Drug Repurposing for the Prevention of Chemotherapy-induced Peripheral Neuropathy (CIPN)

Phase 2

• Conditions: Chemotherapy-induced Peripheral Neuropathy
• Interventions: Drug: Placebo; Drug: Metformin

• Registration Number: NCT04780854
• Lead Sponsor: Cairo University

Brief Summary

Chemotherapy cause many adverse events including induction of peripheral neuropathy. Metformin, the AMPK activator, was found to have protective effect against chemotherapy induced peripheral neuropathy in mouse model and in clinical trials as well. There are different hypothesized mechanisms through which metformin does the protective effect. Such as enhancing mitochondrial activity, reduction of ROS and nitric oxide and activation of AMPK.

Detailed Description

Chemotherapy can cause a variety of side effects. One of the most common side effects is Chemotherapy induced peripheral neuropathy (CIPN), it commonly caused by Paclitaxel chemotherapy which is usually used in the treatment of breast cancer. Metformin which is known as a safe anti-diabetic drug, was found to have a protective effect on neurons. It gave positive results in chemotherapy induced peripheral neuropathy in mouse models and in some clinical trials

Study Timeline

• Study First Submitted: 2020-11-02
• Study Start: 2020-11-03
• Study First Submitted QC: 2021-03-01
• Study First Posted: 2021-03-04
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-27
• Last Update Posted: 2021-07-28
• Primary Completion: 2022-05
• Study Completion: 2022-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 68

Inclusion Criteria

• Age (18-75) male and female patients
• Scheduled to be treated with single agent Paclitaxel
• Performance status according to Eastern Cooperative oncology group (ECOG) < 2.
• Patients who are willing and able to review and provide written consent, patients who can read the questionnaires

Exclusion Criteria

• Previous exposure to chemotherapy drugs that cause neuropathy, patients treated with medications that increase the risk of neuropathy like amiodarone, Colchicine, metronidazole, phenytoin.
• Patients with impaired liver functions or kidney functions.
• Patients with a history of any serious adverse events or interaction or hypersensitivity to Metformin.
• Pregnant or lactating females.
• Patients who are using metformin for any other cause.
• Patients with sensory or motor neuropathy of any grade prior to enrollment.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Metformin-free	Placebo	1 placebo tablet administered twice daily for 3 months
Metformin group	Metformin	1 gm metformin tablet administered twice daily for 3 months

Primary Outcome Measures

Name	Time	Method
Percentage of grade 2-4 neurotoxicity in both arms	3 months	Measured by NCI-CTCAE system

Secondary Outcome Measures

Name	Time	Method
Percentage of other treatment related common adverse events in both arms.	3 months	Graded using NCI-CTCAE system
Difference in biological markers in both arms.	3 months	Measurement of Malondialdehyde (MDA)
Percentage of Qulaity of Life (QOL) deterioration in both arms	3 months	Measured using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group - Neurotoxicity (FACT/GOG-NTX) questionnaire. The higher the score, the better the quality of life.

Trial Locations

Locations (1)

Cairo University; 🇪🇬 Cairo, Egypt