N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

Sponsor

Ain Shams University (Other)

Overall Status

Completed

CT.gov ID

NCT03492047

Collaborator

Nasser Institute For Research and Treatment (Other)

Enrollment

Location

Arms

14.9

Actual Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Peripheral Neuropathy Due to Chemotherapy	Dietary Supplement: low dose N-acetylcysteine Dietary Supplement: high dose N-acetylcysteine Drug: Paclitaxel	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

75 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 1, 2018

Actual Primary Completion Date :

Apr 1, 2019

Actual Study Completion Date :

Jun 30, 2019

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: control they will receive paclitaxel 80 mg/m2 once per week for 12 weeks only	Drug: Paclitaxel Paclitaxel 80mg /m2 IV
Experimental: high dose N-acetyl cysteine 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	Dietary Supplement: high dose N-acetylcysteine N-acetylcysteine 1200mg twice daily Drug: Paclitaxel Paclitaxel 80mg /m2 IV
Experimental: low dose N-acetyl cysteine 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.	Dietary Supplement: low dose N-acetylcysteine N-acetylcysteine 600mg twice daily Drug: Paclitaxel Paclitaxel 80mg /m2 IV

Arm

Intervention/Treatment

Active Comparator: control

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

Drug: Paclitaxel

Paclitaxel 80mg /m2 IV

Experimental: high dose N-acetyl cysteine

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

Dietary Supplement: high dose N-acetylcysteine

N-acetylcysteine 1200mg twice daily

Drug: Paclitaxel

Paclitaxel 80mg /m2 IV

Experimental: low dose N-acetyl cysteine

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.

Dietary Supplement: low dose N-acetylcysteine

N-acetylcysteine 600mg twice daily

Drug: Paclitaxel

Paclitaxel 80mg /m2 IV

Outcome Measures

Primary Outcome Measures

Incidence of chemotherapy induced-peripheral neuropathy [up to 12 week]
Number of patients reported neuropathy from paclitaxel

Secondary Outcome Measures

severity of chemotherapy induced-peripheral neuropathy [at baseline and before each cycle up to 12 week]
severity of paclitaxel induced peripheral neuropathy using NCI-CTCAE criteria
Adverse effects [at baseline and each cycle up to 12 week]
any adverse/ side effect will be evaluated
severity of chemotherapy induced-peripheral neuropathy [at baseline, at the end of 6 cycle and at the end of 12 cycles]
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.

Other Outcome Measures

the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale [weekly up to 12 week]
measures quality of life related to signs and symptoms of paclitaxel induced peripheral neuropathy
serum nerve growth factor [at baseline and after 12 week]
measuring serum level of nerve growth factor using ELISA KIT
serum malionaldehyde [at baseline and after 12 week]
measuring serum level of maliomaldehyde using spectrophometric kit

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Adult patients (>18 years old).
Breast cancer patients who will receive adjuvant weekly paclitaxel for 12 cycles.
ECOG performance status 0-2
Adequate bone marrow function (white blood count ≥4,000/mm3, platelet count ≥100,000/mm3), liver function (serum total bilirubin <1.5 mg/dl), renal function (creatinine <1.5 mg/dl).

Exclusion Criteria:

Patients who have any of the following:

Clinical neuropathy.
Diabetes mellitus.

Patients receiving vitamin B1, B6, B12,or other vitamin supplemental therapy.
Patients receiving antidepressants, opioids, adjuvant analgesic agents (eg, anticonvulsants, clonazepam, or mexiletine), topical analgesics, and amifostine.
Hypersensitivity to NAC.