Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03348956 |
| Other study ID # |
D17062 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
March 1, 2018 |
| Est. completion date |
February 14, 2022 |
Study information
| Verified date |
April 2023 |
| Source |
Dartmouth-Hitchcock Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
This pilot study will attempt to establish the feasibility of using tissue oxygen
measurements and the protein, neurofilament light chain (NF-L), as potential biomarkers for
chemotherapy-induced peripheral neuropathy (CIPN). Thirty (30) subjects scheduled to begin
taxane-based chemotherapy for breast tumor will be assigned to receive an India ink injection
under the skin of the foot. The ink will be used to make up to five (5) 45-minute "electron
paramagnetic resonance" (EPR) oximetry readings prior to the start of chemotherapy. Subjects
will undergo electrophysiologic assessments including nerve conduction studies, in addition
to a neurological examination prior to the start of chemotherapy. Subjects will have the EPR
oximetry readings, electrophysiologic tests, and neurological examination two more times: at
the halfway point of their chemotherapy treatment -- or at the onset of CIPN symptoms -- and
again after chemotherapy has been completed. Subjects will also have blood drawn prior to
beginning taxane-based chemotherapy, prior to every scheduled chemotherapy treatment, and
after completion of chemotherapy in order to test for neurofilament light chain (NF-L).
Description:
Therapy with chemotherapeutic drugs can make a huge impact on survival and quality of life in
patients with cancer. Advances in medical monitoring and the effectiveness of these therapies
have significantly improved outcomes so that a definitive cure or long-term survival is more
likely. Cancer survivors are used to dealing with serious side effects of their therapy;
however, some of the side effects from the chemotherapy drugs persist even after the
medication course is completed. The impact of these sequelae on quality of survival is
increasingly being appreciated and forming an important new direction of cancer care. One of
the more severe side effects of chemotherapy is peripheral neurotoxicity resulting in
neuropathy or neuronopathy.
Chemotherapy-induced peripheral neurotoxicity (CIPN) is one of the least predictable and most
prolonged sequelae with effects ranging from pain, numbness and tingling to diffuse weakness
sometimes to the extent of paralysis. It results from damage or alteration in function of
peripheral nerves usually, but not always, in a length-dependent manner. An indirect impact
of CIPN includes difficulties with balance and susceptibility to falls. There are currently
no therapies that have been proven to prevent CIPN. Similarly, there are few medications that
are known to be effective in the reversing CIPN once it develops or effectively treating
symptoms of CIPN. Currently, diagnosis is based mainly on clinical examination and
electrophysiological testing to monitor CIPN; identification of candidate biomarkers through
which disease onset can be identified at an earlier stage and which reflect presumed
pathophysiologic mechanisms is of paramount importance.
There are different theories of CIPN pathogenesis. One of the leading hypotheses relates to
mitochondrial dysfunction and oxidative stress affecting both the dorsal root ganglia neurons
and supportive endothelial cells of the vasa nervorum. Here at Dartmouth, a specialized
technique has been developed that allows the non-invasive assessment of tissue oxygen in and
around peripheral nerve. This technique, called "electron paramagnetic resonance" (EPR)
oximetry, allows for repeated measurements over time that can be correlated with other
metrics of peripheral nerve function. Given its relevance to an important pathophysiologic
mechanism of disease, EPR oximetry may provide an early marker of disease onset.
Neurofilament light chain (NF-L) is also emerging as a sensitive blood-based biomarker of
axonal degeneration. NF-L is a component of the axonal cytoskeleton that leaks out of
degenerating axons. NF-L has been reported to be elevated in plasma or serum in a wide range
of neurodegenerative disorders, including CNS disorders such as multiple sclerosis and ALS as
well as PNS disorders such as Charcot Marie Tooth and Guillain-Barre syndrome. To date, there
are no published reports of elevated blood NF-L levels in patients with CIPN, although it has
been reported to increase in rat model of vincristine-induced neuropathy.
In this proposal, the investigators will be testing the hypothesis that these could both be
biomarkers of CIPN. It is hoped that the oximetry measurement and blood NF-L levels will (i)
reflect the changes that occur on a cellular level and the damaged nerves, (ii) reflect the
damage occurring to nerves more sensitively than existing techniques, and (iii) help to
better understand the reason the nerves are being damaged. It is also hoped that these will
be something that can be used in future clinical trials.
