Autologous Muscle Derived Cells for Swallowing Disorders

(REVIVE Trial)

Recruiting at 1 trial location

Overseen By Johnathon D Anderson, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: University of California, Davis

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

Disqualifiers: Neuromuscular disorders, Uncontrolled diabetes, Cancer, others

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

Compensation: Varies

Number of Visits: 3

Duration: 4-6 weeks

66 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety of AMDC-GIR during the 24 months following 2 consecutive treatments 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.

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 willing to maintain your current treatment regimen for existing therapies, like swallowing therapy.

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

Research shows that autologous muscle-derived cells have been effective in repairing urinary sphincters, which suggests they might help in repairing other muscle-related issues, like those involved in swallowing disorders. ^{1 2 3 4 5}

Is the use of autologous muscle-derived cells generally safe in humans?

Studies on autologous muscle-derived cells (AMDC) for various conditions, including swallowing impairment and urinary issues, have shown that the treatment is generally safe in humans, with no serious treatment-related adverse events reported. ^{2 3 4 6 7}

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 potentially repair and restore function in the gastrointestinal tract, which is different from traditional treatments that may not involve regenerative cell therapy. ^{1 2 5 6 8}

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

Johnathon D Anderson, PhD

Principal Investigator

University of California Davis, Department of Otolaryngology

Eligibility Criteria

This trial is for adults who have trouble swallowing (tongue dysphagia) after treatment for oropharyngeal cancer. They must be at least 18, finished with cancer treatment for over two years, and not responding to current therapies. People can't join if they've had recent other trials, uncontrolled diabetes, immune issues, certain allergies, active cancers besides skin cancer, or are pregnant.

Inclusion Criteria

My swallowing difficulty is moderate, and I can eat some or most foods.

I finished my treatment 2 years ago and have been disease-free since, confirmed by tests and doctor's exams.

I am 18 or older with throat dryness from treatment for throat cancer.

Exclusion Criteria

My doctor says my cancer is likely to come back or not go away.

I do not have a bleeding disorder that cannot be corrected.

I have a condition that could cause serious problems after surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive two treatments of intramuscular injection of AMDC-GIR or placebo spaced 4-6 weeks apart

4-6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 months

Multiple visits at 1-2 days, 1 week, 4 weeks, 3 months, 6 months, 12 months, 15 months, 18 months, 21 months, and 24 months

Open-label extension (optional)

Participants in the placebo group may opt to receive AMDC-GIR injections after unblinding

6 months post-injection

Treatment Details

Interventions

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

Trial Overview The study tests the safety of injecting one's own muscle cells (AMDC-GIR) into the tongue versus a placebo in improving swallowing difficulties. Participants will receive two treatments and be monitored over 24 months in this double-blind study where neither they nor the researchers know who gets which treatment.

Participant Groups

Group I: Experimental: 150 x 10⁶ AMDC-GIR dosage Experimental Treatment 1 Intervention

33 subjects will be receiving two doses of 150 x 10⁶ AMDC-GIR spaced 4-6 weeks apart.

Group II: Experimental: Identical Placebo composed of the same cryopreservation medium used for AMDC-GIR Placebo Group 1 Intervention

33 subjects will be receiving two doses of identical placebo composed of the same cryopreservation medium used for AMDC-GIR. Doses will be spaced 4-6 weeks apart.

Who Is Running the Clinical Trial?

University of California, Davis

Lead Sponsor

Trials

958

Recruited

4,816,000+

Cook MyoSite

Industry Sponsor

Trials

14

Recruited

1,100+

California Institute for Regenerative Medicine (CIRM)

Collaborator

Trials

70

Recruited

3,300+

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]

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]

In a study of 58 participants, both autologous muscle-derived cell (AMDC) injections and placebo injections led to significant increases in urethral sphincter volumes and reductions in stress incontinence episode frequency (IEF) after 12 months, but there were no significant differences between the two groups.

Factors such as longer urethral length and larger external sphincter volume at baseline were associated with better responses to AMDC injections, suggesting these may be important predictors of treatment efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. Ismail, S., Morin, M., Tu, LM.[2021]

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]

In a clinical trial involving 20 patients with underactive bladder (UAB), intradetrusor injections of Autologous Muscle Derived Cells (AMDC) showed promising safety and efficacy, with 58% of patients reporting significant improvement in symptoms at 12 months post-treatment.

No serious adverse events were reported, and improvements included reduced post-void residual urine volume and increased voiding efficiency, suggesting that AMDC therapy could be a viable option for patients with chronic urinary retention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder. Gilleran, J., Diokno, AC., Ward, E., et al.[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]

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

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

3. 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]

4. Germany pubmed.ncbi.nlm.nih.gov

Assessment of the effects of autologous muscle-derived cell injections on urethral sphincter morphometry using 3D/4D ultrasound. [2021]

5. England pubmed.ncbi.nlm.nih.gov

Acquisition of a gastric or duodenal phenotype on heterotropic transplantation of esophagus and bladder tissues in F344 rats. [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. Netherlands pubmed.ncbi.nlm.nih.gov

Improved global response outcome after intradetrusor injection of adult muscle-derived cells for the treatment of underactive bladder. [2021]

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

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