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

Study Overview
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Brief Summary
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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
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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

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

Conditions
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Chemotherapy-induced Peripheral Neuropathy

Intervention / Treatment
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* Drug: Metformin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Metformin group<br>1 gm metformin tablet administered twice daily for 3 months | Drug: Metformin<br>* Participants in the intervention group will be administered metformin tablets 2 gm daily during the chemotherapy treatment duration<br>* Other names: Cidophage;|
| Placebo Comparator: Metformin-free<br>1 placebo tablet administered twice daily for 3 months | Drug: Placebo<br>* Participants in the placebo group will be administered metformin free tablet as placebo twice daily<br>* Other names: inactive pill;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of grade 2-4 neurotoxicity in both arms | Measured by NCI-CTCAE system | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in biological markers in both arms. | Measurement of Nerve growth factor (NGF) | 3 months | 
| Difference in biological markers in both arms. | Measurement of Malondialdehyde (MDA) | 3 months | 
| Percentage of Qulaity of Life (QOL) deterioration in both arms | 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. | 3 months | 
| Percentage of other treatment related common adverse events in both arms. | Graded using NCI-CTCAE system | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cancer, chemotherapy-induced peripheral neuropathy, metformin, neuropathy