Back to resultsDrug Repurposing for the Prevention of Chemotherapy-induced Peripheral Neuropathy (CIPN)
Primary Purpose
Chemotherapy-induced Peripheral Neuropathy
Status
Unknown status
Phase
Phase 2
Locations
Egypt
Study Type
Interventional
Intervention
Metformin
Placebo
Sponsored by
About this trial
This is an interventional prevention trial for Chemotherapy-induced Peripheral Neuropathy focused on measuring Cancer, chemotherapy-induced peripheral neuropathy, metformin, neuropathy
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.
Sites / Locations
- Cairo UniversityRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Metformin group
Metformin-free
Arm Description
1 gm metformin tablet administered twice daily for 3 months
1 placebo tablet administered twice daily for 3 months
Outcomes
Primary Outcome Measures
Percentage of grade 2-4 neurotoxicity in both arms
Measured by NCI-CTCAE system
Secondary Outcome Measures
Difference in biological markers in both arms.
Measurement of Nerve growth factor (NGF)
Difference in biological markers in both arms.
Measurement of Malondialdehyde (MDA)
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.
Percentage of other treatment related common adverse events in both arms.
Graded using NCI-CTCAE system
Full Information
NCT ID
NCT04780854
First Posted
November 2, 2020
Last Updated
July 27, 2021
Sponsor
Cairo University
Collaborators
German University in Cairo
1. Study Identification
Unique Protocol Identification Number
NCT04780854
Brief Title
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
2. Study Status
Record Verification Date
July 2021
Overall Recruitment Status
Unknown status
Study Start Date
November 3, 2020 (Actual)
Primary Completion Date
May 2022 (Anticipated)
Study Completion Date
July 2022 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Cairo University
Collaborators
German University in Cairo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
Yes
5. Study Description
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chemotherapy-induced Peripheral Neuropathy
Keywords
Cancer, chemotherapy-induced peripheral neuropathy, metformin, neuropathy
7. Study Design
Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
68 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Metformin group
Arm Type
Active Comparator
Arm Description
1 gm metformin tablet administered twice daily for 3 months
Arm Title
Metformin-free
Arm Type
Placebo Comparator
Arm Description
1 placebo tablet administered twice daily for 3 months
Intervention Type
Drug
Intervention Name(s)
Metformin
Other Intervention Name(s)
N,N-dimethylbiguanide, Cidophage
Intervention Description
Participants in the intervention group will be administered metformin tablets 2 gm daily during the chemotherapy treatment duration
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
inactive pill
Intervention Description
Participants in the placebo group will be administered metformin free tablet as placebo twice daily
Primary Outcome Measure Information:
Title
Percentage of grade 2-4 neurotoxicity in both arms
Description
Measured by NCI-CTCAE system
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Difference in biological markers in both arms.
Description
Measurement of Nerve growth factor (NGF)
Time Frame
3 months
Title
Difference in biological markers in both arms.
Description
Measurement of Malondialdehyde (MDA)
Time Frame
3 months
Title
Percentage of Qulaity of Life (QOL) deterioration in both arms
Description
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.
Time Frame
3 months
Title
Percentage of other treatment related common adverse events in both arms.
Description
Graded using NCI-CTCAE system
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sara A. Mosa, Bsc
Phone
+201008662223
Email
sara.araby96@gmail.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mohamed H. Solayman, PhD. Pharm.
Organizational Affiliation
German University in Cairo
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Loay M. Kassem, PhD
Organizational Affiliation
Cairo University
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Danira Ashraf Habashy, PhD Pharm.
Organizational Affiliation
German University in Cairo
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sara A. Mosa, Bsc
Organizational Affiliation
German University in Cairo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cairo University
City
Cairo
Country
Egypt
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Loay Kassem
First Name & Middle Initial & Last Name & Degree
Loay Kassem
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
30139229
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.
Results Reference
background
PubMed Identifier
24955774
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.
Results Reference
background
PubMed Identifier
24733808
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.
Results Reference
result
Links:
URL
https://www.frontiersin.org/articles/10.3389/fnmol.2017.00174/full
Description
Pathophysiology of Chemotherapy-Induced Peripheral Neuropathy.
URL
https://resoncol.journals.ekb.eg/article_8341_1085.html
Description
Impact of Exogenous Neurotropic Factor Administration on Occurrence and Severity of Paclitaxel-Induce Neuropathy in Breast Cancer Patients. An open label Pilot Study
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Drug Repurposing for the Prevention of Chemotherapy-induced Peripheral Neuropathy (CIPN)
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