Clinical Trial Details
— Status: Active, not recruiting
Administrative data
| NCT number |
NCT02294838 |
| Other study ID # |
BCCA H14-02236 |
| Secondary ID |
|
| Status |
Active, not recruiting |
| Phase |
N/A
|
| First received |
November 12, 2014 |
| Last updated |
November 25, 2016 |
| Start date |
December 2014 |
| Est. completion date |
February 2017 |
Study information
| Verified date |
November 2016 |
| Source |
British Columbia Cancer Agency |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Canada: Institutional Review Board |
| Study type |
Interventional
|
Clinical Trial Summary
The aim of this study is to determine the feasibility of demonstrating the following
physiologically-descriptive quantities ('metrics'): the volume of plasma/volume of tissue
(νp), Apparent Diffusion Coefficient (ADC), the volume of extracellular extravascular space
per volume of tissue (νe), and the contrast agent transfer coefficients (Ktrans) pre and
post parotid stimulation in 10 healthy volunteers. Feasibility will be defined as 80% of
volunteers achieving detectable signal changes in pre/post salivary MR images.
Description:
OBJECTIVES
Primary Objective:
Feasibility will be defined as 80% of volunteers achieving detectable signal changes in
pre/post salivary MR images (in either the IVIM or the DCE scans).
BACKGROUND INFORMATION AND RATIONALE
It is well known that loss of salivary function in the parotid glands leads to an elevated
risk of chronically dry-mouth. Xerostomia is thought to result from salivary function loss
due to damage of the functional aspects of the (saliva-producing) parotid gland, but the
precise nature is unknown. Recent reports have found regional dose susceptibility in rat
parotid(1); delivering dose to one region of the parotid results in a different incidence of
xerostomia than would that same dose to another region. Similarly, regional dose
susceptibility of subjective xerostomia (i.e. patient-reported) has been noted in human
parotid(2). It is presently unclear to what extent these findings relate to objective
functional loss, recovery, or xerostomia in humans. With this motivation, the investigators
launched a preliminary project to search for changes of parotid salivary function resulting
from irradiation during treatment for head-and-neck cancers. The Investigators hypothesis
was that certain regions of the parotid are more susceptible to radiation damage than
others.
To test this hypothesis, data collected prospectively from one-hundred patients who
underwent head-and-neck cancer treatment was analyzed for correlation between regional dose
and salivary function response. Three-dimensional dose distributions were harvested from
patient dose data and organ contours sub- segmented into a variety of regional "pieces".
Sub-segmentation was guided by clinical recommendation. Saliva output collected by clinical
staff was compared before and after treatment to provide a quantitative means of
establishing salivary response. The investigators were able to demonstrate salivary function
loss and recovery, but were unable to demonstrate regional susceptibility.
It was found that simple (scalar) saliva measurements and anatomical information alone do
not provide enough information for the functional biology that the investigators are trying
to describe. To investigate methods of obtaining functional data, the investigators have
engaged with Dr Stefan Reinsberg - a researcher in the Department of Physics and Astronomy
at the UBC. He develops methods for clinical and preclinical MRI for the diagnosis, planning
and treatment monitoring of cancer. Techniques of particular interest to him are dynamic
contrast-enhanced MRI and diffusion-weighted imaging. Through advanced statistical means he
attempts to maximize the information obtained about the functional status of tissue under
investigation.
As the precise site of radiation damage is thought to be the functional components (i.e.,
parenchyma) of the parotid, it is our belief that the use of patient-specific three
dimensional anatomical and functional information is the key to understanding. Therefore,
our previous data collection will be used to augment a non-invasive technique, known as
Dynamic Contrast-Enhanced Magnetic Resonance Imaging (DCE-MRI), which will allow us to
precisely quantify regional gland function while also providing a clearer view of the
glandular anatomy.
This data will be collected to optimize the technique and as preliminary (proof of concept)
for an intended future protocol that will be performed on head-and-neck Intensity-Modulated
Radiotherapy Treatment patients at three instances: prior to radiotherapy, and both three
months and one year after conclusion of the treatment.
TRIAL DESIGN Sample size 10, proof of concept feasibility trial where preliminary data can
be utilized for future study in patients undergoing active radiotherapy.
ELIGIBILITY CRITERIA There will be NO EXCEPTIONS to eligibility requirements at the time of
registration. Questions about eligibility criteria should be addressed PRIOR to
registration.
The eligibility criteria for this study have been carefully considered. Eligibility criteria
are standards used to ensure that patients who enter this study are medically appropriate
candidates for this therapy. For the safety of the participants, as well as to ensure that
the results of this study can be useful for making treatment decisions regarding other
patients with similar diseases, it is important that no exceptions be made to these criteria
for admission to the study.
Participants must fulfill all of the following criteria to be eligible for admission to the
study:
Age ≥ 18 Healthy normal volunteer
INELIGIBILITY CRITERIA
Subjects who fulfill any of the following criteria are not eligible for admission to the
study:
Pregnant women Scheduled to take unusual or uncommon chemotherapy agents or medication
Previous or about to undertake a course of radiotherapy Previous surgery to neck such as a
lymph node dissection. Must not have, or be willing to replace, metal fillings or other
foreign objects which will seriously impede image collection or analysis.
No contraindication to an MRI
PRE- MRI EVALUATION
Biochemistry Creatinine (GFR) <100 Dental assessment Check MRI check list to ensure
suitability
REGISTRATION PROCEDURES
ENTRY PROCEDURES A reason for ineligibility will be recorded for all participants that are
screened for the study but found to be ineligible. A record will be kept of all eligible
participants that decline participation.
TRIAL PROCEDURES
MRI scans will take place at the University of British Columbia Vancouver. Tissue relaxation
constant (T1) and magnetization value (M0) maps will be derived from 3 spoiled gradient echo
(GE) images acquired with flip angles α = 2◦, 10◦, and 30◦, 1×1×2 mm spatial resolution, and
image technique/contrast parameters TR = 2.8 ms and TE = 0.9 ms. T1 and M0 maps will be
computed using image data using an L-M fitting algorithm according to the steady state
signal equation.
Perfusion images will be acquired using a time-resolved, spoiled GE sequence with 1×1×2 mm
spatial resolution, approximately one second 3D temporal resolution, and image
technique/contrast parameters TR = 2.8 ms and TE = 0.9 ms. Upon commencement of the scan,
0.05 ml/kg of Gadovist (at 4 ml/s) and 20 ml of saline flush (also at 4 ml/s) will be
administered. Approximately three minutes after scan commencement, the salivary glands will
be stimulated by orally administering a small portion (≈5 ml) of lemon juice. Total
perfusion scan time is expected to be 10 minutes, and the superior/inferior scan length will
chosen to encompass both the parotid and submandibular glands.
Time dependent concentration maps will be derived from perfusion images and both
pre-contrast T1 and M0 maps. An "extended Kety"-type model will be fit to the data with the
intent of extracting the following physiologically-descriptive quantities ('metrics'): the
volume of plasma/volume of tissue (νp), Apparent Diffusion Coefficient (ADC), the volume of
extracellular extravascular space per volume of tissue (νe), and the contrast agent transfer
coefficients (Ktrans).
Equipment 2% citric Acid will be delivered to the oral cavity via a syringe and Tygon tubing
at two separate time intervals in order to stimulate the parotid gland.
EVALUATION DURING AND AFTER PROTOCOL TREATMENT
A trained medical personnel will be present during the MRI procedure to ensure patient
safety is maintained through out. After the scan is completed the volunteer will not be
required to attend any further follow up appointments.
ADVERSE EVENTS
Definition of a Reportable Serious Adverse Event
All serious adverse events which are unexpected and related to protocol Investigation must
be reported in an expedited manner (see Section 11.2 for reporting instructions). These
include events occurring during the MRI scan (until 30 days after) and at any time
afterwards.
Unexpected adverse events are those which are not consistent in either nature or severity
with information contained in the product monograph or package insert.
Adverse events considered related to protocol investigation are those for which a
relationship to the protocol investigation cannot reasonably be ruled out.
A serious adverse event (SAE) is any adverse event that: results in death, is
life-threatening,requires inpatient hospitalization or prolongation of existing
hospitalization (excluding hospital admissions for study drug administration, transfusions,
scheduled elective surgery and admissions for palliative or terminal care),results in
persistent or significant disability or incapacity or is a congenital anomaly/birth defect
Medical and scientific judgement should be exercised in deciding whether expedited reporting
is appropriate in other situations such as important medical events that may not be
immediately life-threatening or result in death or hospitalization but may jeopardize the
subject or may require intervention to prevent one of the events listed above.
Serious Adverse Event Reporting Instructions
All reportable serious adverse events must be reported within 3 days to the Research Ethics
Board.
PROTOCOL DISCONTINUATION
Criteria for Discontinuing Protocol Treatment
participants may stop protocol if: Intercurrent illness Unacceptable toxicity as defined in
Section 14.4 Request by the subject
Safety Monitoring Adverse events to the contrast agent (Gadovist) will be monitored on an
ongoing basis by the study team.
Any grade 5 toxicity (death) that is possibly, probably or definitely caused by the contrast
agent will result in suspension of accrual and investigation by the investigator team.
Any life threatening reactions or Nephrogenic Systemic fibrosis will result in suspension of
accrual and investigation by the investigator team.
Although the images will not be formally reviewed by a radiologist, it is possible that the
imaging may identify unexpected abnormalities. The participants will not be issued with a
diagnostic report however if an abnormality is detected, the participants and their general
practitioner (with the participants permission) will be informed so that further
investigations and appropriate referral can be made.
