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

Chemotherapy-induced Peripheral Neuropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04780854
• Other study ID #: S-5-2020
• Status: Recruiting
• Phase: Phase 2
• Start date: November 3, 2020
• Est. completion date: July 2022

Study information

• Verified date: July 2021
• Source: Cairo University
• Contact: Sara A. Mosa, Bsc
• Phone: +201008662223
• Email: sara.araby96[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 68
• Est. completion date: July 2022
• Est. primary completion date: May 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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.

Related Conditions & MeSH terms

• Chemotherapy-induced Peripheral Neuropathy
• Peripheral Nervous System Diseases

Intervention

Drug:
• Metformin
Participants in the intervention group will be administered metformin tablets 2 gm daily during the chemotherapy treatment duration
• Placebo
Participants in the placebo group will be administered metformin free tablet as placebo twice daily

Locations

Country	Name	City	State
Egypt	Cairo University	Cairo

Sponsors (2)

Lead Sponsor	Collaborator
Cairo University	German University in Cairo

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

Gaballah A, Shafik A, Elhusseiny K, Ashraf M. Chemotherapy-Induced Peripheral Neuropathy in Egyptian Patients: Single Institution Retrospective Analysis. Asian Pac J Cancer Prev. 2018 Aug 24;19(8):2223-2227. — View Citation

Hershman DL, Lacchetti C, Dworkin RH, Lavoie Smith EM, Bleeker J, Cavaletti G, Chauhan C, Gavin P, Lavino A, Lustberg MB, Paice J, Schneider B, Smith ML, Smith T, Terstriep S, Wagner-Johnston N, Bak K, Loprinzi CL; American Society of Clinical Oncology. P — View Citation

Mao-Ying QL, Kavelaars A, Krukowski K, Huo XJ, Zhou W, Price TJ, Cleeland C, Heijnen CJ. The anti-diabetic drug metformin protects against chemotherapy-induced peripheral neuropathy in a mouse model. PLoS One. 2014 Jun 23;9(6):e100701. doi: 10.1371/journal.pone.0100701. eCollection 2014. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of grade 2-4 neurotoxicity in both arms	Measured by NCI-CTCAE system	3 months
Secondary	Difference in biological markers in both arms.	Measurement of Nerve growth factor (NGF)	3 months
Secondary	Difference in biological markers in both arms.	Measurement of Malondialdehyde (MDA)	3 months
Secondary	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
Secondary	Percentage of other treatment related common adverse events in both arms.	Graded using NCI-CTCAE system	3 months

External Links

•   Impact of Exogenous Neurotropic Factor Administration on Occurrence and Severity of Paclitaxel-Induce Neuropathy in Breast Cancer Patients. An open label Pilot Study
•   Neuropathic Pain and Nerve Growth Factor in Chemotherapy-Induced Peripheral Neuropathy: Prospective Clinical-Pathological Study.
•   Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy.