N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients

NCT ID: NCT03492047

Last Updated: 2020-02-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-04-01
• Study Completion Date: 2019-06-30

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.

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.

Conditions

Peripheral Neuropathy Due to Chemotherapy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

control

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

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

Paclitaxel 80mg /m2 IV

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

Group Type: EXPERIMENTAL

high dose N-acetylcysteine

Intervention Type: DIETARY_SUPPLEMENT

N-acetylcysteine 1200mg twice daily

Paclitaxel

Intervention Type: DRUG

Paclitaxel 80mg /m2 IV

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.

Group Type: EXPERIMENTAL

low dose N-acetylcysteine

Intervention Type: DIETARY_SUPPLEMENT

N-acetylcysteine 600mg twice daily

Paclitaxel

Intervention Type: DRUG

Paclitaxel 80mg /m2 IV

Interventions

low dose N-acetylcysteine

N-acetylcysteine 600mg twice daily

Intervention Type: DIETARY_SUPPLEMENT

high dose N-acetylcysteine

N-acetylcysteine 1200mg twice daily

Intervention Type: DIETARY_SUPPLEMENT

Paclitaxel

Paclitaxel 80mg /m2 IV

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

1. Adult patients (>18 years old).

2. Breast cancer patients who will receive adjuvant weekly paclitaxel for 12 cycles.

3. ECOG performance status 0-2

4. 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

1. Patients who have any of the following:

• Clinical neuropathy.
• Diabetes mellitus.

2. Patients receiving vitamin B1, B6, B12,or other vitamin supplemental therapy.

3. Patients receiving antidepressants, opioids, adjuvant analgesic agents (eg, anticonvulsants, clonazepam, or mexiletine), topical analgesics, and amifostine.

4. Hypersensitivity to NAC.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Nasser Institute For Research and Treatment

OTHER_GOV

Sponsor Role: collaborator

Ain Shams University

OTHER

Sponsor Role: lead

Responsible Party

Hadeer Gamal Khalefa

pharmacist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Hadeer G Khalefa, master

Role: PRINCIPAL_INVESTIGATOR

Nassar institute for research and treatment hospital

Locations

AinShams University Hospitals

Cairo, , Egypt

Countries

Egypt

References

Khalefa HG, Shawki MA, Aboelhassan R, El Wakeel LM. Evaluation of the effect of N-acetylcysteine on the prevention and amelioration of paclitaxel-induced peripheral neuropathy in breast cancer patients: a randomized controlled study. Breast Cancer Res Treat. 2020 Aug;183(1):117-125. doi: 10.1007/s10549-020-05762-8. Epub 2020 Jun 29.

Reference Type: DERIVED

PMID: 32601973 (View on PubMed)

Other Identifiers

PHCL93

Identifier Type: -

Identifier Source: org_study_id