Autologous Muscle Derived Cells for Swallowing Disorders

(REVIVE Trial)

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called AMDC-GIR (Autologous Muscle Derived Cells for Gastro-Intestinal Repair) to assist individuals who struggle with swallowing after throat cancer treatment. The primary goal is to assess the treatment's safety and its effects on tongue dysphagia (difficulty swallowing). Participants will receive either two treatments or a placebo, spaced a few weeks apart. The trial seeks individuals who have undergone surgery or therapy for throat cancer, continue to experience swallowing difficulties, and have not found relief with other treatments. As a Phase 1/Phase 2 trial, this research aims to understand how the treatment works in people and to measure its effectiveness in an initial, smaller group.

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.

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

Research has shown that using Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) appears safe for treating swallowing issues. Early results from past studies indicated that injecting these cells into the tongue is safe and may improve tongue function. In these studies, patients received the same dose of 150 million cells as in current trials, and it was well-tolerated.

No major side effects have been reported, with no significant adverse events observed so far. As these studies are in the early stages, they primarily focus on ensuring the treatment's safety for people, and the results so far are promising. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike standard treatments for swallowing disorders, which often involve dietary changes, exercises, or surgery, Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) uses a novel approach that could revolutionize care. This treatment is unique because it involves using a patient’s own muscle cells to repair and strengthen gastrointestinal tissues. Researchers are particularly excited about its potential to directly target and heal the underlying muscular issues, rather than just managing symptoms. By harnessing the body’s own cells, AMDC-GIR could offer a more natural and potentially more effective solution for those struggling with swallowing disorders.

What evidence suggests that AMDC-GIR might be an effective treatment for swallowing disorders?

Research has shown that using Autologous Muscle Derived Cells for Gastro-Intestinal Repair (AMDC-GIR) could help treat swallowing problems. In this trial, one group of participants will receive two doses of 150 million AMDC-GIR cells injected into the tongue. Early results suggest this approach is safe and might improve swallowing difficulties, known as tongue dysphagia. Studies have found that participants experienced some improvement in their ability to swallow after the treatment. While more research is needed to confirm these results, the early data is promising for those considering this treatment. ^{1 2 3 4 5}

Who Is on the Research Team?

Johnathon D Anderson, PhD

Principal Investigator

University of California Davis, Department of Otolaryngology

Peter Belafsky, MD

Principal Investigator

University of California Davis, Department of Otolaryngology

Maggie Kuhn, MD

Principal Investigator

University of California Davis, Department of Otolaryngology

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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 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]

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]

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]

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]

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. alphaclinic.ucsf.edu alphaclinic.ucsf.edu/multi-center-double-blind-randomized-placebo-controlled-investigation-autologous-muscle-derived

A Multi-Center, Double-Blind, Randomized Placebo- ... The purpose of this double-blind, randomized, placebo-controlled, multicenter clinical trial is to evaluate the safety and efficacy of Autologous Muscle Derived ...