Evaluation of the Efficacy of Donepezil in the Treatment of Oxaliplatin-induced Peripheral Neuropathy: Proof of Concept Study
The use of oxaliplatin in the treatment of colorectal or pancreas cancer induces (>75% of patients) severe sensorimotor neuropathy decreasing the quality of life of cancer survivors. Today, no treatment remains univocal for these peripheral neuropathies. But preclinical works have demonstrated that donepezil (acetylcholinesterase inhibitor use for Alzheimer's disease) was able to prevent and treat neuropathic symptoms in oxaliplatin-treated rats. Present study aims to assess the therapeutic efficacy of donepezil on oxaliplatin-induced peripheral neuropathy (OIPN) in cancer survivors. Bibliographic data suggests an antineuropathic effect of donepezil in human and animal models. In clinic, a study have shown in healthy volunteers that donepezil (associated with gabapentin) reduced the pain threshold (better than gabapentin alone) caused by stimulation of the sural nerve, without severe adverse effect. Similarly, two studies in patients with neuropathic pain demonstrated that donepezil increases analgesic effect of gabapentin. Finally, a case report demonstrated an analgesic effect of donepezil in painful Alzheimer's disease patients. In animals, several studies demonstrated that donepezil induces analgesic and neuroprotective effects. Recently, a preclinical study demonstrated that donepezil induced antineuropathic effect in diabetic mice with neuropathic pain. Research unit INSERM U1107 (partner of the DONEPEZOX study) demonstrated the antineuropathic effects of donepezil in several animal models of chemotherapy-induced peripheral neuropathies, and very recently, a study have confirmed these results with oxaliplatin and cisplatin. These clinical and preclinical data have thus highlighted the potential beneficial effect of donepezil on neuropathic symptoms, without any significant adverse effects. Therefore the hypothesis is that the use of donepezil could reduce the symptoms of OIPN, limit the decrease in quality of life and the appearance of comorbidities (anxiety/depression) in cancer survivors. For this purpose, the investigators propose here a proof of concept, multicentre, phase II, randomised, double-blind, placebo-controlled clinical study. The primary objective will be the curative efficacy of donepezil on the severity of OIPN in patients who have completed oxaliplatin-based chemotherapy for the treatment of colorectal or pancreas cancer and have peripheral neuropathy of grade ≥2. This will be assessed using the EORTC QLQ-CIPN20 sensory scale. Our methodological choice to use the QLQ-CIPN20 as the primary endpoint will allow us to more accurately (and in a standardized manner) characterize neuropathic symptoms and assess the therapeutic effect of donepezil on these symptoms. In addition, as secondary objectives, we will study the effect of donepezil on neuropathic pain, the intensity of neuropathic symptoms, health-related quality of life, and the tolerance of donepezil. The 80 patients required will be randomized (1:1) to receive either placebo or donepezil (5 mg daily for 4 weeks and then 10 mg daily for 12 weeks as a single dose and according to tolerance and efficacy). Patients will be followed for 1 month after the end of treatment to assess the OIPN. As a proof of concept study, responder rate will be assessed only for Donepezil arm (primary objective) and compared between each treatment arm (secondary objective) after a minimum of 12 weeks of treatment. A responder will be defined as a patient with a decrease of neuropathic grade according to CIPN20 sensory score compraed to baseline.
NCT05254639 — Supportive Care
Status: Completed
http://inclinicaltrials.com/supportive-care/NCT05254639/
Prevalence of Peripheral Neuropathy Among Patients With Auditory Neuropathy
Auditory neuropathy/ dys-synchrony/ peri-synaptic audiopathy (AN) are terms used to describe a specific hearing disorder with a disturbed auditory neural response in presence of normal cochlear function. Initially reported as early as the 1970s by ( Hinchcliffe et al) after observation of the patients with normal hearing thresholds, who had difficulty to detect the sounds especially in presence of background noise . Auditory Neuropathy is characterized by five integral features that distinguish it from other types of hearing loss. These are: Variable audiometric results anywhere from normal hearing to Sensorineural hearing loss of any degree up to profound hearing loss showing unusual audiometric pattern , Preserved outer hair cells (OHCs) responses such as otoacoustic emissions (OAEs) and/or cochlear microphonics (CM) , Altered neural processing such abnormal auditory brainstem responses (ABRs) with a reduced or absent wave V , Poor speech perception with poor speech recognition score that seems out of proportion compared to their pure-tone detection thresholds. , absent stapedial reflexes to the ipsilateral and contralateral tone at a 110-dB hearing level . In 2008 it was found that AN does not represent a single disease entity but it is a heterogeneous disease category with a wide range of hearing loss types ,etiologies , age and clinical manifestations hence the adoption of the term auditory neuropathy spectrum disorder (ANSD) by an International Newborn Hearing Screening Conference held in Italy following a comprehensive study of newborn hearing test results. The prevalence of ANSD is variable in published studies from (0.23 to 15%) among hearing impaired individuals . Regarding the underlying etiological factors, auditory neuropathy can be congenital or acquired . AN without the involvement of the neurological system has been termed as primary auditory neuropathy (PAN). Peripheral neuropathy is not a constant finding in all patients with this hearing disorder , AN may occur in the afferent pathway of acoustic nerve, probably accompanied by the pathological changes of efferent nerve in the olivocochlear system inside the brainstem Our study is conducted to detect the prevalence of peripheral neuropathy among patients with auditory neuropathy spectrum disorder .
NCT06041360 — Auditory Neuropathy Spectrum Disorder,, Peripheral Neuropathy
Status: Recruiting
http://inclinicaltrials.com/auditory-neuropathy-spectrum-disorder-peripheral-neuropathy/NCT06041360/
A Randomized Placebo-controlled Trial of Glutamine to Reduce the Signs and Symptoms of Peripheral Neuropathy in Breast Cancer Patients With a Mild Peripheral Neuropathy Receiving Paclitaxel Chemotherapy
Patients with breast cancer receiving paclitaxel chemotherapy who have mild symptoms of peripheral neuropathy will receive glutamine or placebo to try and improve symptoms.
NCT00195013 — Breast Cancer
Status: Completed
http://inclinicaltrials.com/breast-cancer/NCT00195013/
Chemotherapy Induced Peripheral Neuropathy (CIPN): A Pilot Study of Intraneural Facilitation for Managing Chemotherapy-Induced Peripheral Neuropathy
Chemotherapy induced peripheral neuropathy (CIPN) is a common side effect of many forms of chemotherapy having a negative impact on the quality of life for cancer survivors due to numbness, decreased sensation, pain (of various intensities in the extremities), gait/balance problems, and difficulty with fine motor skills of the hands and fingers.To date, there are no preventive modalities to mitigate CIPN development.When CIPN becomes intolerable, optimal doses of chemotherapy have to be reduced or discontinued, which may affect a patient's overall survival. Intraneural facilitation (INF) is a technique developed by physical therapists at Loma Linda University after careful study of the structure, pathophysiology and biomechanics of peripheral nerves. The focus of INF is restoration of circulation to an ischemic nerve. INF has been offered to subjects receiving treatment at LLUCC with anecdotal success. The purpose of this study is to evaluate INF as a treatment modality under the rigor of scientific inquiry to determine its effectiveness as a viable treatment option for breast cancer patients with CIPN.
NCT03272919 — Chemotherapy-induced Peripheral Neuropathy
Status: Completed
http://inclinicaltrials.com/chemotherapy-induced-peripheral-neuropathy/NCT03272919/
Evaluation of Trimetazidine in Alleviating Paclitaxel-Induced Peripheral Neuropathy in Breast Cancer Patients
This proof-of-concept study evaluated the effect of Trimetazidine on the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer.
NCT06459193 — Peripheral Neuropathy Due to Chemotherapy
Status: Not yet recruiting
http://inclinicaltrials.com/peripheral-neuropathy-due-to-chemotherapy/NCT06459193/
Clinical Biomarker of Paclitaxel-induced Peripheral Neuropathy
Investigation of which patients treated with paclitaxel have an increased risk of developing peripheral neuropathy.
NCT06430814 — Chemotherapy-induced Peripheral Neuropathy
Status: Not yet recruiting
http://inclinicaltrials.com/chemotherapy-induced-peripheral-neuropathy/NCT06430814/
A Study on the Efficacy and Safety of HILOTERM® Device for the Prevention of Chemotherapy-induced Peripheral Neuropathy in Early Breast Cancer Patients
Taxol is a very effective drug in breast cancer, but it can cause peripheral neuropathy (PN). This toxicity is often dose-limiting. Symptoms of PN usually improve after taxol discontinuation, but >80% of affected women experience symptoms 1-3 years after treatment stop. The intensity, the duration and the type of symptoms related to PN are very different and they can strongly interfere with patients' quality of life. The application of cold to the hands and feet seems to be able to reduce the incidence of PN. Hilotherm® is a machine that allows to cool hands and feet. The aim of this study is to verify whether the use of Hilotherm® is able to reduce the incidence of moderate and severe PN and to evaluate the tolerability of Hilotherm® and its impact on quality of life.
NCT06422949 — Breast Cancer
Status: Not yet recruiting
http://inclinicaltrials.com/breast-cancer/NCT06422949/
EX-CIPN: An Exercise-based Rehabilitation Intervention to Treat Persistent Chemotherapy-Induced Peripheral Neuropathy (CIPN)
The goal of this clinical trial is to learn if the EX-CIPN exercise-based intervention is feasible, acceptable, and safe in participants with persistent chemotherapy-induced peripheral neuropathy (CIPN). It will also give insight on the effectiveness of the exercise intervention in treating CIPN symptoms. The main questions it aims to answer are: - Is EX-CIPN safe, acceptable, and feasible in cancer survivors experiencing persistent CIPN? - Are the study design and methods feasible (recruitment and retention rates, feasibility of data collection and procedures)? Researchers will provide all participants with the exercise-based intervention. Participants will: - Complete assessments at baseline, immediately post-intervention, and 3-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
NCT06405542 — Chemotherapy-induced Peripheral Neuropathy
Status: Recruiting
http://inclinicaltrials.com/chemotherapy-induced-peripheral-neuropathy/NCT06405542/
a Prospective, Randomized, Open-Label, Clinical Trial Study Comparing the Efficacy and Safety for Needle-Free Subcutaneous Injector and Conventional Intramuscular Injection of Mecobalamin in Diabetes Peripheral Neuropathy
The evaluation for efficacy and safety of needle-free subcutaneous injector and conventional intramuscular injection of mecobalamin for diabetic neuropathy.
NCT06400888 — Diabetic Peripheral Neuropathy
Status: Not yet recruiting
http://inclinicaltrials.com/diabetic-peripheral-neuropathy/NCT06400888/
Understanding and Preventing Cortical Mechanisms of Chemotherapy-induced Peripheral Neuropathy
Cohort 1: To track the onset and progression of a condition called chemotherapy-induced peripheral neuropathy (CIPN). Cohort 2: To track the onset and progression of a condition called chemotherapy-induced peripheral neuropathy (CIPN) and to test a certain type of experimental neuromodulation (stimulation of the brain) with a device called a closed-loop brain-computer interface (clBCI) to see if can help to prevent pain due to CIPN.
NCT06389721 — Chemotherapy-induced Peripheral Neuropathy
Status: Not yet recruiting
http://inclinicaltrials.com/chemotherapy-induced-peripheral-neuropathy/NCT06389721/