Nervous System Diseases

All Conditions

Behaviors and Mental Disorders

Peripheral Nervous System Diseases

Neuromuscular Diseases

Quality of Life

Individuals with a history of non CNS cancer with cancer treatment induced peripheral neuropathy symptoms.

Age and gender matched individuals without peripheral neuropathy symptoms.

Priya Karakkattil

Priya Karakkattil, PhD

Asha Vas, PhD

The purpose of this research is to examine the impact of peripheral neuropathy on fall risk and quality of life in people who had cancer. Specifically, we are interested to find out if you have any difficulty with thinking, feeling, balancing, or moving around that will contribute to risk for falls or quality of life. We are also interested to see if you have any difficulty with doing two activities at the same time, such as walking and texting.

Cancer related cognitive impairment (CRCI) is a common side effect of treatment of cancer during and after chemotherapy and is seen in patients with non-central nervous system( non-CNS) cancer (Lange, Joly, et al., 2019; Pendergrass et al., 2018). Though common after chemotherapy, other treatments such as hormone therapies and targeted therapies can also cause cognitive deficits.(Lange, Joly, et al., 2019). The self-reported prevalence of cognitive complains in cancer survivors was 75% in a large web based study with non CNS cancers (Lange, Licaj, et al., 2019). The clinical presentation of these cognitive impairments include memory deficits, difficulty with learning attention, concentration, reasoning, processing speed, executive functions and visuospatial skills(Mounier et al., 2020). Therefore the cognitive impairment can have a negative impact on quality of life, daily functioning and ability to work in patients with cancer while undergoing treatment and while in remission(Pendergrass et al., 2018).

Acquired Peripheral Neuropathy (APN) is another common side effect of treatment for cancer. While majority of the peripheral neuropathy symptoms are due to neurotoxic chemotherapy agents resulting in chemotherapy-induced peripheral neuropathy (CIPN), neuropathy symptoms can also occur as paraneoplastic, immune-mediated, or neoplastic neuropathies.(Staff et al., 2017). The reported prevalence of CIPN is 68% within first month after chemotherapy and continued to be present in 47% of the survivors even 6 years later(Autissier, 2019). The clinical presentation of the CIPN includes numbness, tingling, or burning, neuropathic pain, decrease of muscle tone and coordination, and loss of balance(Autissier, 2019). The symptoms tends to begin distally in the fingers and toes and moves proximally through the extremities (Autissier, 2019). CIPN is typically associated with treatment using platinum based drugs, taxanes, epothilones, vinca alkaloids, bortezomib and thalidomide (Hu et al., 2019).

Individuals with CIPN are significantly more likely to suffer falls and fall related injuries (Autissier, 2019). In breast cancer survivors with neuropathy, 40.9% experienced falls on both flat surfaces and non-flat surfaces during upright activities(Komatsu et al., 2019). Gait is a complex functional activity that requires the integration of the musculoskeletal, sensory, neurological, and cognitive systems(Fritz \& Lusardi, 2009). Significant gait variability in step width and step length with forward walking has been reported in cancer survivors with peripheral neuropathy compared to healthy controls(Hsieh et al., 2019). However, normal daily walking does not include just walking in a forward direction, but rather it involves walking in different directions such as walking backwards to sit in a chair. Although gait variability has been reported with forward walking, the gait variability while walking backwards in patients with cancer with APN has not been investigated previously.

Cognitive impairment has been strongly associated with decreased performance in dual task abilities and higher number of falls in older adults (Allali et al., 2017; Li \& Harmer, 2020). Performing concurrent tasks such as walking and talking or walking and texting is a normal aspect of life. Concurrent performance of two tasks with distinct motor and cognitive demands has been associated with increased fall risk in older adults(Belur et al., 2020). Ability to do such dual task (DT) has shown to be declined in persons with cognitive and motor impairments(Abou et al., 2022; Bryk et al., 2023; Ozkul et al., 2021). Ability to perform DT has been also reported to be affected in persons with diabetic peripheral neuropathy (Parveen \& Noohu, 2023). There is only one reported study that evaluated the cognitive and sensory deficits associated with orbital stability in gait on treadmill during single and dual task in cancer survivors with and without peripheral neuropathy(Monfort et al., 2019). However, walking on the treadmill at fixed speed does not translate to the real-world adaptations on overground walking in different directions with the added challenge of a cognitive task. Though cognitive and peripheral neuropathy symptoms are reported in patients with non- CNS cancers who are undergoing treatment and while in remission, ability to perform dual task with forward and backward walking has not been assessed in this population and not compared with an age and gender matched control without peripheral neuropathy. Additionally, it is important to investigate what cognitive, motor and sensory impairments can predict fall risk and decreased quality of life in this population compared to an age and gender matched control.

The purpose of this proposed exploratory pilot study is to evaluate the dual task cost of variable walking in individuals diagnosed with cancer treatment induced peripheral neuropathy compared to age and gender matched individuals without peripheral neuropathy. backward walking on an over ground computerized mat. A secondary purpose will be to identify what type of cognitive, motor and sensory impairments can correlate quality of life in individuals diagnosed with cancer treatment induced peripheral neuropathy and can predict fall risk in this population compared to compared to age and gender.

Fall Risk and Quality of Life: in Individuals With Cancer Treatment Related Peripheral Neuropathy.

Fall Risk and Quality of Life: Influence of Dual Task Performance, Cognition, and Sensorimotor Variables in Individuals With Cancer Treatment Related Peripheral Neuropathy.

Fall risk will be assessed using the Timed Up and Go (TUG)-Test.(Blackwood \& Rybicki, 2021) For the TUG, the participant will be asked to stand up from a chair, walk 3 m and touch a line on the floor, walk back to the chair and sit down. Timing of the test will begin when the tester gives the command "go" and will be stopped when the participant made contact with the chair as they sat down.

Participants in the cancer related peripheral neuropathy group will complete the Functional Assessment of Cancer Therapy- General (FACT-G ) to assess self-reported quality of life.

TMT test assesses attention, psychomotor, and higher-level cognitive function and has been recommended to be used to in cancer population

Single task assessment of working memory will be assessed by randomly picking one of the following tests (serial sevens (7s), spelling words backwards or recite months backwards) for 30 seconds in seated position.

Visual-attention cognitive tasks will be tested by randomly selecting one of the following texting activity for 30 seconds (texting animal names, cities, or colors on a smart phone) in a seated position. (Belur et al., 2020)

Protective sensation in the upper and lower extremities will be measured using the Semmes-Weinstein monofilament.

Grip strength will be assessed using a Jamar handheld dynamometer.

Muscle strength testing of the ankle dorsiflexors, knee flexors, knee extensors, hip flexors, hip extensors and hip abductors using a handheld dynamometer using a make test.

Dynamic balance and coordination will be assessed using the Four-Square Step Test (FSST).

For the single task gait component, we will utilize the Zeno© Electronic Walkway for assessing walking in both forward and backward directions using self-selected speed. Participants will commence/continue walking two feet prior to and after contacting the electronic walkway to account for acceleration and deceleration.

Participants will complete three trials of walking forward and three trials of walking backward with simultaneous execution of a randomly selected working memory task (serial sevens (7s), spelling words backwards or recite months backwards)

Participants will complete three trials of walking forward and three trials of walking backward with simultaneous execution of a randomly selected visual-attention cognitive task (texting animal names, cities, or colors on a smart phone)

Texas Woman's University

Assistant Professor

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Respiratory System Agents

Amino Acids

Paclitaxel

Albumin-Bound Paclitaxel

Acetylcysteine

N-monoacetylcystine

Tubulin Modulators

Antimitotic Agents

Antiviral Agents

Expectorants

Antioxidants

Protective Agents

Antidotes

Cysteine

they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only

they will receive paclitaxel 80 mg/m2 once per week for 12 weeks and high dose N-acetylcysteine (1200 mg twice daily) for the paclitaxel treatment period

they will receive paclitaxel 80 mg/m2 once per week for 12 weeks and low dose N-acetylcysteine (600mg twice daily) for the paclitaxel treatment period.

low dose N-acetylcysteine

high dose N-acetylcysteine

Hadeer G Khalefa, master

The purpose of the study is to evaluate the effect of N-acetyl cysteine in combination with paclitaxel on the clinical outcomes of patients with peripheral neuropathy, paclitaxel-induced peripheral neuropathy affect quality of life in cancer patients.

new therapeutic approches such as the antioxidant N-acetyl cysteine, showed to has neuroprotective effect, the aim of the study is to evaluate the effect of N- acetylcysteine(NAC) administration in the prevention of paclitaxel-Induced peripheral neuropathy.

Paclitaxel is a first-line chemotherapeutic treatment of solid tumors. Neuronal damage also seems to have a major role in paclitaxel-induced neuropathic pain, paclitaxel contributes to ROS formation (superoxide, hydroxyl radical, nitric oxide and hydrogen peroxide) in neuronal mitochondria that are involved in nerve injury-induced.

N-acetylcysteine (NAC) is a cysteine pro-drug and glutathione (GSH) precursor which is a protective agent and detoxifies and scavenges reactive oxygen species (ROS), which seems to help normalize the oxidative status.

It has been reported that high dose of N-acetylcysteine shown to Prevent retrograde motor neuron death after neonatal peripheral nerve injury and significantly increases motor neuron survival, which may improve functional outcomes after obstetrical brachial plexus injury in rats.

Also, it has been reported that NAC significantly inhibited CCI-induced microglia activation but elicited no notable effects on astrocytes. These results demonstrate an effective and safe approach that has been used clinically to alleviate neuropathic pain via the powerful inhibition of the activation of MMPs in rats.

N-acetylcysteine has been shown to have neuroprotective effects against oxaliplatin-based adjuvant chemotherapy in colon cancer patients with Oral administration of N-acetylcysteine1,200 mg) was given one and a half hours before each oxaliplatin administration.

N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Evaluation of The Effect of N-AcetylCysteine in The Prevention of Paclitaxel-Induced Peripheral Neuropathy in Cancer Patients

measures quality of life related to signs and symptoms of paclitaxel induced peripheral neuropathy

measuring serum level of nerve growth factor using ELISA KIT

measuring serum level of maliomaldehyde using spectrophometric kit

Number of patients reported neuropathy from paclitaxel

severity of paclitaxel induced peripheral neuropathy using NCI-CTCAE criteria

any adverse/ side effect will be evaluated

severity of chemotherapy induced-peripheral neuropathy using modified total neuropathy score ,Each neuropathy item is scored by a physician on a 0-4 scale the scores are summed to obtain a total score, modified total neuropathy score score ranges from 0-24 with higher total scores indicate more severe neuropathy.

Nasser Institute For Research and Treatment

Ain Shams University

pharmacist

Neoplasms

Skin and Connective Tissue Diseases

Breast Neoplasms

The selection of acupuncture points is based on Traditional Chinese Medicine (Wen 2011) and on previous studies (Jeong, 2018; Bao,2018), selected as main points: bilateral "baxie", SJ5, "bafeng", KID3 and ST36. Modifications or additional secondary points may be indicated according to clinical judgment throughout treatment.

Patients will receive needling at non-acupuncture points with superficial needling without manipulation to obtain "de qi", located near the real points in the hands and feet.

The selection of acupuncture points is based on Traditional Chinese Medicine (Wen, 2011) and on previous studies (Jeong,2018; Bao,2018), selected as main points: bilateral "baxie", SJ5, "bafeng", KID3 and ST36. Modifications or additional secondary points may be indicated according to clinical judgment throughout treatment. The needles will be inserted at a depth of 10 - 15 mm, being gently manipulated to obtain "de qi" sensation. The needles will be left for 20 - 25 minutes. There will be once a week acupuncture treatment, for 8 consecutive weeks. The acupuncture needles will be sterile, disposable stainless steel needles size 0.20 x 30 mm, of Korean brand Dong Bang, Chungcheongnam-do.

True acupuncture

Patients will receive needling at non-acupuncture points with superficial needling without manipulation to obtain "de qi", located near the real points in the hands and feet. The needles will also be left for 20 - 25 minutes. There will be once a week acupuncture treatment, for 8 consecutive weeks. There will be once a week acupuncture treatment, for 8 consecutive weeks. The acupuncture needles will be sterile, disposable stainless steel needles size 0.20 x 30 mm, of Korean brand Dong Bang, Chungcheongnam-do.

Sham acupuncture

Lin I Ter, MD

The present study aims to evaluate the effectiveness of acupuncture in the treatment of chemotherapy drug paclitaxel induced peripheral neuropathy in patients with early stage breast cancer

Patients with early stage breast cancer (stages I,II,III) who received paclitaxel in neoadjuvant or adjuvant chemotherapy protocol and developed peripheral neuropathy will be randomized to receive true acupuncture (intervention group) vs sham acupuncture (control), once a week, for 8 weeks. The primary outcome is improvement of the symptoms by Neuropathic Pain Symptom Inventory (NPSI) scale (Bouhassira,2004). The secondary outcomes are improvements on Visual analog scale (VAS) and Quality of life by FACT-taxane (Cella, 2003) questionnaire. These scales will be assessed in the Screening visit (baseline), week 4, week 6, week 8 and week 12. The study has duration of 12 weeks.

Acupuncture for Peripheral Neuropathy Induced by Paclitaxel in Early Stage Breast Cancer

Acupuncture for Treatment of Peripheral Neuropathy Induced by Neoadjuvant or Adjuvant Paclitaxel in Early Stage Breast Cancer: a Sham Controlled, Randomized Study

Neuropathic Pain Symptom Inventory (NPSI) scale. This tool included 12 items in total: 10 are differential symptoms descriptors and 2 items evaluate spontaneous and paroxysmal spontaneous pain. The verbal numeric scale from zero (no pain) to 10 (worst imaginable pain). Total pain intensity score may be calculated by the sum of 10 descriptors.

Visual analog scale (VAS). The pain VAS is a unidimensional measure of pain intensity. It is a continuous scale comprised of a horizontal (HVAS) or vertical (VVAS) line, usually 10 centimeters (100 mm) in length. For pain intensity, the scale is most commonly anchored by "no pain" (score of 0) and "pain as bad as it could be" or "worst imaginable pain" (score of 100 \[100-mm scale\]).

FACT-taxane questionnaire. It is a self-report instrument that was developed to measure the health-related Quality of life of patients receiving taxane-containing chemotherapy. This scale has 16 items, including an 11-item neurotoxicity subscale and five additional taxane-specific questions related to the effects of arthralgia, myalgia, and skin changes. The total score is calculated as the sum of the un-weighted subscale score.

Instituto Brasileiro de Controle do Cancer

Anti-Arrhythmia Agents

Antihypertensive Agents

Vasoconstrictor Agents

Losartan

Angiotensin II

Giapreza

Angiotensinogen

Angiotensin II Type 1 Receptor Blockers

Angiotensin Receptor Antagonists

These patients will receive standard-of-care management for chemotherapy-induced nausea and vomiting

These patients will receive standard-of-care management for chemotherapy-induced nausea and vomiting plus losartan 100mg

Using losartan to prevent paclitaxel-induced peripheral neuropathy

Alaa Mahmoud Ahmed Shawqy, Bachelor's

Farida Ali

Paclitaxel-induced peripheral neuropathy (PIPN) is one of the most dose-limiting side effects; it causes patients discomfort and pain and sometimes causes the termination of the chemotherapy cycles, leading to treatment failure. A lot of interventions have been tried to prevent PIPN, ensure complete administration of the chemotherapy cycles, and increase the survival rate. One of the promising interventions in the prevention of PIPN is Losartan. Losartan is an angiotensin receptor blocker (ARBs) and is used to treat hypertensive patients. There is strong evidence from different preclinical studies and retrospective cohort studies that Losartan has a neuroprotective effect.

The purpose of our study is to investigate the efficacy of Losartan in the prevention of peripheral neuropathy associated with Paclitaxel treatment in Breast Cancer patients.

Prevention of Paclitaxel-induced Peripheral Neuropathy in Breast Cancer Patients

Efficacy of Losartan in the Prevention of Paclitaxel-induced Peripheral Neuropathy in Breast Cancer Patients.

Incidence of Development of paclitaxel-induced peripheral neuropathy

Neuropathy grade according to NCI Common Terminology Criteria for Adverse Events

Patient quality of life will be assessed by Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX)

Level of Nerve growth factor (NGF) in Serum

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Fall Risk and Quality of Life: in Individuals With Cancer Treatment Related Peripheral Neuropathy.	NCT06313359	Peripheral Neur...		18 Years -	Texas Woman's University
Fall Risk and Quality of Life: in Individuals With Cancer Treatment Related Peripheral Neuropathy.	NCT06313359	Peripheral Neur...		18 Years -	Texas Woman's University
N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients	NCT03492047	Peripheral Neur...	low dose N-acet... high dose N-ace... Paclitaxel	18 Years - 85 Years	Ain Shams University
Fall Risk and Quality of Life: in Individuals With Cancer Treatment Related Peripheral Neuropathy.	NCT06313359	Peripheral Neur...		18 Years -	Texas Woman's University
Acupuncture for Peripheral Neuropathy Induced by Paclitaxel in Early Stage Breast Cancer	NCT04461977	Peripheral Neur...	True acupunctur... Sham acupunctur...	18 Years -	Instituto Brasileiro de Controle do Cancer
Prevention of Paclitaxel-induced Peripheral Neuropathy in Breast Cancer Patients	NCT06135493	Peripheral Neur...	Losartan	18 Years -	Future University in Egypt

Spots Global Cancer Trial Database for peripheral neuropathy due to chemotherapy