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Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression

18 Years
Not Enrolling
Peripheral Neuropathic Pain, Neurotoxicity, Cancer

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Trial Information

Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression

Objective: Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most debilitating
side effects of neurotoxic chemotherapy, and can significantly interfere with patient
quality of life (QOL) and the administration of antineoplastic therapy. There is no
currently approved safe and effective treatment for CIPN. This protocol will explore the
molecular-genetic mechanisms associated with the natural history of CIPN progression by (1)
identification of differentially expressed genes and proteins as biomarkers for the onset of
CIPN; (2) evaluation of the relationship between biomarkers and the severity of CIPN during
the observation period, and (3) determining the relationship between molecular-genetic
biomarkers, morphological changes in small nerve fiber and the severity of neuropathic

Study population: Cancer patients who plan to receive chemotherapy treatment with either
taxane class, vinca alkaloid class, platinum compounds or bortezomib.

Design: This is a prospective, exploratory, natural history study to identify the
molecular-genetic mechanisms involved in chemotherapy-induced neuropathy in cancer patients.
A physician-based neuropathy scale, patient neurotoxocity questionnaire, and the total
neuropathy score will be used to measure the severity of peripheral neuropathy at baseline
and after completion of each cycle of chemotherapy infusion. Whole peripheral blood and skin
biopsy (only from patients who consent to biopsies) will be collected at baseline and after
a subsequent infusion cycle to evaluate gene/protein expression and immunohistochemical
labeling at peripheral sites of neuropathic injury. Microarray gene expression analysis will
be employed to identify differential regulation of genes involved in the development of CIPN
at the different time points compared with gene expression from the baseline samples. Genes
of interest will be validated by qRT-PCR to identify novel pharmacological targets to be
evaluated in future prospective studies. Protein levels corresponding to the changes in gene
expression will be evaluated using ELISA and verified by Western blotting.

Outcome measures: The primary outcome of the study will be the changes in gene and protein
expression in the peripheral blood and skin biopsy among cancer patients undergoing
chemotherapy. The secondary outcome will be the relationship between the molecular-genetic
biomarkers identified and the presence of peripheral neuropathic symptoms and their impacts
on patient's QOL.

Inclusion Criteria


Patients must meet all of the following to be eligible for enrollment:

- Age: 18 years and older

- Both male and female cancer patients will be recruited in this study. However, data
will be separately assessed between males and females due to the differences in
incidence, etiology and hormonal dependence which may confound the final data

- Ability to provide informed consent

- Cancer patients scheduled to undergo chemotherapy with taxane class, vinca alkaloid
class, platinum compounds or bortezomib


- Patients with any one of the following will be excluded:

- Unable to provide their own informed consent

- Have had prior radiotherapy

- Pre-existing documented neuropathy or risk factors for neuropathy that may confound
the analysis of factors associated with CIPN such as:

- Diabetes mellitus

- Uremia

- Vitamin B12 deficiency

- Peripheral vascular disease

- Documented Thyroid dysfunction with on-going treatment. The patients who have thyroid
dysfunction may also manifest the peripheral neuropathic symptoms such as numbness
and tingling on their feet and hands. The medications used to treat hypothyroidism
may confound the study data assessment.

- Previous history of alcoholism (beriberi) or drug abuse

- Rheumatoid arthritis

- Lupus

- Amyloidosis

- Sarcoidosis

- Other drug-induced neuropathy that may confound the analysis associated with CIPN
such as:

- Thalidomide

- Isoniazid

- Trichloroethylene

- Hydralazine

- Disulfiram

- Nitrofurantoin

Type of Study:


Study Design:

Time Perspective: Prospective

Principal Investigator

Leorey N Saligan, C.R.N.P.

Investigator Role:

Principal Investigator

Investigator Affiliation:

National Institute of Nursing Research (NINR)


United States: Federal Government

Study ID:




Start Date:

December 2010

Completion Date:

November 2012

Related Keywords:

  • Peripheral Neuropathic Pain
  • Neurotoxicity
  • Cancer
  • Biomarkers
  • Gene Expression
  • Neuropathic Pain
  • Neurotoxicity
  • Chemotherapy
  • Peripheral Neuropathic Pain
  • Cancer
  • Neuralgia
  • Peripheral Nervous System Diseases
  • Neurotoxicity Syndromes



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