Evaluation of Melatonin efficacy in prophylaxis of Doxorubicin induced cardiotoxicity in patients with breast cancer and receiving the Doxorubicin-Cyclophosphamide regimen : Double-blind randomized clinical trial
Evaluation of the effectiveness of melatonin in preventing doxorubicin-induced cardiac toxicity in patients with breast cancer receiving AC regimen
Design
The clinical trial has a control group with parallel groups that is performed in two blind, randomized, phase 3 and on 58 patients. Block randomization method is used for randomization.
Settings and conduct
This study was performed at the Imam Khomeini Hospital Cancer Institute, Tehran University of Medical Sciences, with the aim of investigating the possibility of prescribing Melatonin to prevent the occurrence of doxorubicin-induced cardiac toxicity in breast cancer patients and on 58 patients who are in two groups. Patients in the two groups are compared in terms of criteria including: blood levels of cardiac biomarkers and echocardiographic results.
Participants/Inclusion and exclusion criteria
- People who have recently been definitively diagnosed with breast cancer and are candidates for a chemotherapy regimen containing doxorubicin
Intervention groups
Patients are divided into two groups. In the first group, Melatonin is prescribed with a chemotherapy regimen and in the second group, the same chemotherapy regimen is prescribed with a Placebo.
Main outcome variables
- Echocardiographic variables including: EF and GLS
- Cardiac biomarkers including troponin and CK-MB
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20211109053025N1
Registration date:2022-01-07, 1400/10/17
Registration timing:registered_while_recruiting
Last update:2022-01-07, 1400/10/17
Update count:0
Registration date
2022-01-07, 1400/10/17
Registrant information
Name
Seyed Mohamad Mousavinia
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 21 6658 1692
Email address
sm_mousavinia@razi.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2021-11-22, 1400/09/01
Expected recruitment end date
2022-08-22, 1401/05/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of Melatonin efficacy in prophylaxis of Doxorubicin induced cardiotoxicity in patients with breast cancer and receiving the Doxorubicin-Cyclophosphamide regimen : Double-blind randomized clinical trial
Public title
Evaluation of Melatonin efficacy in prophylaxis of Doxorubicin induced cardiotoxicity in patients with breast cancer and receiving the Doxorubicin-Cyclophosphamide regimen
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
People who have recently been definitively diagnosed with breast cancer and are candidates for a chemotherapy regimen containing doxorubicin
Having the consent to participate in the study
Age over 18 years
Ability to consume orally
Normal liver function (serum bilirubin less than 1.5 mg / dl)
No CKD or SrCreatinine> 2 mg / dL or eGFR <30 mL / min / m2
Exclusion criteria:
Patients with a history of breast cancer or a history of chemotherapy drugs that cause cardiotoxicity
Patients who are unable to receive doxorubicin for any reason
Patient with LVEF <50% before starting treatment
Use of ACE inhibitors, ARBs, beta-blockers or in the treatment of heart failure
Having coronary or valvular heart disease, cardiomyopathy, hypertension or AF
History of receiving chest radiotherapy
Patients with neurological injuries such as Parkinson's, stroke, seizures, etc.
Those who are taking an antioxidant drug such as vitamin E, NAC, etc.
Participate in other clinical studies simultaneously
Known sensitivity to any of the consumables in the study
Age
From 18 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Data and Safety Monitoring Board
Sample size
Target sample size:
56
Randomization (investigator's opinion)
Randomized
Randomization description
Patients are randomly assigned to the study using block randomization in two groups receiving placebo chemotherapy regimen or melatonin chemotherapy regimen group. For this purpose, the patient and the researcher (student) and the doctors will be blind and the randomization operation will be performed by the executor of the project based on double or quadruple random tables and on each box, a number will be registered, the contents of which will be unknown, and in this way it will be given to the researcher and then the patient.
Blinding (investigator's opinion)
Double blinded
Blinding description
Participants in the study, the physician who introduced them to the research team, the cardiologist who is responsible for measuring echocardiographic parameters in patients in both groups, and the laboratory staff who are responsible for measuring cardiac biomarkers in patients, the student who, as a researcher, makes the arrangements are blinded in this study. Using block randomization method which is done by the executor of the project and using two or four tables, each box containing the medicine or placebo is randomly assigned a number and that number is given to the researcher and the patient.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
The Institute of Pharmaceutical Sciences (TIPS) of the Tehran University of Medical Sciences
Street address
Poursina Avenue, Tehran University of Medical Sciences, Faculty of Pharmacy, The Institute of Pharmaceutical Sciences (TIPS), PO Box. 14176-13151, Iran
City
Tehran
Province
Tehran
Postal code
14176-13151
Approval date
2021-12-25, 1400/10/04
Ethics committee reference number
IR.TUMS.TIPS.REC.1400.19
Health conditions studied
1
Description of health condition studied
Breast cancer
ICD-10 code
C50
ICD-10 code description
Malignant neoplasm of breast
2
Description of health condition studied
drug-induced cardiomyopathy
ICD-10 code
142.7
ICD-10 code description
cardiomyopathy due to drug and external agent
Primary outcomes
1
Description
LVEF (Left ventricular ejection fraction) : The left ventricular drain fraction or the amount of blood pumped from the left ventricle with each contraction.
Timepoint
Once at the beginning and once a week after the last chemotherapy session
Method of measurement
Using echocardiography performed by a cardiologist
Secondary outcomes
1
Description
GLS (Global longitudinal strain): A sensitive criterion used by echocardiography to measure myocardial deformity and left ventricular contractile strength and can aid in the early diagnosis of cardiotoxicity. A decrease of more than 15% compared to the beginning or an absolute value of -19% after the start of anthracyclines is associated with a significant increase in the risk of future LVEF reduction.
Timepoint
At the beginning and one week after the last chemotherapy session
Method of measurement
Echocardiography by a cardiologist
2
Description
Troponin I: One of the three types of troponin present in the body that is more specific to the myocardium of the heart and as a marker of the heart, can help diagnose myocardial damage. This enzyme increases within a few hours after heart damage and can last for a long time. Remain in my head for 10-14 days.
Timepoint
Once at the beginning and twice at one week after the second and last session of chemotherapy
Method of measurement
Blood sampling and blood level measurement by laboratory
3
Description
CK-MB: Creatine kinase and its MB isoenzyme are among the serological tests used to diagnose heart damage. This biomarker rises within the first 4 to 6 hours after heart injury and returns to baseline after 36 to 48 hours.
Timepoint
Once at the beginning and twice at one week after the second and last session of chemotherapy.
Method of measurement
Blood sampling and blood level measurement by laboratory
4
Description
PSQI Score: The Pittsburgh Sleep Quality Index Questionnaire examines people's attitudes about sleep quality over the past four weeks. It has 7 components and each component gets a score from zero to three. The overall score is from zero to 21 and is obtained from the sum of the scores of the components. An overall score of 5 or higher indicates poor sleep quality.
Timepoint
At the beginning, a month later and at the end of chemotherapy
Method of measurement
Using the PSQI questionnaire
5
Description
ISI (Insomnia severity index) score: The index indicates the severity of insomnia, which includes 5 questions with intensity and scores from zero to 4. In the end, based on the overall score, which is from zero to 28, the severity of insomnia is determined.
Timepoint
At the beginning, a month later and at the end of chemotherapy
Method of measurement
ISI questionnaire
6
Description
HADS (Hospital Anxiety and Depression Scale) Score: A clinical scale for anxiety and depression that includes 14 questions. The score of the individual questions is the index of anxiety and the couple questions are the index of depression. The total score varies from zero to 21 and based on that, the person is defined as normal or abnormal.
Timepoint
At the beginning, a month later and at the end of chemotherapy
Method of measurement
HADS questionnaire
7
Description
EORTC score QLQ-c30: is a quality of life questionnaire in cancer patients that has been done in Persian for reliability and validity. Each question receives a score from 1 to 4 and is finally determined based on the total score of quality of life .
Timepoint
First, one month later and end of the study
Method of measurement
Score from the questionnaire
Intervention groups
1
Description
Intervention group: A group in which patients receive melatonin drug produced by Jalinous at a dose of 10 mg once in the evening along with chemotherapy. The patient will receive this drug from the first day of chemotherapy until one week after the last session. The duration of medication will be 49 or 70 days, depending on the patient's chemotherapy regimen.
Category
Prevention
2
Description
Control group: A group in which patients receive Placebo produced by Jalinous once in the evening along with chemotherapy. The patient will receive placebo from the first day of chemotherapy until one week after the last session. The duration of medication will be 49 or 70 days, depending on the patient's chemotherapy regimen.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Imam Khomeini Hospital Cancer Institute
Full name of responsible person
Seyed Mohamad Mousavinia
Street address
Dr. Gharib Street, the end of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1419733141
Phone
+98 21 6119 2690
Email
s.m_mousavinia@yahoo.com
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Dr.Mojgan Karbakhsh Davari
Street address
sixth floor, University Central Organization, corner of Quds Street, Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1417653761
Phone
+98 21 8163 3685
Email
vcr@tums.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Seyed Mohamad Mousavinia
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Cancer Institute, Imam Khomeini Hospital, Dr. Gharib St. , End of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1599957113
Phone
+98 21 6658 1692
Fax
Email
sm_mousavinia@razi.tums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Seyed Mohamad Mousavinia
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Cancer Institute, Imam Khomeini Hospital, Dr. Gharib St. , End of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1599957113
Phone
+98 21 6658 1692
Fax
Email
sm_mousavinia@razi.tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Seyed Mohamad Mousavinia
Position
Resident
Latest degree
Medical doctor
Other areas of specialty/work
Medical Pharmacy
Street address
Cancer Institute, Imam Khomeini Hospital, Dr. Gharib St. , End of Keshavarz Boulevard
City
Tehran
Province
Tehran
Postal code
1599957113
Phone
+98 21 6658 1692
Fax
Email
sm_mousavinia@razi.tums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
No - There is not a plan to make this available
Justification/reason for indecision/not sharing IPD
it is not necessary
Study Protocol
No - There is not a plan to make this available
Statistical Analysis Plan
No - There is not a plan to make this available
Informed Consent Form
No - There is not a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
No - There is not a plan to make this available
Data Dictionary
Not applicable
Title and more details about the data/document
Final proposal report
When the data will become available and for how long
one year
To whom data/document is available
Researchers
Under which criteria data/document could be used
For other researchers to use the results of the data
From where data/document is obtainable
To the main executor of the project
What processes are involved for a request to access data/document