Ultrasound for Detecting Chemotherapy-Induced Peripheral Neuropathy

Overseen By Ashley Fansler, RN

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Wake Forest University Health Sciences

Must be taking: Oxaliplatin

Disqualifiers: Pre-existing neuropathy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 1

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of ultrasound in detecting nerve damage caused by the chemotherapy drug oxaliplatin (Eloxatin) in individuals with gastrointestinal cancer. The goal is to determine if ultrasound provides a better diagnosis for nerve problems experienced by some patients during treatment. This trial suits those with gastrointestinal cancer who are receiving or have received oxaliplatin-based chemotherapy and have symptoms of nerve damage, such as tingling or numbness. As an unphased trial, it offers a unique opportunity to contribute to research that could enhance diagnostic methods for nerve damage.

Do I have to stop taking my current medications for this trial?

The protocol does not specify if you need to stop taking your current medications.

What prior data suggests that ultrasound is safe for detecting neuropathy?

Research shows that oxaliplatin, a chemotherapy drug, can cause peripheral neuropathy, a type of nerve damage. This common side effect often results in numbness or tingling, particularly in the hands and feet. Cold temperatures can intensify these sensations for some individuals. This nerve damage may continue to worsen for a few months even after treatment ends.

Studies have found that patients taking oxaliplatin often experience more numbness than those on other treatments. Although nerve damage is a significant concern, patients should know that this side effect is well-documented and closely monitored during treatment. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using ultrasound to detect chemotherapy-induced peripheral neuropathy because it offers a non-invasive way to monitor nerve health. Unlike current methods, which often rely on symptom reporting or invasive nerve conduction studies, ultrasound can provide real-time images of peripheral nerves. This technique has the potential to improve early detection and intervention, which could help manage symptoms more effectively and enhance patients' quality of life during chemotherapy.

What evidence suggests that ultrasound is effective for detecting chemotherapy-induced neuropathy?

Research has shown that ultrasound holds promise for spotting nerve damage caused by chemotherapy. In this trial, participants will undergo peripheral nerve ultrasound to detect changes in nerves due to chemotherapy drugs like oxaliplatin. Understanding these nerve changes is crucial for better symptom management. Although some research suggests ultrasound might also help with chemotherapy-related pain, this trial focuses on detection. Overall, ultrasound is proving useful in helping doctors see how chemotherapy affects nerves more clearly. ^{6 7 8 9 10}

Who Is on the Research Team?

Roy E. Strowd

Principal Investigator

Wake Forest University Health Sciences

Are You a Good Fit for This Trial?

This trial is for patients with any stage of gastrointestinal or colorectal cancer who are currently or have previously been treated with oxaliplatin-based chemotherapy and now show signs of peripheral neuropathy. Participants must be able to understand and sign a consent form.

Inclusion Criteria

I have cancer in my digestive system.

I am currently or have previously been treated with oxaliplatin-based chemotherapy.

I have been diagnosed with colorectal cancer.

Exclusion Criteria

I cannot provide my medical or treatment history.

I had nerve damage in my hands or feet before starting oxaliplatin chemotherapy.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Ultrasound Assessment

Participants undergo peripheral nerve ultrasound to assess nerve cross-sectional area

Up to 30 days

1 visit (in-person)

Follow-up

Participants are monitored for changes in nerve conduction and neuropathy symptoms

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Oxaliplatin
• Ultrasound - Serial and Tibial Nerve

Trial Overview The study is testing the effectiveness of ultrasound in detecting neuropathy caused by oxaliplatin in gastrointestinal cancer patients. It involves nerve exams, skin biopsies, nerve conduction studies, blood draws, and questionnaires about chemotherapy-induced peripheral neuropathy.

How Is the Trial Designed?

Group I: Ultrasound Experimental Treatment 6 Interventions

Undergo peripheral nerve ultrasound

Oxaliplatin is already approved in European Union, United States, Canada, Japan, Switzerland, China for the following indications:

Approved in European Union as Eloxatin for:

• Colorectal cancer

Approved in United States as Eloxatin for:

• Colorectal cancer

Approved in Canada as Eloxatin for:

• Colorectal cancer

Approved in Japan as Eloxatin for:

• Colorectal cancer

Approved in Switzerland as Eloxatin for:

• Colorectal cancer

Approved in China as Ai Heng for:

• Colorectal cancer

Who Is Running the Clinical Trial?

Wake Forest University Health Sciences

Lead Sponsor

Trials

1,432

Recruited

2,506,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

In a study of 15 breast cancer patients undergoing paclitaxel treatment, clinical examinations revealed a significant increase in total neuropathy scores, indicating the development of taxane-induced polyneuropathy (TIPN) over time, particularly noticeable by 8 weeks after treatment.

High-resolution nerve ultrasound (HRUS) and nerve conduction studies (NCS) were able to detect changes in nerve structure and function after 6 months, but corneal confocal microscopy (CCM) did not show early signs of TIPN, suggesting that clinical assessments remain the most effective method for early detection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-resolution nerve ultrasound and corneal confocal microscopy in taxane-induced polyneuropathy. Katz, M., Mork, H., Baghdasaryan, N., et al.[2023]

Low-intensity pulsed low-frequency ultrasound treatment significantly improved symptoms of cisplatin-induced peripheral neuropathy in rats, enhancing pain perception and nerve conduction after 15 days of treatment.

The ultrasound therapy also reduced oxidative stress and inflammation, restored nerve structure, and regulated apoptosis, indicating its potential as an effective intervention for chemotherapy-related nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity low-frequency pulsed ultrasound ameliorates sciatic nerve dysfunction in a rat model of cisplatin-induced peripheral neuropathy. Bilir-Yildiz, B., Sunay, FB., Yilmaz, HF., et al.[2022]

In a study of 186 cancer patients undergoing oxaliplatin treatment, factors such as age, gender, and performance status were significantly associated with the development of severe oxaliplatin-induced peripheral neuropathy (OIPN).

Serum levels of gamma-glutamyl transferase (GGT), vitamin D, and hemoglobin were identified as key predictors for the severity of OIPN, suggesting that these easily obtainable clinical parameters could help in assessing risk before treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Predictive clinical factors of chronic peripheral neuropathy induced by oxaliplatin. Yildirim, N., Cengiz, M.[2021]

Chemotherapy and immunotherapy can lead to peripheral neuropathies in cancer patients, making it crucial to differentiate these from other neurological issues, which is currently challenging.

Neuromuscular ultrasound (NMUS) has shown promise as a diagnostic tool for identifying treatment-induced peripheral neurotoxicity, with new findings indicating it can detect changes in dorsal roots associated with both cytostatic and immunotherapy-induced nerve damage.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of neuromuscular ultrasound in diagnostics of peripheral neuropathies induced by cytostatic agents or immunotherapies. Hartinger, S., Hammersen, J., Leistner, NA., et al.[2023]

In a study of 20 breast cancer patients experiencing moderate chemotherapy-induced peripheral neuropathy (CIPN) after taxane treatment, neuromuscular ultrasound (NMUS) revealed that the sural nerve cross-sectional area (CSA) was significantly smaller compared to healthy controls, indicating nerve damage.

The findings suggest a sensory predominant neuropathy, as a decrease in sural nerve CSA correlated with a reduction in intraepidermal nerve fiber density, highlighting the potential of NMUS as a tool for assessing CIPN and the need for further longitudinal studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Neuromuscular ultrasound for taxane peripheral neuropathy in breast cancer. Lycan, TW., Hsu, FC., Ahn, CS., et al.[2021]

In a study involving 17 patients undergoing oxaliplatin chemotherapy, vibration perception threshold (VPT) was identified as the most sensitive early marker of oxaliplatin-related neuropathy, indicating its effectiveness for monitoring at low drug doses.

While nerve excitability studies showed potential for predicting neuropathy, they did not reveal significant early changes in motor axons, suggesting that VPT is a more reliable and practical tool for early detection of sensory neuropathy in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electroclinical biomarkers of early peripheral neurotoxicity from oxaliplatin. McHugh, JC., Tryfonopoulos, D., Fennelly, D., et al.[2019]

In a study of 1313 patients with stage III colon cancer, a 3-month course of oxaliplatin-based chemotherapy significantly reduced the incidence of long-lasting peripheral sensory neuropathy (PSN) compared to a 6-month course (9.7% vs 24.3%).

The 3-month treatment duration did not compromise disease-free survival (DFS) outcomes, suggesting that a shorter course, particularly with the CAPOX regimen, may be a safer and effective option for patients, especially those with low-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. Yoshino, T., Yamanaka, T., Oki, E., et al.[2022]

In a study of 15 colorectal cancer patients undergoing oxaliplatin (OXL) treatment, 86.7% developed sensory axonal neuropathy, indicating that this is a common and significant side effect of OXL therapy.

Ultrasound analysis revealed increased cross-sectional area of the median and ulnar nerves at entrapment sites in 60% of patients, suggesting that OXL may increase nerve susceptibility to mechanical damage, even in those without prior neuropathy symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound assessment of oxaliplatin-induced neuropathy and correlations with neurophysiologic findings. Briani, C., Campagnolo, M., Lucchetta, M., et al.[2018]

In a study of 126 women treated with taxane-based chemotherapy for breast cancer, 73% reported experiencing chemotherapy-induced peripheral neuropathy (CIPN), which significantly affected their quality of life and physical functioning.

CIPN severity was notably higher in Black or African American women, indicating a need for targeted screening and intervention strategies to address this disparity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The prevalence and pattern of chemotherapy-induced peripheral neuropathy among women with breast cancer receiving care in a large community oncology practice. Simon, NB., Danso, MA., Alberico, TA., et al.[2022]

Citations

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Preliminary effects of low-intensity focused ultrasound ... To evaluate the effectiveness of low-intensity focused ultrasound (LIFU) therapy in the management of cancer-related neuropathic pain (CNP).

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02499939

Study Details | NCT02499939 | Ultrasound Therapy and ... The primary purpose of the trial is to determine the preliminary efficacy of therapeutic ultrasound in the treatment of pain and sensory disturbance related to ...

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Therapeutic Ultrasound for Chemotherapy-Related Pain ... The aim of this study was to determine the feasibility and preliminary efficacy of adding therapeutic ultrasound to a home-based therapeutic exercise program ( ...

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The role of neuromuscular ultrasound in diagnostics of ... Chemotherapy-induced peripheral neuropathy (CIPN) is a relevant dose-limiting toxicity of several anticancer treatment regimens. In most ...

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Ultrasound may have potential for treating pain after ... Participants had improvements in symptoms of pain and sensory disturbance after two weeks of treatment with therapeutic ultrasound.

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Management of oxaliplatin-induced peripheral neuropathy Neurotoxicity is the most frequent dose-limiting toxicity of oxaliplatin. Acute sensory neurotoxicity manifests as rapid onset of cold-induced distal ...

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Chemotherapy-induced peripheral neuropathy (CIPN) L-Carnosine protects against Oxaliplatin-induced peripheral neuropathy in colorectal cancer patients: A perspective on targeting Nrf-2 and NF-kappaB ...

8. ascopubs.org ascopubs.org/doi/10.1200/JCO.20.01399

Prevention and Management of Chemotherapy-Induced ... In contrast, oxaliplatin-induced neuropathy, on average, worsens for 2-3 months after cessation of therapy (labeled as coasting phenomenon); ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0304383524008280

An emerging aspect of cancer neuroscience: A literature ... Chemotherapy-induced peripheral neuropathy (CIPN) is the most common side effects that significantly reduce the efficacy of anti-cancer treatment and patients' ...

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Patterns of Patient-Reported Chemotherapy-Induced ... Mean patient-reported numbness was significantly higher in those who received oxaliplatin-containing chemotherapy (mean, 3.31) compared with fluoropyrimidines ...