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

This study has been withdrawn prior to enrollment.
Sponsor:
Information provided by (Responsible Party):
Loma Linda University
ClinicalTrials.gov Identifier:
NCT01532479
First received: February 8, 2012
Last updated: October 13, 2014
Last verified: October 2014
  Purpose

The purpose of this study is to determine if Hyperbaric Oxygen (HBO) therapy improves salivary gland function in previously head-and-neck irradiated patients. The following will be evaluated: salivary a-amylase, IGF-1, Thrombospondin-1, and VEGF-A concentrations, resting and stimulated salivary flow rate and pH, and salivary buffering capacity. Demographic data, past medical/surgical histories, social history and habits, risk factors, medication list, nutritional status, stage and location of tumor treated, dose/duration of radiation, and time elapsed since radiation treatment will be reviewed and recorded. Subjects will complete a quality of life questionnaire, describe (presence/absence) dry mouth symptoms prior to HBO therapy, and provide current A1c level, or submit to a finger stick. The following groups will be evaluated: 1. Head-and-neck irradiated subjects with ORN (indicating HBO therapy) 2. Subjects with other conditions indicating HBO therapy (positive control), and 3. Head-and-neck irradiated subjects without ORN (negative control). Subjects will include 78 males or females, 18 years old and over. In total, participation will last 22 weeks.


Condition
Osteoradionecrosis of the Jaw
Xerostomia

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: Saliva, Hyperbaric Oxygen Therapy, & Gland Function: A Prospective Study

Resource links provided by NLM:


Further study details as provided by Loma Linda University:

Primary Outcome Measures:
  • Volume of Stimulated Saliva [ Time Frame: Pre-treatment to post treatment, average duration of 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Concentrations of Salivary Thrombospondin-1 [ Time Frame: Measured weekly, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]
    Measurements will occur at baseline and weekly throughout treatment with one post treatment measurement one week after last treatment

  • Concentration of Salivary IGF-1 [ Time Frame: Measured weekly, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]
    Measurements will occur at baseline and weekly throughout treatment with one post treatment measurement one week after last treatment

  • Concentration of Salivary VEGF-A [ Time Frame: Measured weekly, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]
    Measurements will occur at baseline and weekly throughout treatment with one post treatment measurement one week after last treatment

  • Salivary pH [ Time Frame: Measured weekly, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]
    Measurements will occur at baseline and weekly throughout treatment with one post treatment measurement one week after last treatment

  • Salivary buffering capacity [ Time Frame: Measured weekly, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]
    Measurements will occur at baseline and weekly throughout treatment with one post treatment measurement one week after last treatment

  • Impact of HBO treatment on quality of life for ORN patients with xerostomia [ Time Frame: Pre to Post Treatment, average duration of treatment is 12 weeks ] [ Designated as safety issue: No ]

Enrollment: 0
Study Start Date: August 2015
Estimated Study Completion Date: January 2022
Estimated Primary Completion Date: August 2021 (Final data collection date for primary outcome measure)
Groups/Cohorts
Treatment Group
Subjects with ORN treated with Hyperbaric Oxygen Therapy
Postive Control Group
Subjects treated with Hyperbaric Oxygen Therapy that have not had head or neck radiation therapy
Negative Control Group
Subjects who have had head and neck radiation that have not had Hyperbaric Oxygen Therapy

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

Patients in the Loma Linda University Healthcare System

Criteria

Inclusion Criteria:

  • Patient age: 18+.
  • Patient must give informed consent.

Treatment Group

  • Patient has completed head and neck irradiation treatment.
  • Hyperbaric oxygen therapy is indicated and patient has accepted said treatment.
  • Patient must be able to complete hyperbaric oxygen course of treatment.

Positive Control Group

  • Hyperbaric oxygen therapy is indicated and patient has accepted said treatment.
  • Patient must be able to complete hyperbaric oxygen course of treatment.

Negative Control Group

  • Patient has completed head and neck irradiation treatment.
  • Hyperbaric oxygen therapy has not been used.

Exclusion Criteria:

  • Currently using anti-cholinergic agent, eg: Scopolamine patch, Atropine, Ipratropium, Spiriva.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01532479

Locations
United States, California
Loma Linda University Health System
Loma Linda, California, United States, 92354
Sponsors and Collaborators
Loma Linda University
Investigators
Principal Investigator: Takkin Lo, MD, MPH Loma Linda University School of Medicine
  More Information

No publications provided

Responsible Party: Loma Linda University
ClinicalTrials.gov Identifier: NCT01532479     History of Changes
Other Study ID Numbers: SHTGN-001
Study First Received: February 8, 2012
Last Updated: October 13, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Loma Linda University:
Osteoradionecrosis
Xerostomia

Additional relevant MeSH terms:
Osteoradionecrosis
Xerostomia
Mouth Diseases
Radiation Injuries
Salivary Gland Diseases
Stomatognathic Diseases
Wounds and Injuries

ClinicalTrials.gov processed this record on October 23, 2014