Clinical trial NCT04007081: Salivary Gland Autotransplantation for Treatment of XRT Induced Xerostomia
Official title: Salivary Gland Autotransplantation of Marrow Mesenchymal Stromal Cells for Treatment of Radiation-induced Xerostomia - FDA IND (Investigational New Drug) Enabling Studies
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Xerostomia
Head and Neck Cancer
Keywords: Dry Mouth
MSC
mesenchymal stem cells
adult stem cells
head and neck cancer
salivary gland
radiation
HNC
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
First posted: 2019-07-05
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 89
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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

Eligibility criteria: 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)

Primary outcomes:
measure: Number of Participant's whose Marrow-Derived MSCs Can be Expanded in vitro to > 50 million cells within two weeks
timeFrame: Up to 1 day to collect, subsequently cultured in vitro for up to 2 weeks
Secondary outcomes:
measure: Change in participant QoL: XeQOL
timeFrame: baseline and up to 6 months
measure: Change in participant QoL: MDADI
timeFrame: baseline and up to 6 months
measure: Change in participant QoL: VAS
timeFrame: baseline and up to 6 months
measure: Change in participant Salivary Function: Unstimulated
timeFrame: baseline and up to 6 months
measure: Change in participant Salivary Function: Stimulated
timeFrame: baseline and up to 6 months
measure: Change in participant Salivary Gland Size
timeFrame: baseline and up to 6 months
Other outcomes:
measure: Compare Secretome Profile of MSCs Between Participant Groups: ELISA
timeFrame: up to 6 months
measure: Compare Secretome Profile of MSCs Between Participant Groups: Western Blot
timeFrame: up to 6 months
Locations:
city: Madison
country: United States
facility: University of Wisconsin Carbone Cancer Center
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Randall Kimple, PhD
role: PRINCIPAL_INVESTIGATOR
References: