cells (EPCs) is generally safe and might help repair heart tissue. In one study, these cells were tested in individuals with heart issues, and the results suggested they were both feasible and safe.

A newer method involves modifying these cells with human eNOS. Early research, such as the ENACT-AMI trial, is assessing the safety of this approach. Although this specific method is still under investigation, early results from similar treatments suggest safety. Both treatments are in a phase focused primarily on safety, with researchers closely monitoring participant reactions. Overall, current evidence suggests these treatments are safe, but ongoing studies are crucial for confirmation. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they introduce a novel approach to heart attack recovery by using the body's own cells. Unlike typical treatments, which often focus on medications like beta-blockers, ACE inhibitors, or angioplasty to manage heart attack symptoms and prevent further damage, these treatments involve injecting endothelial progenitor cells (EPCs) directly into the affected artery to potentially repair heart tissue. One treatment uses EPCs enhanced with human eNOS, an enzyme that helps produce nitric oxide, which can improve blood flow and boost the heart's health. This innovative method could lead to faster and more effective healing, offering new hope for heart attack patients.

What evidence suggests that this trial's treatments could be effective for heart attack?

In this trial, participants will receive one of the following treatments: Autologous EPCs, Autologous EPCs transfected with human eNOS, or a placebo comparator of Plasma-Lyte A and 25% autologous plasma. Previous studies have shown that using a person's own endothelial progenitor cells (EPCs) holds promise for treating heart conditions. These cells have been linked to improved heart function after a heart attack by aiding in the repair of damaged heart tissue. Research suggests they can support recovery and enhance heart performance over time.

For EPCs modified with a human gene called eNOS (endothelial nitric oxide synthase), early results are also promising. These modified cells have helped blood vessels grow and improved heart recovery. The eNOS gene enhances the cells' ability to repair heart damage and improve blood flow. Overall, both treatments show potential for improving heart health after a heart attack. ^{2 5 6 7 8}

Who Is on the Research Team?

Duncan Stewart, MD, FRCP C

Principal Investigator

Ottawa Hospital Research Institute

Are You a Good Fit for This Trial?

This trial is for adults aged 18-80 who've had a successful stent implantation after a heart attack within the last month, are stable, and have reduced heart function (LVEF ≤45%). Women must meet specific reproductive criteria. Exclusions include autoimmune disease treatment, significant heart issues unrelated to the recent attack, HIV or hepatitis B/C infection, non-compliance history, other investigational treatments currently or in the past.

Inclusion Criteria

Your heart's pumping function, measured by echocardiography, must not be too high.

My heart's pumping ability is good after a heart attack.

I had a heart attack in the last 30 days confirmed by an ECG.

Exclusion Criteria

Confirmed pregnant or lactating

I had heart muscle weakness before my major heart attack.

I have a serious heart valve problem that hasn't been fixed.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Apheresis and Randomization

Participants undergo apheresis and are randomized to treatment groups

1 week

1 visit (in-person)

Treatment

Participants receive the randomized treatment allocation via intracoronary injection

1 day

1 visit (in-person, overnight stay)

Post-Treatment Monitoring

Participants are monitored in hospital overnight for continuous cardiac monitoring

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

Clinic visits at 1 week, 1, 3, and 6 months

Long-term Follow-up

Registry to collect long-term safety information from telephone contacts

10 years

What Are the Treatments Tested in This Trial?

Interventions

• Autologous EPCs
• Autologous EPCs Transfected with human eNOS
• Plasma-Lyte A and 25% Autologous Plasma

Trial Overview The trial tests enhanced cell therapy for heart attack recovery by using patients' own cells. Some cells are modified with eNOS to improve their function. It's a combination of gene and cell therapy aimed at treating cardiac disease post-heart attack.

How Is the Trial Designed?

Group I: Autologous EPCs Transfected with human eNOS Experimental Treatment 1 Intervention

A single dose of 20 million Autologous transfected with human eNOS (endothelial nitric oxide synthase) Endothelial Progenitor Cells in Human Albumin 2.5% total = 8 mL of study product delivered into the Infarct Related Artery

Group II: Autologous EPCs Experimental Treatment 1 Intervention

A single dose of 20 million Autologous non-transfected Endothelial Progenitor Cells in Human Albumin 2.5% total = 8 mL of study product delivered into the Infarct Related Artery

Group III: Plasma-Lyte A and 25% autologous plasma Placebo Group 1 Intervention

A single dose of Plasma-Lyte A in Human Albumin 2.5% total = 8 mL of study product delivered into the Infarct Related Artery

Who Is Running the Clinical Trial?

Ottawa Hospital Research Institute

Lead Sponsor

Trials

585

Recruited

3,283,000+

Canadian Institutes of Health Research (CIHR)

Collaborator

Trials

1,417

Recruited

26,550,000+

Stem Cell Network

Collaborator

Trials

9

Recruited

600+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2276734/

Endothelial Progenitor Cells for Cardiovascular ... Freshly isolated (i.e., not cultured) CD34+ EPCs produced similar results in rats with acute myocardial infarction (Kocher et al. ... cells in myocardial ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10613116/

Prognostic Value of Endothelial Progenitor Cells in Acute ... Worse clinical outcomes in acute myocardial infarction patients with type 2 diabetes mellitus: relevance to impaired endothelial progenitor cells mobilization.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022480412004131

Effects on transplanted cell survival and autologous ... The present study was designed to investigate whether exogenous erythropoietin (EPO) delivery could improve the survival of transplanted EPCs and enhance the ...

4. ahajournals.org ahajournals.org/doi/10.1161/01.hyp.0000168923.92885.f7

Therapeutic Potential of Endothelial Progenitor Cells in ... The recently published final 1-year follow-up results for this phase I trial showed sustained improvement in left ventricular function, ...

5. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1465324916303802

Safety and efficacy of autologous thymosin β4 pre-treated ... Experimental studies and clinical trials suggest that endothelial progenitor cell (EPC) transplantation can repair “broken” heart.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4131276/

Endothelial progenitor cells in cardiovascular diseases PAD is associated with endothelial dysfunction but there have been limited and inconsistent data available on the number and functional capacity of EPCs in PAD.

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6312444/

Autologous Endothelial Progenitor Cells Transplantation for ... In this trial, we test the safety and feasibility of autologous transplantation of ex vivo expanded EPCs in patients with acute ischemic stroke.

8. isct-cytotherapy.org isct-cytotherapy.org/article/S1465-3249(16)30380-2/fulltext

Safety and efficacy of autologous thymosin β4 pre-treated ... Our pilot study suggested that Tβ4-optimized EPC transplantation appeared to be feasible and safe, and might have beneficial effects on exercise capacity and ...