Clinical trial NCT03492047: N-acetyl Cysteine Effect in Peripheral Neuropathy in Cancer Patients
Official title: Evaluation of The Effect of N-AcetylCysteine in The Prevention of Paclitaxel-Induced Peripheral Neuropathy in Cancer Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Peripheral Neuropathy Due to Chemotherapy
Keywords: paclitaxel
peripheral neuropathy
N-acetyl cysteine
Lead sponsor: Ain Shams University
Sponsor class: OTHER
Collaborators: name: Nasser Institute For Research and Treatment
First posted: 2018-04-10
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Incidence of chemotherapy induced-peripheral neuropathy
timeFrame: up to 12 week
Secondary outcomes:
measure: severity of chemotherapy induced-peripheral neuropathy
timeFrame: at baseline and before each cycle up to 12 week
measure: Adverse effects
timeFrame: at baseline and each cycle up to 12 week
measure: severity of chemotherapy induced-peripheral neuropathy
timeFrame: at baseline, at the end of 6 cycle and at the end of 12 cycles
Other outcomes:
measure: the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity(FACT-GOG-NTX) subscale
timeFrame: weekly up to 12 week
measure: serum nerve growth factor
timeFrame: at baseline and after 12 week
measure: serum malionaldehyde
timeFrame: at baseline and after 12 week
Locations:
city: Cairo
country: Egypt
facility: AinShams University Hospitals
Study officials:
affiliation: Nassar institute for research and treatment hospital
name: Hadeer G Khalefa, master
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.