Neoplasms

All Conditions

Mouth and Tooth Diseases

Head and Neck Neoplasms

Xerostomia

Salivary Gland Diseases

Mouth Diseases

Stomatognathic Diseases

Injection of MSCs into submandibular glands at pre-specified dose level:

* Dose -1: 5 (4 - 6) x10\^6 MSCs (to be used only if Dose level 1 is not tolerated) per gland (0.5 ml)
* Dose 0: 10 (8 - 12) x10\^6 MSCs per gland (1 ml)
* Dose 1: 20 (16 - 24) x10\^6 MSCs per gland (2 ml)

Cancer Connect

Randall Kimple, MD, PhD

Jacques Galipeau, MD

The goal of this clinical research study is to evaluate the safety and tolerability of injecting certain cells that you produce in your bone marrow called mesenchymal stem cells (MSCs) into your salivary glands.

Participants will have head and neck cancer that was treated with radiation therapy, and in this study will:

* Undergo a collection of bone marrow using a needle;
* Donate saliva;
* Undergo a salivary gland ultrasound; and,
* Complete questionnaires that ask about dry mouth

Participants can expect to be in this study for up to 30 months.

Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy

A Phase I Dose-Escalation Trial of Mesenchymal Stromal Cells in Patients With Xerostomia After Radiation Therapy for Head and Neck Cancer

RP2D (also called the maximum tolerated dose) of MSCs determined by the proportion of subjects experiencing dose limiting toxicity (DLT)

Incidence of pain assessed as greater than 5 on standard 0-10 point pain scale (0=not at all to 10=worst pain imaginable)

Incidence of pre-specified adverse events

Efficacy of MSC assessed through University of Michigan Xerostomia Related Quality of Life (XeQOL) scale, which is a 15-item assessment scale with 4 domains. The score is the average of all responses of all domains and can range from 0 to 4, where higher scores indicate increased xerostomia burden.

Efficacy of MSC assessed through the MD Anderson Dysphagia Index (MDADI), which is a 20-item questionnaire designed for evaluating the impact of dysphagia (swallowing ability). Scores range from 20 (extremely low functioning) to 100 (high functioning).

Efficacy of MSC assessed through VAS xerostomia questionnaire, which is an 8-item questionnaire that measures the perception of dry mouth. Scores range from 0-10, with 0 being low dryness and 10 being high dryness.

Saliva production will be measured by having participants chew inert gum base to the pace of a metronome (70 beats per minute) while expectorating saliva (without swallowing) into the saliva collection aid for 5 minutes total40. Cryovials will be weighed before and after collection and the difference in weight (g) will represent the amount of saliva produced in 5 minutes for each condition.

Assess imaging characteristics of submandibular glands after MSC, measured by ultrasound

National Institute of Dental and Craniofacial Research (NIDCR)

University of Wisconsin, Madison

Salivary sample collection, quality of life survey, salivary gland imaging, bone marrow aspiration

collection of approximately 40 mL of bone marrow aspirate

Bone Marrow Aspiration

Salivary gland size will be measured by ultrasound.

Ultrasound Imaging of Salivary Glands

Whole saliva production rates (sialometry) will be measured under unstimulated (first passive drool method) and stimulated (chewing gum) saliva collection conditions

Salivary Assay

Participants will self-assess with the following Quality of Life (QoL) surveys: University of Michigan Xerostomia related quality of life scale (XeQOL), the MD Anderson Dysphagia Index (MDADI), and the VAS xerostomia questionnaire.

Quality of Life Instruments

Randall Kimple, PhD

Xerostomia, or dry mouth, is a common side effect of head neck radiation. Current treatment options for radiation-induced xerostomia are generally supportive in nature. Most of these supportive interventions do not reverse xerostomia and are palliative in intent.

The investigators propose that autotransplantation of marrow-derived mesenchymal stromal cells (MSCs) in salivary glands post-RT or post-chemoradiation therapy (CRT) may provide an innovative remedy to treat xerostomia and restore quality of life.

Participants can expect to be on study for up to 6 months.

This feasibility study will analyze the salivary composition, salivary viscoelasticity, salivary gland US, and QoL surveys of participants without head and neck cancer (HNC) to determine standard values. The investigators will then compare this to the salivary composition and viscoelasticity of participants with treated HNC.

Additionally, the investigators will examine the paracrine factors of marrow MSCs in order to prove a hypothesis that paracine factors constitutively expressed by marrow MSCs \[Wnts, fibroblast growth factors (FGFs), GDNF and others\] will directly influence the biology of dormant salivary gland stem cells following intraglandular transplantation and allow for functional recovery following RT.

Primary Objective

* To determine the feasibility of in vitro expansion of marrow-derived MSCs from HNC patients to \>50 million cells.

Secondary Objectives

* To assess the stability of salivary function in HNC patients using quality-of-life (QoL) questionnaires and salivary composition analysis.
* To assess the stability of salivary gland size as measured by ultrasound.

Correlative Objectives

* To compare assess the secretome profile of MSCs from HNC patients treated with radiation or, chemoradiation, or previously untreated.
* To compare the salivary composition, viscoelasticity, salivary gland ultrasound, and QoL of HNC patients to non-HNC patients

Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia

Salivary Gland Autotransplantation of Marrow Mesenchymal Stromal Cells for Treatment of Radiation-induced Xerostomia - FDA IND (Investigational New Drug) Enabling Studies

The secretome profile of MSCs from HNC participants treated with radiation, chemoradiation, or previously untreated will be statistically compared using enzyme-linked immunosorbent assay (ELISA).

The secretome profile of MSCs from HNC participants treated with radiation, chemoradiation, or previously untreated will be statistically compared using and western blots.

The feasibility of in vitro expansion of MSCs derived from marrow aspirates collected from participants will be determined by if they can be culture expanded for up to two weeks to generate \>50 million MSCs per donor. Feasibility will reported as the number of participants whose marrow-derived MSCs can be expanded in vitro to \> 50 million cells within two weeks.

The University of Michigan Xerostomia related quality of life scale (XeQOL) is a 15-item questionnaire about how a participants oral health affects their life. Each item is scored from 1-5 either 'not at all', 'a little', 'somewhat', 'quite a bit', or 'very much' for a total score of 15-75. Higher scores represent greater degree of symptoms.

The MD Anderson Dysphagia Inventory (MDADI) is a 20-item questionnaire about how a participants perceive their swallowing ability. Each item is scored from 'strongly agree', 'agree', 'no opinion', 'disagree', or 'strongly disagree'. One question provides a 'global score between 1-5 where 1 is extremely low functioning and 5 is high functioning. The remaining 19 questions measure a composite score from 20-100 where higher scores represent higher degree of function.

The Visual Analogue Scale (VAS) - xerostomia questionnaire is an 8-item questionnaire about how a participant perceives their dry mouth. Each item is visually scored on a sliding scale (100mm in length) between two extremes (Q1 and Q2 from 'not difficult at all' to 'very difficult', Q3 from 'A lot' to 'None', Q4-Q7 from 'Not Dry at All' to 'Very Dry', and Q8 from 'Not Thirsty at All' to 'Very Thirsty'. The participant places a line on the scale to mark their answer. Change between various time points can be determined based on measured distance along the scale for each answer.

Unstimulated saliva production will be measured at two time points by the passive drool method over a 5-minute time frame. Participants will allow saliva to pool in the mouth and, then, with head tilted forward, gently guide saliva into a saliva collection aid attached to a cryovial. Difference in weight of the cryovial empty and after the test will represent the amount of saliva produced.

Stimulated saliva production will be measured at two time points by having participants chew inert gum base to the pace of a metronome (70 beats per minute) while expectorating saliva (without swallowing) into the saliva collection aid for 5 minutes total. Difference in weight of the cryovial empty and after the test will represent the amount of saliva produced.

The size of salivary glands will be measured via ultrasound at baseline and up to 6 months on study.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study Transplanting Bone Marrow Cells Into Salivary Glands to Treat Dry Mouth Caused by Radiation Therapy	NCT05820711	Head and Neck C... Xerostomia	MSC	18 Years - 90 Years	University of Wisconsin, Madison
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison
Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia	NCT04007081	Xerostomia Head and Neck C...	Bone Marrow Asp... Ultrasound Imag... Salivary Assay Quality of Life...	18 Years - 89 Years	University of Wisconsin, Madison

Spots Global Cancer Trial Database for msc

Every month we try and update this database with for msc cancer trials from around the world to help patients and their families find trials that might be right for them.
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Spots Global Cancer Trial Database for msc

Every month we try and update this database with for msc cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for msc cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.