Stem Cell Therapy for Dry Mouth After Cancer Treatment

Overseen By Cancer Connect

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: University of Wisconsin, Madison

Must not be taking: Anti-cholinergics

Disqualifiers: Autoimmune diseases, Malignancy, others

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

Compensation: Varies

Number of Visits: 11

Duration: 1 month

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new stem cell therapy for individuals experiencing dry mouth after radiation treatment for head and neck cancer. Researchers aim to determine if injecting these special cells, taken from the patient's own bone marrow, is safe and can enhance saliva production. The trial targets those who completed cancer treatment at least two years ago and continue to suffer from dry mouth affecting daily life. As a Phase 1 trial, participants will be among the first to receive this innovative treatment, aiding researchers in understanding its effects in people.

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

The trial requires that you stop using anti-cholinergic medications (drugs that reduce saliva production) while enrolled. Other medications are not specifically mentioned, so it's best to discuss your current medications with the study team.

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

Research has shown that using a person's own bone marrow cells is safe for treating dry mouth after cancer treatment. In earlier studies, researchers injected these cells into one of the salivary glands. Most participants did not experience serious side effects, suggesting the treatment is safe so far. However, as this is a Phase 1 trial, the primary goal is to test safety and tolerability, so further research is needed to confirm these findings. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for dry mouth after cancer therapy, which often include saliva substitutes and medications to stimulate saliva production, this new approach uses autologous bone-marrow derived mesenchymal stromal cells (MSCs). These cells are stimulated with interferon gamma to enhance their regenerative capabilities. Researchers are excited because MSCs are injected directly into the submandibular glands, aiming to repair and regenerate damaged tissue, potentially offering a more long-lasting solution. This innovative approach directly targets the cause of dry mouth by addressing gland damage rather than just alleviating symptoms.

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

Research has shown that certain cells, called mesenchymal stromal cells (MSCs), might help treat dry mouth after cancer treatment. In a previous study, patients who received these cells produced more saliva. In this trial, participants will receive MSCs, taken from their own bone marrow and treated with a protein called interferon gamma to enhance healing effects. Early results suggest that these cells can help restore saliva in people with dry mouth caused by radiation therapy for head and neck cancer. This method offers a promising option for those dealing with this uncomfortable condition. ^{1 3 4 6 7}

Who Is on the Research Team?

Randall J 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 a history of head and neck cancer who are now disease-free for at least 2 years post-treatment. Participants must have significant dry mouth after radiation therapy, be able to give consent, undergo bone marrow biopsy under local anesthesia, and not be pregnant or planning pregnancy. Contraception use is required.

Inclusion Criteria

I believe my saliva production is less than 80% of what it was before radiation.

I have confirmed I am not pregnant and will use birth control during and after the study.

Willing to provide informed consent

Exclusion Criteria

I haven't had cancer in the past 2 years, except for certain low-risk or treated early-stage cancers.

The researchers have decided that you are not suitable to participate in the study for other reasons.

I have an autoimmune disease like Sjögren's, lupus, or type I diabetes.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a single dose of MSCs injected into the submandibular gland under local anesthesia

1 month

1 visit (in-person), 1 phone call, 1 phone visit

Follow-up

Participants are monitored for safety and effectiveness after treatment, with salivary collection and QoL surveys

24 months

5 visits (in-person) at 1, 3, 6, 12, and 24 months

Sub-study Extension

Participants are offered injection of MSCs into the contralateral submandibular gland upon completion of the trial's primary objective

24 months

5 visits (in-person) at 1, 3, 6, 12, and 24 months following contralateral injection

What Are the Treatments Tested in This Trial?

Interventions

• Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells

Trial Overview The study tests the safety of using one's own modified bone marrow cells (MSCs) to treat severe dry mouth caused by radiation in head and neck cancer treatment. Up to 12 patients will receive this experimental therapy and will be monitored for up to two years.

How Is the Trial Designed?

Group I: Treatment with MSCs Experimental Treatment 1 Intervention

A single dose of MSCs injected into the submandibular glands of patients with radiation-induced xerostomia (primary objective) Following primary outcomes, a second injection of 10 (8 - 12) x 106 MSCs will be offered for injection into each participant's contralateral submandibular gland.

Who Is Running the Clinical Trial?

University of Wisconsin, Madison

Lead Sponsor

Trials

1,249

Recruited

3,255,000+

University of Wisconsin Carbone Cancer Center (UWCCC)

Collaborator

Trials

3

Recruited

20+

National Institute of Dental and Craniofacial Research (NIDCR)

Collaborator

Trials

312

Recruited

853,000+

Published Research Related to This Trial

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]

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]

Stem cell therapy shows promise as a treatment for severe dry mouth caused by salivary gland hypofunction, particularly in cases where traditional treatments like sialagogues are ineffective.

Research indicates that specific stem cells, such as CD133-positive cells from mouse submandibular glands, can regenerate damaged salivary glands, highlighting the potential of using tissue stem cells and embryonic stem cells in regenerative medicine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Application of regenerative medicine to salivary gland hypofunction. Tanaka, J., Mishima, K.[2021]

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]

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]

In a study involving 8 head and neck cancer patients with radiation-induced dry mouth, treatment with adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) significantly altered the salivary proteome, with 99 proteins showing differential expression after 120 days.

While AT-MSC treatment increased proteins associated with tissue regeneration, it did not fully restore the salivary profile to that of healthy controls, indicating that while the treatment has potential, it may not completely reverse the effects of radiation-induced damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraglandular mesenchymal stem cell treatment induces changes in the salivary proteome of irradiated patients. Lynggaard, CD., Jersie-Christensen, R., Juhl, M., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37589639/

A pilot, first-in-human study of interferon gamma-stimulated ... We performed a first-in-human pilot study of interferon gamma (IFNγ)-stimulated autologous bone marrow-derived MSCs, or MSC(M), for the treatment of radiation- ...

2. sciencedirect.com sciencedirect.com/science/article/pii/S1465324925001999

AUTOLOGOUS, BONE MARROW-DERIVED, IFNγ ... The Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients with Xerostomia After Radiation Therapy for Head and Neck Cancer

3. 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 ...

4. 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 ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10615723/

A pilot, first-in-human study of interferon gamma-stimulated ... Preliminary data suggests that mesenchymal stromal/stem cells (MSCs) can improve salivary function. We performed a first-in-human pilot study of interferon ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04489732?term=dry%20mouth&aggFilters=funderType:nih&viewType=Table&rank=8&tab=results

MSC in Patients With Xerostomia Post XRT in Head and ... Xerostomia Following Radiotherapy. Intervention/Treatment. Biological : Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells.

7. isct-cytotherapy.org isct-cytotherapy.org/article/S1465-3249(23)01010-1/fulltext

Marrow-Derived Autologous Stromal Cells for the ... Xerostomia, or the feeling of dry mouth, is a significant side effect of radiation therapy for patients with head and neck cancer (HNC).