Peripheral Neuropathic PainNCT01293851
Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Nerve Damage
An observational study of Peripheral Neuropathic Pain and Neurotoxicity, run by National Institute of Nursing Research (NINR) at 1 site in United States.
Trial summary
Background: Docetaxel, the most commonly used drug for the treatment of invasive breast cancer, has been shown to prolong the lives of women with breast cancer and prevent the cancer from spreading or returning. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peripheral Neuropathic Pain, Neurotoxicity, Cancer
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Dec 2010to 13 Nov 2012
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 analyses.
- Ability to provide informed consent
- Cancer patients scheduled to undergo chemotherapy with taxane class, vinca alkaloid class, platinum compounds or bortezomib
Who cannot join
- 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
Show all 21Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression
Background:
- Docetaxel, the most commonly used drug for the treatment of invasive breast cancer, has been shown to prolong the lives of women with breast cancer and prevent the cancer from spreading or returning. However, docetaxel is known to cause nerve damage, including numbness, tingling, and pain, in 50 to 90 percent of breast cancer patients. This nerve damage is called peripheral neuropathy, and can be so severe that treatment with docetaxel may need to be stopped. Researchers are interested in studying docetaxel-related nerve damage to determine whether certain genetic factors may predispose women to developing this condition, and to more closely investigate the specific effects of docetaxel on the nervous system
Read more
Objectives:
- To examine nerve damage in women with breast cancer who are being treated with docetaxel.
Eligibility:
- Women at least 18 years of age who have been diagnosed with invasive breast cancer and are scheduled to have docetaxel treatment.
Design:
- Participants will be screened with a full medical history and physical examination, as well as blood and urine tests and imaging studies.
- This study requires seven visits, one before the start of chemotherapy and six after the scheduled treatment visits. Study procedures at each visit will take 30 to 45 minutes and will be done in parallel with scheduled chemotherapy visits.
- At the first visit, participants will provide blood samples; complete questionnaires to rate and describe any existing pain, numbness, or tingling in hands and feet before the start of chemotherapy; have nerve conduction tests; and have a skin biopsy.
- At each visit following docetaxel treatment, participants will complete questionnaires to rate and describe any pain, numbness, or tingling during the course of chemotherapy. Participants will provide blood samples at every visit and have nerve conduction tests during the second, fourth, and sixth visits. Participants will also have a second skin biopsy, either from a site that appears to be experiencing nerve damage or (for those who are not developing nerve damage symptoms) from a site near the first biopsy location.
Read the detailed description
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 symptoms.
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.
- Conditions
- Peripheral Neuropathic Pain, Neurotoxicity, Cancer
- Keywords
- Biomarkers, Gene Expression, Neuropathic Pain, Neurotoxicity, Chemotherapy, Peripheral Neuropathic Pain, Cancer
- Medical subject headings
- Neurotoxicity Syndromes, Neoplasms, Neuralgia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2011 (estimated)
- Study start22 Dec 2010
- Study completion13 Nov 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Peripheral Neuropathic PainStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Time perspective
- Prospective
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Institute of Nursing Research (NINR)
- Sponsor type
- US National Institutes of Health
- Investigators
- Xiao Min Wang, M.D., Principal investigator, National Institute of Nursing Research (NINR)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01293851
- Sponsor's protocol ID
- 110065
- Other IDs
- 11-NR-0065
- Status last verified
- 13 Nov 2012
- First submitted
- 25 Jan 2011
- Last updated
- 5 Dec 2019
- Results posted
- No
Publications
Hoyert DL, Heron MP, Murphy SL, Kung HC. Deaths: final data for 2003. Natl Vital Stat Rep. 2006 Apr 19;54(13):1-120.
PubMed 16689256Thase ME, Frank E, Mallinger AG, Hamer T, Kupfer DJ. Treatment of imipramine-resistant recurrent depression, III: Efficacy of monoamine oxidase inhibitors. J Clin Psychiatry. 1992 Jan;53(1):5-11.
PubMed 1737741Cmelak AJ, Murphy BA, Burkey B, Douglas S, Shyr Y, Netterville J. Taxane-based chemoirradiation for organ preservation with locally advanced head and neck cancer: results of a phase II multi-institutional trial. Head Neck. 2007 Apr;29(4):315-24. doi: 10.1002/hed.20522.
PubMed 17252600
Study at a glance
From the registry record, last updated by the sponsor on 5 Dec 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterization of the Molecular-Genetic Mechanisms Associated With Chemotherapy-Induced Peripheral Neuropathy Progression
- ClinicalTrials.gov ID
- NCT01293851
- Acronym / sponsor ID
- 110065
- Conditions
- Peripheral Neuropathic Pain, Neurotoxicity, Cancer
- Keywords
- Biomarkers, Gene Expression, Neuropathic Pain, Neurotoxicity, Chemotherapy, Peripheral Neuropathic Pain, Cancer
- Study type
- Observational
- Recruitment status
- Terminated
- Enrolment
- 3 participants (actual)
- Lead sponsor
- National Institute of Nursing Research (NINR)US National Institutes of Health
- Study start
- 22 Dec 2010
- Study completion
- 13 Nov 2012
- First posted
- 11 Feb 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Docetaxel, the most commonly used drug for the treatment of invasive breast cancer, has been shown to prolong the lives of women with breast cancer and prevent the cancer from spreading or returning. However, docetaxel is known to cause nerve damage, including numbness, tingling, and pain, in 50 to 90 percent of breast cancer patients. This nerve damage is called peripheral neuropathy, and can be so severe that treatment with docetaxel may need to be stopped. Researchers are interested in studying docetaxel-related nerve damage to determine whether certain genetic factors may predispose women to developing this condition, and to more closely investigate the specific effects of docetaxel on the nervous system
Objectives:
- To examine nerve damage in women with breast cancer who are being treated with docetaxel.
Eligibility:
- Women at least 18 years of age who have been diagnosed with invasive breast cancer and are scheduled to have docetaxel treatment.
Design:
- Participants will be screened with a full medical history and physical examination, as well as blood and urine tests and imaging studies.
- This study requires seven visits, one before the start of chemotherapy and six after the scheduled treatment visits. Study procedures at each visit will take 30 to 45 minutes and will be done in parallel with scheduled chemotherapy visits.
- At the first visit, participants will provide blood samples; complete questionnaires to rate and describe any existing pain, numbness, or tingling in hands and feet before the start of chemotherapy; have nerve conduction tests; and have a skin biopsy.
- At each visit following docetaxel treatment, participants will complete questionnaires to rate and describe any pain, numbness, or tingling during the course of chemotherapy. Participants will provide blood samples at every visit and have nerve conduction tests during the second, fourth, and sixth visits. Participants will also have a second skin biopsy, either from a site that appears to be experiencing nerve damage or (for those who are not developing nerve damage symptoms) from a site near the first biopsy location.
Detailed description
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 symptoms.
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.
Study design
- Time perspective
- Prospective
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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 analyses.
- Ability to provide informed consent
- Cancer patients scheduled to undergo chemotherapy with taxane class, vinca alkaloid class, platinum compounds or bortezomib
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
Results and safety
The study was stopped early. Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Dec 2019.
- Background: PubMed 16689256Hoyert DL, Heron MP, Murphy SL, Kung HC. Deaths: final data for 2003. Natl Vital Stat Rep. 2006 Apr 19;54(13):1-120.
- Background: PubMed 1737741Thase ME, Frank E, Mallinger AG, Hamer T, Kupfer DJ. Treatment of imipramine-resistant recurrent depression, III: Efficacy of monoamine oxidase inhibitors. J Clin Psychiatry. 1992 Jan;53(1):5-11.
- Background: PubMed 17252600Cmelak AJ, Murphy BA, Burkey B, Douglas S, Shyr Y, Netterville J. Taxane-based chemoirradiation for organ preservation with locally advanced head and neck cancer: results of a phase II multi-institutional trial. Head Neck. 2007 Apr;29(4):315-24. doi: 10.1002/hed.20522.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Xiao Min Wang, M.D. principal investigator
National Institute of Nursing Research (NINR)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Peripheral Neuropathic Pain and Neurotoxicity, run by National Institute of Nursing Research (NINR) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 5 Dec 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early. Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01293851, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Dec 2019.