Lung Stem Cell Transplant for Pulmonary Fibrosis

(HALT-IPF Trial)

Overseen By Jackson Pettee

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of North Carolina, Chapel Hill

Disqualifiers: Other ILD, Obstructive lung disease, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 4-8 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment using stem cells to help individuals with idiopathic pulmonary fibrosis (IPF), a lung disease that makes breathing difficult. The goal is to determine if these stem cells, taken from the patient's own lungs, can safely improve lung function. Participants will either receive the stem cell treatment (Autologous Lung Stem Cell Transplant) or continue with their usual care. The trial seeks individuals diagnosed with IPF who experience frequent breathing difficulties. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, all patients will continue to receive standard care for their condition, so it's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that Lung Spheroid Stem Cells (LSCs) might safely treat pulmonary fibrosis. Studies have found that patients handled these cells well, with no major safety issues. In earlier trials, patients received LSCs without any serious side effects linked to the treatment. This suggests that LSCs are likely safe for humans, at least at the doses tested so far. However, since this trial remains in its early stages, researchers are still learning about the full safety picture. More data will help confirm patient tolerance. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary fibrosis, which typically include medications like antifibrotic drugs to slow disease progression, the Lung Stem Cell (LSC) Transplant offers a regenerative approach. This treatment uses Lung Spheroid Stem Cells, which are derived from the patient's own lung tissue, aiming to repair and regenerate damaged lung tissue. Researchers are excited because this method not only targets the root cause of the disease but also has the potential to improve lung function and quality of life. Additionally, the treatment is delivered via infusion, which may allow for a more targeted and efficient healing process compared to traditional systemic treatments.

What evidence suggests that this treatment might be an effective treatment for pulmonary fibrosis?

Research has shown that using a person's own Lung Spheroid Stem Cells (LSCs) could be a breakthrough in treating idiopathic pulmonary fibrosis (IPF). One study found that these stem cells can safely and effectively repair lung tissue damaged by the disease. In this trial, participants will receive either a low dose or a high dose of LSCs, while others will receive usual care without LSC infusion. Stem cells help control the body's inflammation, which is crucial in managing pulmonary fibrosis. Early results suggest that using a patient's own cells lowers the risk of rejection and leads to better outcomes. This treatment aims to improve lung function and slow the disease's progression. ^{1 3 4 6 7}

Who Is on the Research Team?

Leonard Lobo, MD

Principal Investigator

University of North Carolina, Chapel Hill

Are You a Good Fit for This Trial?

This trial is for adults aged 50-80 with Idiopathic Pulmonary Fibrosis (IPF), able to perform a walking test, and have specific lung function measures. Excluded are those with other significant health issues like chronic heart failure, obstructive lung disease, certain infections or recent hospitalization due to IPF.

Inclusion Criteria

Your lung function test shows that your ability to transfer carbon monoxide is greater than 25% of what is expected.

My lung function tests show I breathe well enough.

My lung condition is confirmed as UIP without other causes.

Exclusion Criteria

My lung function tests have shown improvement over the last year.

I have a health issue that makes it hard for me to do certain physical tests.

I was hospitalized for a sudden worsening of my lung condition within the last 2 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive intravenous infusion of Lung Spheroid Stem Cells (LSCs) 4-8 weeks after pulmonary biopsies

4-8 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at months 0.5, 1, 3, 6, 9, 12, 18, and 24

What Are the Treatments Tested in This Trial?

Interventions

• Autologous Lung Stem Cell Transplant

Trial Overview The trial tests the safety and effectiveness of two doses of autologous Lung Spheroid Stem Cells (LSCs) in treating IPF. Patients' own cells will be used to grow LSCs which are then given back via IV infusion. Participants will either receive stem cells or standard care and will be monitored over two years.

How Is the Trial Designed?

Group I: Low Dose LSCs (cohort 1) n = 4 planned Experimental Treatment 1 Intervention

4-8 weeks following transbronchial biopsy, participants in this arm will receive 100 million Lung Spheroid Stem Cell (LSC) infusion.

Group II: High Dose LSCs (Cohort 2) n = 12 planned Experimental Treatment 1 Intervention

4-8 weeks following transbronchial biopsy, participants in this arm will receive 200 million LSC infusion.

Group III: Usual Care (Cohort 1) n = 2 planned Active Control 1 Intervention

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

Group IV: Usual Care (Cohort 2) n = 6 planned Active Control 1 Intervention

Patients will receive standard of care with no biopsy and no infusion. Placebo will not be used.

Who Is Running the Clinical Trial?

University of North Carolina, Chapel Hill

Lead Sponsor

Trials

1,588

Recruited

4,364,000+

North Carolina State University

Collaborator

Trials

38

Recruited

50,000+

Published Research Related to This Trial

The study demonstrates that allogeneic lung spheroid cells (LSCs) can effectively reduce inflammation and fibrosis in a rat model of pulmonary fibrosis, suggesting their potential as a therapeutic option.

Infusion of allogeneic LSCs was found to preserve lung health without causing significant immune rejection, indicating a promising safety profile for future human applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a Mismatched Rat Model of Pulmonary Fibrosis. Cores, J., Hensley, MT., Kinlaw, K., et al.[2023]

A new method to generate therapeutic lung progenitor cells from healthy adult lung tissues has been developed, allowing for the creation of three-dimensional lung spheroids that mimic the natural lung environment and contain a mix of lung stem cells and supporting cells.

In animal models, these lung spheroid cells showed significant therapeutic effects, such as reducing fibrosis and promoting blood vessel formation, outperforming traditional stem cells from adipose tissue, indicating their potential for treating severe lung diseases like pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adult Lung Spheroid Cells Contain Progenitor Cells and Mediate Regeneration in Rodents With Bleomycin-Induced Pulmonary Fibrosis. Henry, E., Cores, J., Hensley, MT., et al.[2018]

Transplanting autologous lung-derived mesenchymal stem cells (LMSCs) into sheep with emphysema showed promising results, as the treatment was well tolerated and led to increased lung tissue mass and perfusion after 4 weeks.

Histological analysis confirmed that the LMSCs contributed to tissue regeneration by increasing cellularity and extracellular matrix content, suggesting that this method could be a potential therapy for lung regeneration in emphysema.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous lung-derived mesenchymal stem cell transplantation in experimental emphysema. Ingenito, EP., Tsai, L., Murthy, S., et al.[2022]

Intratracheal transplantation of alveolar type II-like cells derived from induced pluripotent stem cells significantly reduces pulmonary fibrosis in a rat model, even after fibrosis has already developed.

This treatment improves lung structure and works by inhibiting key fibrotic markers, such as transforming growth factor-β and α-smooth muscle actin, suggesting a potential new therapeutic approach for idiopathic pulmonary fibrosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induced pluripotent stem cell-derived lung alveolar epithelial type II cells reduce damage in bleomycin-induced lung fibrosis. Alvarez-Palomo, B., Sanchez-Lopez, LI., Moodley, Y., et al.[2021]

Lung spheroid cells, derived from fibrotic lungs and delivered via tail-vein injections, demonstrated safety and efficacy in treating pulmonary fibrosis in rat models, with a minimum effective dose identified as 3 × 10^6 human cells.

Histological analysis showed no signs of tumor formation or adverse immunological responses, indicating that lung spheroid cells could be a promising therapeutic option for idiopathic pulmonary fibrosis with potential for clinical application.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pre-investigational new drug study of lung spheroid cell therapy for treating pulmonary fibrosis. Cores, J., Dinh, PC., Hensley, T., et al.[2021]

Idiopathic pulmonary fibrosis currently has no effective pharmacological treatments to significantly improve survival, with lung transplantation being the only option, offering a 45% 5-year survival rate for advanced cases.

Initial clinical trials using mesenchymal stem cells for treatment have not shown convincing safety, but ongoing studies may help determine the best sources and delivery methods, while using stem cell-derived secretome could provide a safer alternative to direct cell transplantation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stem Cell-Based Therapy in Idiopathic Pulmonary Fibrosis. Barczyk, M., Schmidt, M., Mattoli, S.[2020]

The AETHER trial, involving 9 patients with mild to moderate idiopathic pulmonary fibrosis (IPF), demonstrated that a single intravenous infusion of human mesenchymal stem cells was safe, with no serious adverse events reported within 60 weeks.

While the treatment did not lead to significant improvements in lung function, as indicated by a 3.0% decline in forced vital capacity (FVC) and a 5.4% decline in lung diffusing capacity, the absence of treatment-related complications suggests potential for further exploration of this therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Allogeneic Human Mesenchymal Stem Cells in Patients With Idiopathic Pulmonary Fibrosis via Intravenous Delivery (AETHER): A Phase I Safety Clinical Trial. Glassberg, MK., Minkiewicz, J., Toonkel, RL., et al.[2018]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7308638/

A pre‐investigational new drug study of lung spheroid cell ... These data demonstrate the safety and efficacy of lung spheroid cells in their application as therapeutic agents for pulmonary fibrosis.

2. withpower.com withpower.com/trial/phase-1-idiopathic-pulmonary-fibrosis-9-2020-4643a?condition=pulmonary+fibrosis&ageList=65&overallStatus=Recruiting&hasNoPlacebo=false

Lung Stem Cell Transplant for Pulmonary Fibrosis Trial Overview The trial tests the safety and effectiveness of two doses of autologous Lung Spheroid Stem Cells (LSCs) in treating IPF. Patients' own cells ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10590845/

Pulmonary fibrosis: Is stem cell therapy the way forward? Stem cell therapy has emerged as a potential alternative treatment for pulmonary fibrosis, in which stem cells modulate the inflammatory response.

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04262167/human-autologous-lung-stem-cell-transplant-for-idiopathic-pulmonary-fibrosis

Human Autologous Lung Stem Cell Transplant for ... Purpose: To demonstrate the safety and efficacy of autologous Lung Spheroid Stem Cells (LSCs) administered by intravenous infusion in patients

5. stemcellres.biomedcentral.com stemcellres.biomedcentral.com/articles/10.1186/s13287-022-03181-8

Stem cell-based therapy for pulmonary fibrosis These data indicate that the BLM-injured alveolar epithelium can be functionally and durably repaired by the transplantation of hES-ATII cells.

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02745184

Clinical Efficacy and Safety of Autologous Lung Stem Cell ... After 24-week observation, the investigators will evaluate the safety and efficacy of the treatment by measuring the key clinical indicators. Official Title.

7. stemcellsjournals.onlinelibrary.wiley.com stemcellsjournals.onlinelibrary.wiley.com/doi/10.1002/sctm.16-0374

Safety and Efficacy of Allogeneic Lung Spheroid Cells in a ... We have demonstrated the safety and efficacy of allogeneic lung spheroid cell (LSC) treatment in attenuating the progression and severity of ...