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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new cell therapy called Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) to assist individuals with swallowing difficulties, known as tongue dysphagia, after throat cancer treatment. Researchers aim to determine the therapy's safety and effectiveness at two different doses. Individuals who have tried other treatments but still experience moderate swallowing issues after recovering from throat cancer may be suitable candidates. 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.

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.

Is there any evidence suggesting that Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) is likely to be safe for humans?

Research has shown that using one's own muscle cells, known as Autologous Muscle Derived Cells, for repairing the digestive system appears safe for treating swallowing problems. Early results from past studies suggest that injecting these cells, particularly at a specific dose, is generally well-tolerated. These studies did not identify any serious side effects related to the treatment, indicating a positive early sign of safety. However, as this trial is in its early stages, the primary focus remains on assessing safety. While initial results are promising, further research will provide a clearer understanding of its safety. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) is unique because it uses the patient's own muscle cells to help repair and regenerate tissues involved in swallowing. Unlike traditional treatments for swallowing disorders, which often focus on symptom management or involve surgical interventions, AMDC-GIR aims to directly address the underlying tissue damage. Researchers are excited about this approach because it offers the potential for a more natural and lasting repair process, reducing the need for invasive procedures and providing a more personalized treatment option.

What evidence suggests that AMDC-GIR might be an effective treatment for tongue dysphagia?

Studies have shown that using a patient's own muscle cells, known as Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR), may aid swallowing problems after cancer treatment. Initial results suggest that injecting these cells into the tongue is safe and could improve swallowing for patients who have undergone surgery or radiation. In this trial, participants will receive different dosages of AMDC-GIR, with some receiving 150 million cells and others 300 million cells. Early findings from other studies indicate that 150 million cells might be beneficial. This treatment uses the patient's own muscle cells to repair and strengthen the tongue. While more research is needed, early results are promising for those with difficulty swallowing, known as tongue dysphagia. ^{1 2 3 4 6}

Who Is on the 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

Are You a Good Fit for This Trial?

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.

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.

Medical condition or disorder that may limit life expectancy or that may cause clinical investigation plan (CIP) deviations (e.g., unable to perform self-evaluations or accurately report medical history, symptoms, or data).

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02838316

Study Details | NCT02838316 | Autologous Muscle Derived ... 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05421689?term=Gastrointestinal%20Repair%20for%20Tongue%20Dysphagia&rank=2

Autologous Muscle Derived Cells for Treatment of Tongue ... Initial results of a Phase 1 open label trial suggest that 150 x 10⁶ AMDC-GIR for the treatment of TD is safe and may be efficacious. A Phase I/II placebo ...

3. clinicaltrials.ucsf.edu clinicaltrials.ucsf.edu/trial/NCT05421689

Autologous Muscle Derived Cells for Treatment of Tongue ... This double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety of AMDC-GIR during the 24 months following 2 ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8909914/

Autologous Muscle Derived Cell Therapy for Swallowing ... Results of this Phase I clinical trial demonstrate that injection of 150×106 autologous muscle derived cells into the tongue is safe and may improve tongue ...

5. clinicaltrial.be clinicaltrial.be/fr/details/26574?active_not_recruiting=1&completed=0&enrolling_by_invitation=1&only_active=0&only_eligible=0&only_recruiting=0&per_page=100

Autologous Muscle Derived Cells for Treatment of Tongue ... Initial results of a Phase 1 open label trial suggest that 150 x 10⁶ AMDC-GIR for the treatment of TD is safe and may be efficacious. A Phase I/ ...

6. clin.larvol.com clin.larvol.com/trial-detail/NCT02838316

Autologous Muscle Derived Cells for Gastro-Intestinal ... Study product-related Serious Adverse Events (SAEs), Evaluate the safety of AMDC-GIR following treatment of tongue dysphagia, 24 months ; Study product-related, ...