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

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.

Study Overview

• Status: Completed
• Conditions: Head and Neck Cancer; Xerostomia
• Intervention / Treatment: Procedure: Bone Marrow Aspiration; Diagnostic test: Ultrasound Imaging of Salivary Glands; Other: Salivary Assay; Other: Quality of Life Instruments

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin Carbone Cancer Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 89 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Participants with Xerostomia; Salivary sample collection, quality of life survey, salivary gland imaging, bone marrow aspiration

Procedure: Bone Marrow Aspiration; collection of approximately 40 mL of bone marrow aspirate; Other Names: Bone Marrow Collection; Diagnostic test: Ultrasound Imaging of Salivary Glands; Salivary gland size will be measured by ultrasound.; Other: Salivary Assay; Whole saliva production rates (sialometry) will be measured under unstimulated (first passive drool method) and stimulated (chewing gum) saliva collection conditions; Other Names: sialometry; Other: Quality of Life Instruments; 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.

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare Secretome Profile of MSCs Between Participant Groups: ELISA	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).	up to 6 months
Compare Secretome Profile of MSCs Between Participant Groups: Western Blot	The secretome profile of MSCs from HNC participants treated with radiation, chemoradiation, or previously untreated will be statistically compared using and western blots.	up to 6 months

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Investigators: Principal Investigator: Randall Kimple, PhD, University of Wisconsin, Madison

Publications and helpful links

Helpful Links

• University of Wisconsin Carbone Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): October 18, 2019
• Primary Completion (Actual): March 10, 2021
• Study Completion (Actual): March 10, 2021

Study Registration Dates

• First Submitted: June 26, 2019
• First Submitted That Met QC Criteria: July 1, 2019
• First Posted (Actual): July 5, 2019

Study Record Updates

• Last Update Posted (Actual): March 24, 2021
• Last Update Submitted That Met QC Criteria: March 23, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: radiation; head and neck cancer; mesenchymal stem cells; adult stem cells; MSC; HNC; Dry Mouth; salivary gland
• Additional Relevant MeSH Terms: Neoplasms; Neoplasms by Site; Stomatognathic Diseases; Mouth Diseases; Salivary Gland Diseases; Head and Neck Neoplasms; Xerostomia
• Other Study ID Numbers: UW19009; A533300 (Other Identifier: UW Madison); SMPH/HUMAN ONCOLOGY/HUMAN ONCO (Other Identifier: UW Madison); 2019-0497 (Other Identifier: Institutional Review Board); Protocol Version 7/24/2020 (Other Identifier: UW Madison)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No