Chemotherapy-induced Peripheral Neuropathy (CIPN)

This is a Phase 1, first-in-human (FIH), randomized, double-blind, placebo-controlled, parallel-group, single ascending dose (SAD) study to evaluate the safety, tolerability, and pharmacokinetics of AH-008 administered as a single intravenous infusion in healthy adult subjects. Four sequential dose cohorts will be evaluated, each with sentinel dosing and SRC-reviewed dose escalation.

Chemotherapy drugs, used in the treatment of cancer, have the potential of inducing peripheral neuropathy (PN) as a side effect. This side effect is commonly referred to as CIPN, or chemotherapy-induced peripheral neuropathy. The Lilac Glove and Boot devices apply a low pressure across the surface of the hands and feet, respectively, to reduce access of chemotherapy to the peripheral nerves on the hands and feet. The small amount of pressure reduces the level of chemotherapy reaching the peripheral nerves, hence increasing the likelihood of nerve preservation during treatment and thus may potentially temporarily prevent the onset of moderate to severe PN symptoms induced by chemotherapy in the hands and feet while receiving treatment

The purpose of this study is to determine the effectiveness of the EX-CIPN program in reducing the strength of CIPN symptoms and CIPN-related disability and improving the ability to complete everyday activities. This will be done by determining whether it is better to receive the EX-CIPN program or better to receive no additional intervention. To do this, some of the participants in this study will get EX-CIPN and others will receive usual care. Those who receive usual care will be offered EX-CIPN upon study completion. The main question it aims to answer is: • Is EX-CIPN effective in improving CIPN symptoms for cancer survivors experiencing persistent CIPN? Participants in both study groups will be asked to: • Complete assessments at baseline, immediately post-intervention, and 3-months post-intervention Participants in the EX-CIPN group will be asked to: * Complete an additional aassessment at 6-months post-intervention * Complete a 10-week remote, individualized exercise program * Receive health coaching calls on weeks 2, 3, 4, 6, and 8 of the intervention * Wear a FitBit throughout the study to track physical activity and promote behaviour change

Chemotherapy-induced peripheral neuropathy (CIPN) is a frequent and debilitating side effect of many cancer treatments. It affects 28 to 48% of patients receiving chemotherapy. Symptoms include tingling, numbness, burning sensations, and pain mainly in the hands and feet. While CIPN often improves after chemotherapy ends, in some patients the pain persists and becomes chronic, severely impairing quality of life, sleep, and daily functioning. Currently, no treatment has been shown to prevent CIPN. For patients with chronic pain, duloxetine is the only recommended drug, but its efficacy is limited. When standard medications fail, patients have very few options. Spinal cord stimulation (SCS) is a well-established neurosurgical technique used to treat various forms of chronic neuropathic pain, including pain after surgery, trauma, or diabetes. In this procedure, thin electrodes are placed in the epidural space near the spinal cord and connected to a small implantable pulse generator. The electrical impulses delivered by the device modulate pain signals in the nervous system. Preliminary case reports suggest that SCS may be effective in patients with CIPN, but no randomized controlled trial has yet established its value in this specific indication. The CHEMOSTIM study aims to fill this gap. CHEMOSTIM is a multicenter, prospective, randomized crossover trial. All enrolled patients will undergo SCS implantation. Participants will then be randomized to receive either active stimulation first followed by sham stimulation, or sham stimulation first followed by active stimulation. In the sham phase, the device is implanted but switched off following a simulated programming session, so patients cannot tell which phase they are in. The primary outcome is the proportion of patients achieving more than 50% pain reduction on a Visual Analog Scale (VAS) during the active stimulation phase compared to the sham stimulation phase, assessed at 4 months. Secondary outcomes include changes in quality of life, anxiety and depression, sleep quality, medication use, individualized goal attainment, neurological examination, and nerve conduction studies. The study will also evaluate post-stimulation effects and complications. Eligible patients are adults with chronic CIPN evolving for at least one year, with pain greater than 5/10 in the lower limbs, who have failed at least two lines of pharmacological treatment (antidepressants, anticonvulsants, topical agents, etc.) and whose indication for SCS has been validated by a multidisciplinary team following SFETD/SFNM guidelines.

The goal of this clinical trial is to determine whether quantitative sensory testing (QST) can be used to classify participants into pain sub-groups and predict who will respond best to certain pain treatments in participants with painful peripheral neuropathy. The analgesic effect is evaluated by measuring pain intensity and Patient Global Impression of Change (PGIC). This study is a 3-period cross-over trial. This means researchers will compare 3 different drugs (pregabalin, duloxetine, and placebo) over a period of 19 weeks. Participants will: * Undergo a quantitative sensory testing (QST) exam. * Provide a blood sample. * Complete questionnaires on the computer. * Take the study drug as instructed.

This prospective, randomised, controlled study was designed to evaluate the effectiveness of salt and unsalted cold water foot baths in preventing chemotherapy-induced peripheral neuropathy (CIPN) in patients receiving paclitaxel. The study's sub-objectives were to minimise the development of CIPN, reduce its severity and incidence of symptoms, and minimise its impact on daily life and activities. Hypothesis(es): H1: Salt cold water foot bath affects the development of chemotherapy-induced peripheral neuropathy. H2: There is an effect of unsalted cold water foot bath on the development of chemotherapy-induced peripheral neuropathy. H3: The effects of salt and unsalted cold water foot baths on the development of chemotherapy-induced peripheral neuropathy. H4: Salt and unsalted cold water foot baths are more effective than standard clinical care in the development of chemotherapy-induced peripheral neuropathy. Researchers will compare the salt cold water with the unsalted cold water, unsalted cold water and control group to determine whether the salt cold water has an effect on CIPN. The experimental group and active comparator participants will continue the application for 12 cycles (12 weeks) of paclitaxel. The application will be applied by researcher Tuba Eryiğit. In addition, before each application for 12 weeks, the severity of CIPN, its effect on daily life and grade will be evaluated. The control group will continue clinical routine care applications for 12 cycles (12 weeks). In addition, the severity of CIPN, its effect on daily life and grade will be evaluated before each treatment in the same way as the experimental groups.

The goal of this clinical trial is to evaluate the efficacy of Whole-body vibration in improving postural control, risk of falling, and quality of life in patients with chemotherapy-induced peripheral neuropathy. The main questions it aims to answer are: Does Whole-body vibration have a significant effect on postural control, risk of falling, and quality of life in patients with chemotherapy-induced peripheral neuropathy? Researchers will compare whole body vibration in addition to traditional exercise to traditional exercise alone to see if Whole-body vibration have a significant effect on postural control, risk of falling, and quality of life in patients with chemotherapy-induced peripheral neuropathy. Participants will: * age between 30-60 years old. * be on chemotherapy for at least one cycle as a treatment of malignant tumors with peripheral neuropathy. * have mild to moderate neuropathy according to mTNS. * be assigned randomly into two equal groups (control group (A) and study group (B)). * Take three sessions per week for eight weeks. * The control group (A) will be treated by selected physical therapy treatment (Strength resistive training, Stretching \& flexibility, Balance training) * The study group (B) will be treated with selected physical therapy treatment in addition to whole-body vibration therapy.

The purpose of this observational, data collection, research is to evaluate if ziconotide, a commercially approved medication given by a FDA cleared intrathecal pump, for chronic pain is effective in the treatment of chemotherapy-induced peripheral neuropathy (CIPN) a common and often long-lasting side effect of cancer treatment.

Great Toe Strength (GTS) is a potential clinical biomarker that has been associated with functional mobility and health; Additionally, GTS has been identified in the literature as one of the early symptoms of chemotherapy-induced peripheral neuropathy (CIPN). The purpose of this research study is to evaluate GTS in individuals with CIPN and healthy adults using ToeScale and see how it relates to nerve issues from chemotherapy. Additionally, we aim to assess the usability of the novel GTS assessment device, ToeScale among the participants. As a part of this study visit, you will complete some questionnaires followed by GTS and balance and gait assessments.

As a core component of comprehensive breast cancer treatment, chemotherapy frequently induces chemotherapy-induced peripheral neuropathy (CIPN), particularly with taxane-based agents. The incidence of CIPN reaches 68.1% within the first month of chemotherapy, and over 30% of patients experience persistent symptoms for more than 6 months. The resulting sensorimotor dysfunction significantly impairs patients' quality of life, necessitates dose reduction or treatment discontinuation, and ultimately affects survival outcomes. Currently, no prophylactic pharmacological or non-pharmacological interventions have received Grade I recommendations in domestic or international guidelines and expert consensuses. The compression therapy demonstrated definite preventive value in the POLAR trial. Its low cost and high tolerability confer substantial clinical applicability, earning it a Grade III recommendation in ESMO guidelines. Meanwhile, single-arm trials of acupuncture have reported a 51.2% symptom relief rate and a trend toward reduced high-grade CIPN. As non-pharmacological interventions, acupuncture and compression therapy hold complementary potential in preventing taxane-induced CIPN: compression therapy locally blocks drug exposure, while acupuncture systemically regulates neural function.However, three core challenges persist in the current research field: insufficient evidence quality for single-intervention strategies, lack of systematic evaluation of combined interventions, and the absence of risk-stratified prevention models. To address these gaps, this study aims to conduct a prospective randomized controlled trial to concurrently evaluate the preventive efficacy of compression therapy, acupuncture, and their combination for taxane-induced CIPN. The goal is to provide high-level evidence-based medicine to support the development of individualized prevention strategies.

This research is being done to determine whether a 12-week virtual Tai Chi training program, designed to improve balance and small nerve fiber function, is feasible and acceptable among cancer survivors with chemotherapy-induced peripheral neuropathy (CIPN).

Chemotherapy-induced peripheral neuropathy (CIPN) is a common complication of cancer treatment that can cause numbness, tingling, pain, balance problems, and difficulty walking. These symptoms may increase the risk of falls and reduce independence and quality of life in cancer survivors. The purpose of this study is to determine whether adding feedback-based balance training to conventional physiotherapy improves balance and walking ability in cancer patients with CIPN. Participants will be randomly assigned to one of two groups. One group will receive conventional physiotherapy along with feedback-based balance and gait training, while the other group will receive conventional physiotherapy alone. The intervention will be provided twice per week for four weeks. Balance, gait performance, neuropathy symptoms, and fear of falling will be assessed before and after the intervention using standardized clinical outcome measures. The findings of this study may help identify effective rehabilitation strategies to improve balance and mobility in cancer patients affected by chemotherapy-induced peripheral neuropathy.

This study aims to find out if taking specific dietary supplements (PEA and Scutellaria) along with therapeutic exercise can help reduce nerve pain and damage caused by chemotherapy. Many cancer patients experience nerve-related side effects from chemotherapy, which can significantly impact their quality of life. The study will observe patients who use these supplements and exercises to see if they can effectively manage and improve their nerve health and reduce pain.

Chemotherapy for colorectal cancer (CRC) is frequently complicated by chemotherapy-induced peripheral neuropathy (CIPN) and impaired sleep quality, significantly impacting patient quality of life. Low magnesium levels have been implicated in peripheral nerve dysfunction. This interventional study aims to investigate the effects of magnesium supplementation on serum magnesium concentration, CIPN severity, and sleep quality in CRC patients undergoing chemotherapy. Study Design and Methods This is a prospective, parallel-group, randomized controlled trial (RCT) utilizing a longitudinal design. Participants (CRC patients undergoing chemotherapy) will be randomly allocated to one of three groups: * Experimental Group 1: Oral magnesium (400mg) supplementation. * Experimental Group 2: Oral magnesium (400mg}) supplementation and magnesium solution foot baths. * Control Group: Standard care. Measurements will be collected using structured questionnaires and blood samples during each chemotherapy cycle. The primary outcomes will be assessed using: * Serum Magnesium Concentration * CIPN Severity: Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-neurotoxicity (FACT/GOG-Ntx) scale. * Sleep Quality: Verran and Snyder-Halpern Sleep Scale (VSH). Primary Research Questions (Hypotheses) 1. Can the magnesium intervention (oral and/or foot baths) effectively increase the serum magnesium concentration in CRC patients? 2. Can the magnesium intervention alleviate or improve the severity of CIPN? 3. Can the magnesium intervention improve the sleep quality of CRC patients during chemotherapy? The intervention groups will be compared against the control group to determine if the magnesium interventions lead to superior improvement in the measured outcomes.

The goal of this observational study is to learn about the effectiveness of closed-loop spinal cord stimulation (CL-SCS) therapy for treatment of painful chemotherapy induced peripheral neuropathy. The closed-loop SCS (CL-SCS) system stimulates the nerves in the spinal cord, measures their responses and automatically adjust the stimulation level accordingly in real time for each delivered pulse.

The first goal of this clinical trial is to assess the feasibility of transcutaneous acupoints electrical stimulation (TAES) on children with acute lymphoblastic leukemia (ALL). The second goal of this clinical trial is to evaluate the preliminary effectiveness of TAES on subject chemotherapy induced peripheral neuropathy (CIPN) symptoms severity, physical function, psychological distress, and quality of life at postintervention and at 1-, and 3-month follow-up postintervention. The main questions it aims to answer are: 1. What is the feasibility of implementing TAES for children with ALL, as measured by the eligibility rate, consent rate, randomization rate etc.? 2. Does TAES can improve CIPN symptoms severity, physical function, psychological distress, quality of life in children with ALL compared with sham control group? This proposed research is designed to conduct a two-arm RCT comparing TAES to sham TAES in children with ALL. Subjects in TAES group will receive 8 weeks TAES on four acupoints. Subjects in sham control group will follow the same protocol as the TEAS treatment but with 0 mA, 0 Hz TAES. These two groups will be provided with a leaflet containing self-help materials for CIPN.

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe side effect of several anti-cancer agents. Typical symptoms include tingling and hypoesthesia in the fingertips and/or toes, which substantially impair patients' quality of life and independence. Providing effective, evidence-based treatments for CIPN remains a major challenge in clinical practice. In a recent randomized clinical trial, our group demonstrated the effectiveness of electrotherapy in reducing both sensory and motor symptoms, as assessed by the EORTC-QLQ-CIPN20 questionnaire and CIPN grading according to CTCAE. However, these findings were based exclusively on patients' subjective self-reports (EORTC QLQ CIPN 20 and C-30). To more objectively evaluate treatment success, functional assessments that capture impairments in daily activities are needed. In this cross-sectional comparison, we will conduct comprehensive functional assessments and correlate the results with patients' subjective ratings using the EORTC-QLQ-CIPN20, QLQ-C30, and CTCAE v5.0 grading. In addition, data from matched healthy controls will be collected and compared with those of CIPN patients. The findings of this study will contribute to the development of objective measures of functional limitations caused by CIPN and provide a valuable complement to patient-reported outcome obtained through validated questionnaires.

The goal of this clinical trial is to compare the effectiveness of Transcutaneous Acupoints Electrical Stimulation (TAES) and Auricular Acupressure (AA) on subject CIPN symptoms, sensory function, motor and physical function, psychological, physical symptoms and quality of life outcomes in Children with Leukemia. The main questions it aims to answer are: 1. Does TAES and AA can improve CIPN symptoms, sensory function, motor and physical function, psychological, physical symptoms and quality of life outcomes in children with Leukemia compared with self-management control group? 2. Does TAES yield improvements in CIPN symptoms, sensory function, motor and physical function, psychological, physical symptoms and quality of life outcomes that are comparable to those achieved through AA in children with leukemia? This proposed research is designed to conduct a three-arm RCT comparing TAES, AA to usual care in children with leukemia. Subjects in TAES group will receive 8 weeks TAES on four acupoints. Subjects in AA group will receive 8 weeks on four acupoints. Subjects in self-management control group will receive usual care they will receive from the hospital. These three groups will be provided with a leaflet containing self-help materials for CIPN.

Chemotherapy induced peripheral neuropathy (CIPN) is one of the most limiting side effects of chemotherapy and often leads to adaptations in the protocol of the chemotherapy including dose reduction or even discontinuation of treatment. In general, the symptoms of CIPN are sensory, often distributed in a "stocking and glove" manner, and include pain, tingling, and numbness. CIPN has a marked negative influence on quality of life of patients and their families. It may result in serious limitations in daily functioning and affect the enjoyment, social relationships, and ability to perform work. Current management of CIPN (i.e. prevention and treatment) includes dose reduction or delay of chemotherapy cycles and treatment discontinuation. Unfortunately, this reduces the chance of an effective cancer treatment. Current guidelines of the American Society of Clinical Oncology (ASCO) on the Prevention and Management of Chemotherapy-Induced Peripheral Neuropathy do not conclusively recommend any agent for the prevention of CIPN. Due to the scarcity of drugs that are effective for preventing and treating CIPN, the distress of patients who suffer from CIPN, and the major societal and economic costs, new approaches and effective treatment strategies are required. The proposed trial is a parallel, double blind, placebo controlled, randomised, phase III superiority trial, aiming to determine whether treatment with SMP prevents incidence of or reduces the severity symptoms of paclitaxel-induced peripheral neuropathy, as compared to placebo.

To evaluate the preventive efficacy of a simple surgical glove compression technique in reducing the incidence and severity of Chemotherapy Induced Peripheral Neuropathy among patients receiving chemotherapy.

This study is a randomized, double-blind, multicenter, placebo-controlled phase III clinical trial, aiming to evaluate the efficacy and safety of GM1 in preventing chemotherapy-induced peripheral neuropathy in breast cancer patients treated with Albumin-paclitaxel chemotherapy regimen.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and common side effect of neurotoxic cancer treatment. The most frequent symptoms include sensory disturbances and weakness in the hands and/or feet. CIPN can interfere with both daily activities and cancer treatment itself. Although there is proof of concept for physical activity as a preventive measure for CIPN, physical activity is currently not included in the international evidence-based guideline for the prevention of CIPN due to the need of larger sample-sized definitive studies. The aim of this project is, on the one hand, to investigate the preventive effect of an exercise program based on international physical activity guidelines on CIPN symptoms in patients with breast or colorectal cancer undergoing taxane- or platinum-based chemotherapy. On the other hand, the study will also explore how patients and healthcare professionals experience the implementation of physical activity during this phase of therapy. A prospective randomized controlled trial will be conducted, with CIPN symptoms as the primary outcome measure.

This study is being done to evaluate the potential benefits of using electroacupuncture to reduce the severity of chemotherapy-induced peripheral neuropathy for patients with peripheral neuropathy after chemotherapy.

A Phase I open label, dose-escalation and expansion study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of AK135 for the treatment of chemotherapy-induced peripheral neuropathy in patients with malignant tumor

Chemotherapy-induced peripheral neuropathy (CIPN) is a common and debilitating side effect of chemotherapy (CT), often requiring dose reductions or treatment interruptions, which can compromise efficacy of the planned CT (limiting its efficacy). Additionally, CIPN usually decreases patients' quality of life. Unfortunately, effective treatments for CIPN are limited. Emerging evidence suggests potential benefits of rectal ozone therapy and points to a possible role of the gut microbiome in CIPN development and treatment response. This observational study, ancillary to the randomized clinical trial (RCT) OzoParQT (NCT06706544), investigates the relationship between gut microbiome composition and CIPN severity in patients receiving rectal ozone therapy. Primary Objectives: To evaluate if gut microbiome profiles differ between patients: 1. with and without symptomatic improvement of CIPN. 2. receiving rectal ozone therapy and those receiving placebo. Secondary Objectives: To evaluate the relationship between gut microbiome composition and: 1. Health-related quality of life, 2. Anxiety and depression, 3. Biochemical markers of oxidative stress and inflammation. Main Trial Endpoints. Changes from baseline at the end of ozone therapy (week 16) in: * Gut microbiome profile * Patient-reported numbness and tingling * Neuropathy severity (QLQ-CIPN20 scale) * Paresthesia toxicity grade (CTCAE v.5.0) Secondary Trial Endpoints. Changes from baseline at the end of ozone therapy (week 16) in: * Patient-reported quality of life (EQ-5D-5L questionnaire) * Quality of life (QLQ-C30 questionnaire) * Anxiety and depression levels (HADS questionnaire) * Biochemical markers of oxidative stress * Biochemical markers of inflammation Trial Design: This observational study will analyze data from patients enrolled in the randomized, triple-blind, placebo-controlled OzoParQT clinical trial (NCT06706544). Trial Population in the OzoParQT trial (NCT06706544): Adults (≥18 years) with any tumor type, experiencing CIPN-related paresthesias (numbness and/or tingling), with a toxicity grade ≥ 2 according to the Common Terminology Criteria for Adverse Events (CTCAE v.5.0) for ≥ 3 months. Intervention in the OzoParQT trial (NCT06706544). All patients will receive standard care for their CIPN symptoms plus 40 sessions of rectal insufflation of an O3/O2 gas mixture over 16 weeks: * Ozone group: O3/O2 concentration increasing from 10 to 30 µg/mL * Control-placebo group: O2 only (0 µg/mL O3) Study Duration: Each patient will participate in this study (OzoParQTmicrob) for 16 weeks, concurrent with the ozone therapy intervention. The total planned project duration is 60 months.