AzTrials
AzTrials

Xerostomia Following RadiotherapyPhase 1NCT04489732

MSC in Patients With Xerostomia Post XRT in Head and Neck Cancer

A Phase 1 study testing Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells in people with Xerostomia Following Radiotherapy, run by University of Wisconsin, Madison at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

This is a single center pilot study designed to determine the safety and tolerability of autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in patients with xerostomia (dry mouth) after undergoing radiation therapy (XRT) for head and neck cancer (HNC). Read more about this study

Who is it for?
Ages 18 to 90 years
Conditions the study is for
Xerostomia Following Radiotherapy
What is being tested?
Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
6 participants
Where
1 siteUnited States
Study dates
18 Feb 2022to 20 May 2026
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Willing to provide informed consent
  • Willing to comply with all study procedures and be available for the duration of the study
  • Histological diagnosis of Head and Neck Cancer (HNC) and ≥ 2 years from completion of treatment for HNC, either clinically or radiologically No Evidence of Disease (NED), as assessed by ENT or Radiation Oncologist within 28 days of study registration
  • Individuals at least 18 years of age and no older than 90 years of age
  • Xerostomia defined as less than or equal to 80 percent of baseline (pre-radiation) salivary function per patient estimate
  • Karnofsky performance status ≥ 70, patient eligible for bone marrow aspirate with wakeful anesthesia
Show all 12Show fewer
  • Radiographically confirmed bilateral submandibular glands
  • Females of childbearing potential must agree to have a negative urine or serum pregnancy test within 7 days prior to bone marrow biopsy. A female of child-bearing potential is any woman (regardless of sexual orientation, having undergone a tubal ligation, or remaining celibate by choice) who meets the following criteria:
  • has not undergone a hysterectomy or bilateral oophorectomy; or
  • has not been naturally postmenopausal for at least 12 consecutive months (i.e., has had menses at any time in the preceding 12 consecutive months)
  • Women of childbearing potential in sexual relationships with men must have used an acceptable method of contraception for 30 days prior to study registration and agree to use an acceptable method of contraception until 4 weeks after completing study treatment. Males must agree to avoid impregnation of women during and for four weeks after completing study treatment through use of an acceptable method of contraception.
  • Note: Acceptable method of contraception includes, but is not limited to, barrier with additional spermicidal foam or jelly, intrauterine device, hormonal contraception (started at least 30 days prior to study enrollment), intercourse with men who underwent vasectomy)

Who cannot join

  • History of sialolithiasis
  • Patients with one submandibular gland
  • History of autoimmune diseases affecting salivary glands, including Sjögren's syndrome, lupus, scleroderma, type I diabetes, sarcoidosis, and amyloidosis
  • Chronic graft vs host disease
  • Untreated oral candidiasis
  • Use of anti-cholinergic medications (e.g. atropine, ipratropium, oxybutynin, scopolamine, solifenacin, tiotropium, etc…) while enrolled on study
Show all 12Show fewer
  • Malignancy within the past 2 years, except adequately treated stage I lung cancer, low risk prostate cancer that has been treated or is undergoing active surveillance, adequately treated non-melanoma skin cancer, adequately treated ductal carcinoma in situ (DCIS), or adequately treated stage I cervical cancer
  • Expected life expectancy ≤ 6 months
  • Lidocaine allergy
  • Use of investigational drugs, biologics, or devices within 30 days prior to enrollment
  • Women who are pregnant, lactating or planning on becoming pregnant during the study
  • Not suitable for study participation due to other reasons at the discretion of the investigators

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Wisconsin

    Madison, Wisconsin, 53705

Other trials in United States

About this study

Official title: Pilot Study of Mesenchymal Stromal Cells in Patients With Xerostomia After Radiation Therapy for Head and Neck Cancer

This is a single center pilot study designed to determine the safety and tolerability of autologous bone marrow-derived Mesenchymal Stromal Cells (MSCs) in patients with xerostomia (dry mouth) after undergoing radiation therapy (XRT) for head and neck cancer (HNC). Up to 12 participants will be enrolled and can expect to be on study for up to 2 years.

Read the detailed description

Following the completion of screening/baseline procedures, and written consent, eligible participants will undergo bone marrow aspirate in order to obtain MSCs.

The MSC Investigational Medicinal Product (IMP) (dose level 0, n=6, staggered) will be injected into one submandibular gland under local anesthesia, in the gland that received the lowest radiation dose. Patients with only one submandibular gland will be ineligible.

All participants will be called by a study coordinator 3 days (+/- 2 days) after injection to assess pain and will have a phone visit with a physician 1 week (+/- 2 days) after injection during which the investigator will assess pain and ask about the area of injection regarding redness and/or swelling. All participants will complete a pain diary with daily entries over the first month to record the occurrence and severity of pain using a 0-10 visual analog scale and occurrence and severity of other adverse events (e.g., redness, swelling, warmth, tenderness, rash, pruritis, nausea, vomiting, fatigue). Participants will also keep a log of all pain medications taken including both narcotic and non-narcotic medications (e.g. ibuprofen, acetaminophen, etc.) for the first month. Participants will complete 5 follow-up visits over the course of 24 months - at 1, 3, 6, 12, and 24 months following the intervention. Salivary collection for analysis as well as QoL surveys will be obtained at these visits.

Dose Reduction:

  • If dose limiting toxicity (DLT) in less than or equal to 1 participant (n=6 participants, staggered at least 14 days), Dose Level 0 will be recommended as starting dose for subsequent trial.
  • If DLT in greater than 1 participant, dose level -1 will be administered, staggered at least 14 days in n=6 participants.
  • If DLT in this cohort is in less than or equal to 1 participant, Dose Level -1 will be recommended as starting dose for subsequent trial. If DLT in greater than or equal to 2 participants, study will be stopped.

Primary Objective

  • To evaluate the safety and tolerability of MSCs for subjects with xerostomia after radiation therapy for HNC.

Secondary Objectives

  • To evaluate the efficacy of MSCs for treatment of xerostomia and salivary hypofunction via quality-of-life (QoL) questionnaires, salivary amount, and salivary compositional analysis.
  • To assess the imaging characteristics in HNC patients after MSC injection using ultrasound.
  • To assess the feasibility of a future Phase 1 dose-escalation study.

Per Amendment Approved 4/14/23: Sub-study added, all enrolled participants will be offered injection of MSCs into the contralateral submandibular gland upon completion of the trial's primary objective (1 month of follow-up after injection of MSCs without any DLTs). The MSC IMP will be injected into the contralateral submandibular gland under local anesthesia.

Participants will complete 5 follow-up visits over the course of 24 months - at 1, 3, 6, 12, and 24 months following the contralateral injection. Salivary collection for analysis as well as QoL surveys will be obtained at all visits, except the 24 month follow-up visit.

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

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Single dose, starting at

    • Dose Level 0: 10 (8-12) x 10^6 injected into one submandibular gland on Day 1

    Sub-study for second injection after primary objectives met, 10 (8 - 12) x 10^6 MSCs will be offered for injection into each participant's contralateral submandibular gland

Study groups in NCT04489732
Study groupRoleWhat they receive
Treatment with MSCsExperimentalA 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.
Receives: Biological: Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Percentage of Subjects Experiencing Dose Limiting Toxicity (DLT)

    Dose limiting toxicity is defined as: submandibular pain > 5 on a pain scale of 0-10 at 1-month after MSC injection OR any serious AE OR any of the selected toxicities listed per protocol within one-month post-injection.

    Measured: up to 1 month post injection (up to 3 months from consent)

Secondary outcomes (11)

  1. Change in Saliva Production Rate

    Whole saliva production rates will be measured under unstimulated and stimulated saliva collection conditions.

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  2. Saliva Composition Analysis: Change in Salivary pH

    Salivary pH will be measured using a pH meter. The normal range of saliva pH is 6.2-7.6 .

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  3. Saliva Composition Analysis: Change in Total Protein Concentration in Saliva

    ELISA will be used to quantify total protein concentration in saliva. The normal range of total protein in saliva is 2-5 mg/mL.

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  4. Saliva Composition Analysis: Change in Amylase Concentration in Saliva

    The enzyme-linked immunosorbent assay (ELISA) will be used to quantify amylase concentration in saliva. The normal range of amylase concentration in saliva is 10-150 U/mL.

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  5. Saliva Composition Analysis: Change in Mucin Concentration in Saliva

    ELISA will be used to quantify mucin concentration in saliva.The normal range of mucin concentration in saliva is 1,000-3,000 ug/mL.

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  6. Change in The University of Michigan Xerostomia Related Quality of Life (XeQOL) Score

    The University of Michigan Xerostomia Related Quality of Life (XeQOL) scale is a validated patient-reported assessment 15 item scale with 4 domains: physical functioning, pain/discomfort, personal/psychologic functioning, and social functioning. Participants will answer the questions on a scale of 1-5 (not a all, a little, somewhat, quite a bit, very much) for every item. Higher scores represent greater degree of symptoms.

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  7. Change in The MD Anderson Dysphagia Index (MDADI) Score

    The MDADI is a 20-item questionnaire designed for evaluating the impact of dysphagia on the quality of life of patients with head and neck cancer. The MDADI score ranges from 20-100 with a lower scale representing worse dysphagia.

    Measured: baseline(up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  8. Change in Visual Analogue Scale (VAS) Xerostomia Score

    A Visual Analogue Scale questionnaire for subjective assessment of salivary dysfunction. The VAS xerostomia questionnaire is an 8-item questionnaire that provides a validated measure of the perception of dry mouth. Participants will be asked to mark their responses to each item by placing a vertical line on the 100-mm horizontal scale. The VAS ranges from 8-80 with a lower scale representing less dysphagia/symptoms

    Measured: baseline (up to 8 weeks before injection), 1, 3, 6, 12, and 24 months post-injection

  9. Change in Salivary Gland Size

    Salivary gland size measured by ultrasound imaging

    Measured: baseline (up to 8 weeks before injection), 3, 6, and 12 months post-injection

  10. Change in Salivary Gland Stiffness Measured by Shear Wave Velocity

    Salivary gland stiffness (fibrosis) will be measured by acoustic radiation force impulse imaging. Evaluators will be blinded to the time point of evaluation (pre- or post- MSC injection)

    Measured: baseline (up to 8 weeks before injection), 3, 6, and 12 months post-injection

  11. Participant Drop Out Rate

    Study feasibility will in part be measured by participant drop out rate.

    Measured: up to 24 months post-injection (up to 26 months from consent)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted28 Jul 2020
  2. Study start18 Feb 2022
  3. Primary completion22 Nov 2022
  4. Study completion20 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Model description
single-center, open-label, non-randomized, non-placebo controlled, single-group assignment, pilot study
Masking
None (open label)
Enrolment
6 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04489732
Sponsor's protocol ID
2020-1290
Other IDs
A533300, SMPH/HUMAN ONCOLOGY/HUMAN ONCO, UW20025, NCI-2021-00070, 1UG3DE030431-01, Protocol Version 9/28/2023, Head & Neck SPORE
Status last verified
Apr 2026
First submitted
23 Jul 2020
Last updated
20 Jul 2026
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Blitzer GC, Glazer T, Burr A, Gustafson S, Ganz O, Meyers R, McDowell KA, Nickel KP, Mattison RJ, Weiss M, Chappell R, Rogus-Pulia NM, Galipeau J, Kimple RJ. 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. Cytotherapy. 2023 Nov;25(11):1139-1144. doi: 10.1016/j.jcyt.2023.07.009. Epub 2023 Aug 15.

    PubMed 37589639

  • Blitzer GC, Rogus-Pulia NM, Mattison RJ, Varghese T, Ganz O, Chappell R, Galipeau J, McDowell KA, Meyers RO, Glazer TA, Kimple RJ. 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. Cytotherapy. 2022 May;24(5):534-543. doi: 10.1016/j.jcyt.2021.11.003. Epub 2022 Feb 16.

    PubMed 35183442

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Autologous bone-marrow derived, interferon gamma stimulated mesenchymal stromal cells in people with Xerostomia Following Radiotherapy, run by University of Wisconsin, Madison at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Feb 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Percentage of Subjects Experiencing Dose Limiting Toxicity (DLT) (time frame: up to 1 month post injection (up to 3 months from consent)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04489732, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jul 2026.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in