Clinical trial NCT04780854: Drug Repurposing for the Prevention of Chemotherapy-induced Peripheral Neuropathy (CIPN)
Official title: Drug Repurposing for the Prevention of Chemotherapy-induced Peripheral Neuropathy (CIPN)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Chemotherapy-induced Peripheral Neuropathy
Keywords: Cancer
chemotherapy-induced peripheral neuropathy
metformin
neuropathy
Lead sponsor: Cairo University
Sponsor class: OTHER
Collaborators: name: German University in Cairo
First posted: 2021-03-04
Enrollment: 68
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of grade 2-4 neurotoxicity in both arms
timeFrame: 3 months
Secondary outcomes:
measure: Difference in biological markers in both arms.
timeFrame: 3 months
measure: Difference in biological markers in both arms.
timeFrame: 3 months
measure: Percentage of Qulaity of Life (QOL) deterioration in both arms
timeFrame: 3 months
measure: Percentage of other treatment related common adverse events in both arms.
timeFrame: 3 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: Cairo University
Study officials:
affiliation: German University in Cairo
name: Mohamed H. Solayman, PhD. Pharm.
role: STUDY_CHAIR
affiliation: Cairo University
name: Loay M. Kassem, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: German University in Cairo
name: Danira Ashraf Habashy, PhD Pharm.
role: PRINCIPAL_INVESTIGATOR
affiliation: German University in Cairo
name: Sara A. Mosa, Bsc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.22034/APJCP.2018.19.8.2223.
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.
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. Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2014 Jun 20;32(18):1941-67. doi: 10.1200/JCO.2013.54.0914. Epub 2014 Apr 14.