Trial Information

Saliva, Hyperbaric Oxygen Therapy, & Gland Function: A Prospective Study

This is a prospective study in a human model examining treatment of patients who have
sustained damage to salivary glands following head and neck radiation, subsequent
xerostomia, and who are currently indicated for hyperbaric oxygen therapy for treatment of
osteoradionecrosis. Salivary flow rates, pH and buffering capacity before and after
hyperbaric oxygen treatments will be collected using GC America (Alsip, Illinois)
Saliva-Check BUFFER Kit and results will be recorded. The 6 tests take 10 minutes to
complete per patient. According to GC America, these tests are simple, demonstrate salivary
dysfunction, help identify factors affecting salivary dysfunction, and assist in the
diagnosis of xerostomia. Salivary testing and data collection will occur on 8 independent
visits over the course of hyperbaric oxygen treatment and during follow-up. Stimulated
saliva samples will be used to measure proteins that are involved in salivary gland
revascularization and repair. Saliva samples will be stored at less than or equal to -20C
for up to 1 year. Measurements of salivary VEGF-A, IGF-1, and Thrombospondin-1 will be
quantified using R&D Systems (Minneapolis, MN) ELISA kits and results will be recorded.
Salivary Alpha-Amylase will be measured using Rocky Mountain Diagnostics, Inc (Colorado
Springs, CO) Alpha-Amylase Saliva kit. Protein analysis will be done on stimulated saliva
samples collected at 4 independent visits: first week, fourth week, eighth week, sixteenth
week.

The medical, surgical, and health histories of each participant will be reviewed. Each
participant will complete the EORTC quality of life core questionnaire (QLQ - C30 v3.0),
including head and neck cancer module, at the start and completion of the trial. A blood
sample from each participant will be drawn, and analyzed for A1c levels and albumin levels.
During the first, fourth, eighth, and sixteenth week, following Saliva-Check BUFFER Kit
testing done before HBO therapy, additional saliva will be collected to ensure that a
minimum of 2 mL of saliva can be stored at less than or equal to -20 oC for protein
analysis.

After salivary testing, each patient will enter a hyperbaric oxygen chamber located at Loma
Linda University Medical Center. The patient will gradually be elevated to therapeutic
oxygen levels over an 8-12 minute period. At this time, 100% oxygen will be administered at
2.0 ATA or 2.5 ATA, at the discretion of the treating physician, for 90 minutes. A 10-minute
air-break will be given after the first 45 minutes if the patients are on the 2.5 ATA
protocol. At the conclusion of the oxygen treatment, the oxygen and pressure levels are
gradually decreased over 8-12 minutes to return to a depth of 1 ATA. After exiting the
hyperbaric oxygen chamber, salivary testing will once again be performed on each patient.

Collected data will be compared to two independent control groups. The Positive Control
Group will include 26 individuals who fit the inclusion and exclusion criteria: participants
for whom hyperbaric oxygen treatment is indicated, but who have not had radiation therapy
for head or neck cancer. The Negative Control Group will include the first 26 individuals
who fit the inclusion and exclusion criteria: participants who have previously had head and
neck radiation therapy, but for whom hyperbaric oxygen treatment is not indicated. Salivary
data for the Positive Control Group will be collected in such as way as to parallel data
collected for the Treatment Group. Salivary data will be collected in the same way for the
Negative Control Group with the following modifications: salivary flow rate testing will
only be performed once during each visit and salivary testing will be spaced on the basis of
time in days in contrast to number of hyperbaric oxygen treatment sessions.