Bone Marrow Cells for Radiation-Induced Dry Mouth

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Disqualifiers: Salivary gland disease

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

Approved in 5 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new approach to address dry mouth caused by radiation treatment for head and neck cancer. Researchers aim to determine if injecting mesenchymal stem cells (MSCs) from a patient's own bone marrow into the salivary glands is safe and tolerable. The trial targets individuals who have undergone radiation treatment for head and neck cancer and now experience dry mouth affecting daily life. Participants will undergo procedures such as bone marrow collection, saliva donation, and salivary gland ultrasounds. This trial does not offer an expanded access program. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, providing participants the opportunity to be among the first to receive this innovative therapy.

Do I need to stop my current medications for this trial?

The trial protocol does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

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

Research has shown that mesenchymal stem cells (MSCs) are generally safe for humans. In past studies, patients who received MSCs for radiation-induced dry mouth experienced good safety outcomes. One study found that injecting MSCs from a person's own bone marrow did not cause serious side effects.

Another study examined MSCs from fat tissue and reported similar safety results, with no major long-term problems. These findings suggest that MSCs might safely treat radiation-induced dry mouth. However, as this trial is in an early stage, it primarily aims to confirm safety and tolerability, necessitating further research to fully understand any potential risks. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for radiation-induced dry mouth, which often focus on managing symptoms with saliva substitutes or medications like pilocarpine, mesenchymal stem cell (MSC) injections offer a unique approach by potentially repairing the damaged salivary glands themselves. MSCs are known for their regenerative capabilities and anti-inflammatory properties, which might help restore salivary function rather than just alleviate symptoms. Researchers are excited about this treatment because it represents a shift from palliative care to a potential cure, offering hope for long-term relief and improved quality of life for patients.

What evidence suggests that this treatment might be an effective treatment for radiation-induced dry mouth?

Research has shown that mesenchymal stem cells (MSCs), studied in this trial, might alleviate dry mouth caused by radiation therapy. These cells, taken from a patient's own bone marrow, could enhance salivary gland function. Early results from patients who underwent radiation for head and neck cancer suggest that MSCs can potentially treat this issue. Although further research is necessary, these initial findings offer hope for easing symptoms of radiation-induced dry mouth. ^{1 2 3 5 6}

Who Is on the Research Team?

Randall Kimple, MD, PhD

Principal Investigator

University of Wisconsin, Madison

Jacques Galipeau, MD

Principal Investigator

University of Wisconsin, Madison

Are You a Good Fit for This Trial?

This trial is for adults aged 18-90 with dry mouth after radiation therapy for head and neck cancer. They must be at least 2 years post-treatment, in good health (Karnofsky score ≥70), able to undergo bone marrow collection under local anesthesia, have no current cancer signs, and can consent.

Inclusion Criteria

I had head and neck cancer, was treated with radiation, and now show no signs of the disease.

Willing and able to give informed consent

I have dry mouth with less than 80% of my normal saliva production.

Exclusion Criteria

I have a condition affecting my salivary glands.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Bone Marrow Collection

Participants undergo a collection of bone marrow using a needle

1 day

1 visit (in-person)

MSC Injection

Injection of mesenchymal stem cells into salivary glands

1 day

1 visit (in-person)

Initial Follow-up

Participants are monitored for safety and tolerability, including pain and adverse events

1 month

Multiple visits (in-person)

Long-term Follow-up

Participants are monitored for changes in quality of life and salivary production

24 months

Visits at 3, 6, and 12 months (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• MSC

Trial Overview The study tests the safety of injecting mesenchymal stem cells (MSCs) from patients' own bone marrow into their salivary glands to treat dry mouth caused by radiation. It includes collecting bone marrow, donating saliva, ultrasound exams, and questionnaires over a period of up to 30 months.

How Is the Trial Designed?

Group I: Mesenchymal Stem Cell (MSC) injection Experimental Treatment 1 Intervention

MSC is already approved in United States, European Union, Canada, Japan, China for the following indications:

Approved in United States as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in European Union as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in Canada as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in Japan as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Approved in China as Mesenchymal Stem Cells for:

• Graft-versus-host disease
• Crohn's disease
• Multiple sclerosis
• Type 1 diabetes
• Cardiovascular diseases

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Published Research Related to This Trial

The MARSH trial is a first-in-human study assessing the safety and tolerability of bone marrow-derived mesenchymal stromal cells (BM-MSCs) activated by interferon-γ for treating radiation-induced xerostomia in head and neck cancer patients, involving 21 to 30 subjects.

This innovative therapy aims to restore salivary gland function and improve quality of life, potentially offering a curative option for xerostomia, which currently lacks effective treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): Study protocol for a phase 1 dose-escalation trial of patients with xerostomia after radiation therapy for head and neck cancer: MARSH: Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction. Blitzer, GC., Rogus-Pulia, NM., Mattison, RJ., et al.[2023]

This study will evaluate the safety and preliminary efficacy of allogeneic mesenchymal stromal stem cells (MSCs) from umbilical cord tissue in treating xerostomia in 10 oropharyngeal cancer patients who have experienced dry mouth after radiotherapy.

The innovative approach of using MSCs aims to improve salivary flow and quality of life for patients, with assessments planned for toxicity, salivary composition, and tissue characteristics over a 4-month period, potentially offering advantages over existing treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Post-radiation xerostomia therapy with allogeneic mesenchymal stromal stem cells in patients with head and neck cancer: study protocol for phase I clinical trial. Strojan, P., Plavc, G., Kokalj, M., et al.[2023]

This systematic review aims to evaluate the efficacy and safety of mesenchymal stem cell (MSC) therapy for treating salivary gland hypofunction caused by radiation injury, focusing on salivary flow rates as the primary outcome.

The review will analyze existing animal studies to provide insights into the effectiveness and safety of MSC treatment, which could help optimize future clinical trials for patients suffering from dry mouth after head and neck radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mesenchymal stromal/stem cell therapy for radiation-induced salivary gland hypofunction in animal models: a protocol for a systematic review and meta-analysis. Jansson, PM., Lynggaard, CD., Carlander, AF., et al.[2022]

Cell-derived vesicles (CDVs) from adipose-derived mesenchymal stem cells (ADMSCs) effectively restored the proliferation and function of irradiated salivary gland (SG) epithelial cells in vitro, indicating their potential as a radioprotective treatment.

The study showed that ADMSC-CDVs not only improved cell proliferation and amylase activity in irradiated SG cells but also restored transepithelial electrical resistance (TEER), suggesting a comprehensive protective effect against radiation damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cell-derived vesicles from adipose-derived mesenchymal stem cells ameliorate irradiation-induced salivary gland cell damage. Kim, JM., Choi, ME., Jeon, EJ., et al.[2022]

The study involving 30 patients with radiation-induced xerostomia showed that autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections are safe, with no serious adverse events linked to the treatment over a follow-up period of at least 2 years.

Patients receiving ASC therapy reported a significant reduction in xerostomia symptoms and a slight increase in saliva flow rates compared to the placebo group, indicating a clinically relevant benefit from the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term Safety of Treatment with Autologous Mesenchymal Stem Cells in Patients with Radiation-Induced Xerostomia: Primary Results of the MESRIX Phase I/II Randomized Trial. Lynggaard, CD., Grønhøj, C., Jensen, SB., et al.[2023]

Multipotent mesenchymal stromal cells (MSCs) show promising therapeutic effects for treating side effects of radiation, particularly in acute radiation reactions, based on a review of both experimental and clinical data.

MSCs can be administered either locally or systemically to irradiated organs and tissues, demonstrating protective and regenerative effects, with various mechanisms of action being explored.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic Effects of Multipotent Mesenchymal Stromal Cells after Irradiation]. Kalmykova, NV., Alexandrova, SA.[2018]

Adipose tissue-derived mesenchymal stromal cells (aMSCs) significantly reduced the duration of radiation-induced oral mucositis (RIOM) in a mouse model, with a 72% decrease in ulcer duration from 5.6 days to 1.6 days after treatment.

The effectiveness of aMSCs therapy was influenced by factors such as dose size, frequency, and timing of administration, and importantly, the treatment did not promote the growth of head and neck cancer cells in vitro.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adipose mesenchymal stromal cells minimize and repair radiation-induced oral mucositis. Maria, OM., Shalaby, M., Syme, A., et al.[2018]

The pilot study involving 6 patients with radiation-induced xerostomia showed that injecting autologous IFNγ-stimulated mesenchymal stromal/stem cells (MSC(M)) into the submandibular gland is safe, with no serious adverse events reported within a month after the injection.

There was a trend towards increased salivary production and improved quality of life in half of the patients, suggesting potential efficacy of MSC(M) treatment for alleviating dry mouth symptoms in head and neck cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Marrow-Derived Autologous Stromal Cells for the Restoration of Salivary Hypofunction (MARSH): A pilot, first-in-human study of interferon gamma-stimulated marrow mesenchymal stromal cells for treatment of radiation-induced xerostomia. Blitzer, GC., Glazer, T., Burr, A., et al.[2023]

Bone marrow-derived clonal mesenchymal stem cells (BM-cMSCs) significantly improved salivary flow rates in mice with irradiation-induced salivary gland damage, indicating their potential efficacy in treating xerostomia.

The study demonstrated that BM-cMSCs not only preserved the structure of salivary glands but also transdifferentiated into functional salivary epithelial cells, suggesting a mechanism of action that supports tissue repair and restoration.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraglandular transplantation of bone marrow-derived clonal mesenchymal stem cells for amelioration of post-irradiation salivary gland damage. Lim, JY., Yi, T., Choi, JS., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10922976/

Functionality of Bone Marrow Mesenchymal Stromal Cells ... This study provides preliminary data supporting the feasibility of using autologous MSC(M) from HNC patients to treat RT-induced salivary dysfunction. Keywords: ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04489732

NCT04489732 | MSC in Patients With Xerostomia Post ... This is a single center pilot study designed to determine the safety and tolerability of autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in ...

3. onclive.com onclive.com/view/partner-perspectives-mesenchymal-stromal-cells-could-serve-as-preventive-therapy-for-chronic-radiation-induced-dry-mouth

Partner Perspectives: Mesenchymal Stromal Cells Could ... A phase 1 trial is examining the use of mesenchymal stromal cells for treatment of radiation-induced xerostomia in patients who have completed ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0167814024000148

Functionality of bone marrow mesenchymal stromal cells ... This study provides preliminary data supporting the feasibility of using autologous MSC(M) from HNC patients to treat RT-induced salivary dysfunction.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9365378/

Primary Results of the MESRIX Phase I/II Randomized Trial Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT02513238?term=PHENDIMETRAZINE&rank=5

Mesenchymal Stemcells for Radiation Induced Xerostomia The current study aims to assess the safety and feasibility of the injection of autologous adipost tissue derived MSCs on radiation-induced salivary gland ...