Cell Therapy for Swallowing Disorders

Overseen By Nogah Nativ, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Peter Belafsky, MD

Must not be taking: Corticosteroids, Immunosuppressants, Antibiotics, others

Disqualifiers: Neuromuscular disorders, Obesity, Diabetes, others

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

Compensation: Varies

Number of Visits: 4

Duration: 1 day

18 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to evaluate the safety of Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) during the 12 months following treatment of tongue dysphagia in male and female patients who have undergone surgery and/or chemo- and/or radiotherapy for squamous cell cancer of the oropharynx.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to maintain your current treatment regimen for existing conservative therapy, like swallowing therapy.

Will I have to stop taking my current medications?

The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to maintain your current treatment regimen for existing conservative therapy, like swallowing therapy.

What data supports the idea that Cell Therapy for Swallowing Disorders is an effective treatment?

The available research shows that cell therapy has been effective in other related conditions. For example, studies have shown that muscle-derived cells can help restore function in cases of urinary sphincter issues, which are similar in nature to swallowing disorders. Additionally, bone marrow-derived cells have been shown to aid in the regeneration of damaged intestinal tissue. These findings suggest that similar cell therapies could be effective for swallowing disorders by helping repair and regenerate the necessary muscle tissues. ^{1 2 3 4 5}

What data supports the effectiveness of the treatment Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) for swallowing disorders?

Research shows that muscle-derived cells have been effective in repairing sphincter function in urinary incontinence and urethral sphincter issues, suggesting potential for similar benefits in gastrointestinal repair. Additionally, bone marrow-derived cells have shown promise in regenerating damaged intestinal tissue, indicating that cell-based therapies can aid in gastrointestinal healing. ^{1 2 3 4 5}

What safety data exists for cell therapy in swallowing disorders?

The study titled 'Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer' evaluates the safety and potential efficacy of autologous muscle-derived cells (AMDCs) for treating swallowing impairment. Additionally, the study 'Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia' examines the safety and efficacy of human muscle-derived stem cell implantation in a mouse model. These studies provide some safety data for the use of muscle-derived cells in treating swallowing disorders. ^{6 7 8 9 10}

Is cell therapy for swallowing disorders safe for humans?

Research on autologous muscle-derived cells (AMDCs) for swallowing impairment in head and neck cancer patients suggests that this cell therapy is being evaluated for safety, but specific safety outcomes are not detailed in the available studies. Other studies on similar therapies in animal models indicate potential for safe integration and functional restoration, but human-specific safety data is limited. ^{6 7 8 9 10}

Is the treatment AMDC-GIR a promising treatment for swallowing disorders?

Yes, AMDC-GIR is a promising treatment for swallowing disorders. It uses muscle-derived cells to help repair and improve swallowing function, which is important for people who have trouble swallowing, especially after treatments like those for head and neck cancer. This approach aims to restore the ability to swallow safely and effectively. ^{2 3 6 9 11}

How is the treatment AMDC-GIR different from other treatments for swallowing disorders?

AMDC-GIR is unique because it uses the patient's own muscle cells to help repair and restore function in the gastrointestinal tract, which is different from traditional treatments that may not involve cell therapy. This approach aims to regenerate damaged tissues, offering a novel way to address swallowing disorders. ^{2 3 6 9 11}

Research Team

Peter Belafsky, MD

Principal Investigator

University of California Davis, Department of Otolaryngology

Maggie Kuhn, MD

Principal Investigator

University of California Davis, Department of Otolaryngology

Nogah Nativ, PhD

Principal Investigator

University of California Davis, Department of Otolaryngology

Eligibility Criteria

This trial is for adults who have moderate tongue dysphagia after treatment for oropharyngeal cancer and haven't improved with standard therapies. They must be at least 2 years post-treatment, disease-free, and able to report medical history. Excluded are those with recent participation in other trials, cell therapy for TD, certain health conditions like severe fibrosis or obesity, uncontrolled diabetes, bleeding disorders, allergies to specific drugs or proteins used in the study.

Inclusion Criteria

I can eat solid foods without special preparation.

My symptoms did not improve after trying standard treatments.

I am over 18, had treatment for throat cancer over 2 years ago, and have trouble swallowing without cancer returning.

Exclusion Criteria

I need antibiotics regularly to prevent infections or have needed multiple antibiotic treatments recently.

Simultaneously participating in another investigational drug or device study or has completed the follow-up phase for the primary endpoint of any previous study less than 30 days prior to the first evaluation in this study.

I have not been part of a trial for TD treatment in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single intramuscular injection of AMDC-GIR

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Visits at 3, 6, 12, and 24 months; follow-up calls at 1-2 days, 1 week, 15, 18, and 21 months

Treatment Details

Interventions

• Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR)

Trial Overview The trial tests the safety of AMDC-GIR cells injected into patients' tongues to treat swallowing difficulties over a year. Participants have had surgery/chemo/radiotherapy for squamous cell carcinoma but still struggle with swallowing (tongue dysphagia) despite conventional treatments.

Participant Groups

Group I: 300 x 106 dosage Experimental Treatment 1 Intervention

10 subjects will be receiving a dosage of 300 x 106 AMDC-GIR

Group II: 150 x 106 dosage Experimental Treatment 1 Intervention

10 subjects will be receiving a dosage of 150 x 106 AMDC-GIR

Who Is Running the Clinical Trial?

Peter Belafsky, MD

Lead Sponsor

Trials

2

Recruited

20+

Cook MyoSite

Industry Sponsor

Trials

14

Recruited

1,100+

Findings from Research

Bone marrow-derived cells (BMDCs) can successfully differentiate into intestinal epithelial cells long-term in chimeric mice, demonstrating their potential role in intestinal regeneration without special treatment.

In a study involving 40 irradiated C57BL/6 mice, 93.3% survival was observed one week post-transplantation, and BMDCs were found to express epithelial markers, indicating their successful engraftment and differentiation into various intestinal cell types.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term repopulation effects of donor BMDCs on intestinal epithelium. Liu, D., Wang, F., Zou, Z., et al.[2021]

Bone marrow-derived stem cells show promise as a potential therapy for gastrointestinal injuries, including those caused by radiation and inflammatory bowel disease, by helping to regenerate damaged tissues.

Despite the encouraging results from studies indicating that these stem cells can differentiate into functional epithelial cells, practical application in human patients remains challenging.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Present status and perspectives of stem cell-based therapies for gastrointestinal diseases. Yan, L., Cai, C., Li, J., et al.[2021]

Injecting allogenic muscle-derived cells (MDCs) into the urethra of rats with intrinsic sphincter deficiency significantly improved sphincter function, as indicated by increased leak point pressures (LPPs) over 6 weeks.

The MDCs successfully integrated into the striated muscle layer of the urethra without affecting bladder function, suggesting a promising new treatment approach for sphincter dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency. Chermansky, CJ., Tarin, T., Kwon, DD., et al.[2007]

The study found that autologous muscle-derived cells for urinary sphincter repair (AMDC-USR) were safe and well-tolerated, with no serious adverse events reported among female subjects with stress urinary incontinence.

Although the primary efficacy results were inconclusive due to a high placebo response rate (90%), post hoc analyses indicated that stricter endpoints might reveal a potential treatment effect, suggesting the need for refined trial designs in future studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. Jankowski, RJ., Tu, LM., Carlson, C., et al.[2021]

The research focuses on developing a cell therapy using muscle precursor cells (MPC) to treat urethral sphincter insufficiency, which involves a series of studies to understand muscle regeneration and cell extraction methods.

An animal model was created to mimic human sphincter injuries, allowing for the investigation of how transplanted MPCs interact with the peripheral nervous system, which is crucial for effective treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Cell therapy for urethral sphincter incompetence by muscle precursor cell autograft]. Yiou, R., Zini, L., Lecoeur, C., et al.[2006]

The phase I clinical trial involving 10 male oropharynx cancer survivors showed that injecting 150 million autologous muscle-derived cells (AMDCs) into the tongue is safe, with no serious adverse events reported over 24 months.

Participants experienced a significant increase in tongue pressure, suggesting improved muscle strength, although other measures of swallowing function did not show significant changes, indicating the need for further research in a larger, controlled trial.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer. Nativ-Zeltzer, N., Kuhn, MA., Evangelista, L., et al.[2023]

This study successfully bioengineered 3D human pyloric sphincter and small intestinal constructs that mimic the contractile behavior of natural smooth muscle cells, which is crucial for understanding gastrointestinal motility disorders.

The pyloric constructs exhibited tonic characteristics and responded to stimuli like potassium chloride and acetylcholine, making them valuable models for studying motility disorders and potential tissue replacements in the gastrointestinal tract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bioengineering functional human sphincteric and non-sphincteric gastrointestinal smooth muscle constructs. Rego, SL., Zakhem, E., Orlando, G., et al.[2018]

Transplanting interstitial cells of Cajal (ICCs) and neural progenitor cells (NPCs) into a chemically treated dysfunctional rat pylorus led to significant restoration of neuromuscular function, with 82% recovery of contraction and 83% recovery of relaxation, indicating effective cell integration and functionality restoration.

The combination of ICCs and NPCs resulted in greater neuronal differentiation and functional improvement compared to NPCs alone, suggesting that co-transplantation may be a promising strategy for treating pyloric dysfunction and related neurodegenerative disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional restoration of ex vivo model of pylorus: Co-injection of neural progenitor cells and interstitial cells of Cajal. Dadhich, P., Bitar, KN.[2021]

Human muscle-derived stem cells (MDSCs) showed over 100% survival after 12 weeks when implanted in a mouse model with tongue damage, indicating their potential for regenerative therapy.

Mice that received MDSC injections after tongue surgery experienced significantly greater weight gain compared to control groups, suggesting that MDSCs may improve recovery and function in cases of dysphagia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia. Kuhn, MA., Black, AB., Siddiqui, MT., et al.[2018]

Gastrointestinal motility disorders like achalasia and gastroparesis are linked to damage in nitrergic neurons, leading to severe digestive issues.

Stem cell therapy shows promise as a potential treatment to replace lost neurons and restore gut motility, but significant challenges remain before it can be widely implemented in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Upper Gastrointestinal Motility, Disease and Potential of Stem Cell Therapy. Gardner-Russell, J., Kuriakose, J., Hao, MM., et al.[2023]

The study successfully established a unilateral tongue atrophy model in rabbits by cutting the hypoglossal nerve, allowing for the evaluation of muscle changes after nerve injury.

Injecting adipose-derived stem cells (ADSCs) mixed with fat tissue into the denervated tongue significantly improved muscle fiber size and thickness compared to control groups, indicating potential for muscle regeneration and restoration of swallowing function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and feasibility of fat injection therapy with adipose-derived stem cells in a rabbit hypoglossal nerve paralysis model: A pilot study. Wada, A., Nishio, N., Yokoi, S., et al.[2021]

References

1. United States pubmed.ncbi.nlm.nih.gov

Long-term repopulation effects of donor BMDCs on intestinal epithelium. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Present status and perspectives of stem cell-based therapies for gastrointestinal diseases. [2021]

3. United States pubmed.ncbi.nlm.nih.gov

Intraurethral muscle-derived cell injections increase leak point pressure in a rat model of intrinsic sphincter deficiency. [2007]

4. Netherlands pubmed.ncbi.nlm.nih.gov

A double-blind, randomized, placebo-controlled clinical trial evaluating the safety and efficacy of autologous muscle derived cells in female subjects with stress urinary incontinence. [2021]

5. France pubmed.ncbi.nlm.nih.gov

[Cell therapy for urethral sphincter incompetence by muscle precursor cell autograft]. [2006]

6. United States pubmed.ncbi.nlm.nih.gov

Autologous Muscle-Derived Cell Therapy for Swallowing Impairment in Patients Following Treatment for Head and Neck Cancer. [2023]

7. United States pubmed.ncbi.nlm.nih.gov

Bioengineering functional human sphincteric and non-sphincteric gastrointestinal smooth muscle constructs. [2018]

8. England pubmed.ncbi.nlm.nih.gov

Functional restoration of ex vivo model of pylorus: Co-injection of neural progenitor cells and interstitial cells of Cajal. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Novel murine xenograft model for the evaluation of stem cell therapy for profound dysphagia. [2018]

10. United States pubmed.ncbi.nlm.nih.gov

Upper Gastrointestinal Motility, Disease and Potential of Stem Cell Therapy. [2023]

11. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and feasibility of fat injection therapy with adipose-derived stem cells in a rabbit hypoglossal nerve paralysis model: A pilot study. [2021]