Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia

Study Overview
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Brief Summary
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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.

Detailed Description
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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

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

Conditions
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Xerostomia, Head and Neck Cancer

Intervention / Treatment
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* Procedure: Bone Marrow Aspiration
* Diagnostic Test: Ultrasound Imaging of Salivary Glands
* Other: Salivary Assay
* Other: Quality of Life Instruments


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants ≥2 years from completion of chemoradiation therapy or radiation therapy (N=6) with subjective complaint of xerostomia or with no diagnosis of HNC (N=5) Karnofsky ≥ 60, participant eligible for bone marrow aspirate with wakeful anesthesia Not pregnant Willing and able to give informed consent non-HNC participants only need to meet the following applicable inclusion criteria No history of radiation to the salivary glands Willing and able to give informed consent Exclusion Criteria: Salivary gland disease (e.g., sialolithiasis)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 89 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Participants with Xerostomia<br>Salivary sample collection, quality of life survey, salivary gland imaging, bone marrow aspiration | Procedure: Bone Marrow Aspiration<br>* collection of approximately 40 mL of bone marrow aspirate<br>* Other names: Bone Marrow Collection;Diagnostic Test: Ultrasound Imaging of Salivary Glands<br>* Salivary gland size will be measured by ultrasound.<br>Other: Salivary Assay<br>* Whole saliva production rates (sialometry) will be measured under unstimulated (first passive drool method) and stimulated (chewing gum) saliva collection conditions<br>* Other names: sialometry;Other: Quality of Life Instruments<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participant's whose Marrow-Derived MSCs Can be Expanded in vitro to > 50 million cells within two weeks | 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. | Up to 1 day to collect, subsequently cultured in vitro for up to 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in participant QoL: XeQOL | 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. | baseline and up to 6 months | 
| Change in participant QoL: MDADI | 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. | baseline and up to 6 months | 
| Change in participant QoL: VAS | 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. | baseline and up to 6 months | 
| Change in participant Salivary Function: Unstimulated | 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. | baseline and up to 6 months | 
| Change in participant Salivary Function: Stimulated | 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. | baseline and up to 6 months | 
| Change in participant Salivary Gland Size | The size of salivary glands will be measured via ultrasound at baseline and up to 6 months on study. | baseline and up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dry Mouth, MSC, mesenchymal stem cells, adult stem cells, head and neck cancer, salivary gland, radiation, HNC