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Protocol summary

Study aim
Determining the effect of resveratrol supplementation on the expression of some genes mediating immunity and inflammation, inflammatory factors, oxidative stress, and clinical outcomes in patients with acute ischemic stroke receiving enteral nutrition hospitalized in the intensive care unit
Design
A controlled, parallel-group, triple-blind, randomized, phase 3 clinical trial on 60 patients with acute ischemic stroke, randomized blocks
Settings and conduct
The study will take place at the Firouzgar Hospital. Patients will be randomly assigned to two groups: Resveratrol (containing 250 mg of resveratrol and 10 mg of grape skin extract) TDS (30 people); and placebo (containing maltodextrin, similar to resveratrol capsules)TDS (30 people) for 28 days. Stroke severity will be measured using the NIHSS Stroke Scale. At the beginning and end of the study, 10 cc of IV blood samples will be collected from participants. Mononuclear cells will be extracted from these samples to perform quantitative real-time PCR, and RNA will be extracted and converted into cDNA using a kit. Serum levels of IL-1β and IL-6 will be evaluated using a kit and ELISA method. The serum total antioxidant capacity and serum malondialdehyde level will be evaluated using a kit and calorimetric method. The researcher, the neurologist, individuals involved in blood collection and sample evaluation, and the person performing statistical analysis will all be blinded.
Participants/Inclusion and exclusion criteria
Patients with acute ischemic stroke receiving enteral nutrition admitted to the intensive care unit
Intervention groups
Resveratrol capsules containing 250 mg of resveratrol and 10 mg of grape skin extract three times a day, equivalent to 750 mg of resveratrol and 30 mg of grape skin extract, placebo capsule (containing maltodextrin)
Main outcome variables
IL-1β gene expression; Stroke severity score NIHSS

General information

Reason for update
Due to the low number of eligible patients and lack of patient recruitment, the design will be multicentered. The study will be conducted in the Stroke ICU of Firoozgar Hospital, the Intensive Care Unit of Shohadaye Tajrish Hospital of Shahid Beheshti University of Medical Sciences, the Intensive Care Unit of Sina Hospital of Tehran University of Medical Sciences, and the Intensive Care Unit of Rasoul Akram Hospital. According to the studies, we reduce the duration of the intervention to 28 days. The sample size, with the calculation of 20% drop out of the study, will be 60 patients. The responsible person in Firouzgar Hospital changed. The percentage of financial support was incorrectly written as 26%, but it was corrected to 100%.
Acronym
IRCT registration information
IRCT registration number: IRCT20091114002709N61
Registration date: 2023-07-24, 1402/05/02
Registration timing: prospective

Last update: 2024-12-27, 1403/10/07
Update count: 1
Registration date
2023-07-24, 1402/05/02
Registrant information
Name
Farzad Shidfar
Name of organization / entity
Iran University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 21 8862 2755
Email address
shidfar.f@iums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2024-12-30, 1403/10/10
Expected recruitment end date
2025-12-31, 1404/10/10
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effects of resveratrol supplement on some mediator genes of immunity and inflammation, inflammatory factors, oxidative stress and clinical outcomes in hospitalized acute ischemic stroke patients with enteral feeding in intensive care unit: A randomized triple-blind placebo-controlled trial
Public title
Resveratrol in acute ischemic stroke
Purpose
Supportive
Inclusion/Exclusion criteria
Inclusion criteria:
Willingness to cooperate and complete the informed consent form by the patient or legal guardian, patients aged 18-85 years, body mass index ≤ 35 kg/m2, starting the intervention within 24 hours after being admitted to the ICU and not spending More than 24 hours from the time of disease diagnosis until the time of entering the study, the severity of stroke based on the NIHSS standard is higher than 4, the patient's GCS at the time of visit is higher than 3, feeding by enteral feeding method, receiving at least 80 percent of the prescribed formula during the first 48 hours, none Absolute contraindications for enteral feeding (permanent ileus, ischemia of the digestive tract, bilious or continuous vomiting and mechanical obstruction), the possibility of hospitalization in the intensive care unit (ICU) for 28 days, not suffering from hepatic encephalopathy and liver cirrhosis, not suffering from metastatic cancer, not having infection and sepsis, not having AIDS (HIV), not having hepatitis, not receiving supplements or formulas that strengthen the immune system, including arginine, glutamine, colostrum, vitamins C and E, selenium, zinc or Omega-3 fatty acids or resveratrol supplement during the last 30 days before the start of the intervention, not suffering from allergies or intolerance to the enteral formula used in the present study and resveratrol supplement, non-participation in other interventional studies. No company in the past 30 days in other clinical trial studies at the same time as the present study
Exclusion criteria:
Pregnancy, lactation, intracranial hemorrhage, history of previous stroke, consumption of any natural food containing resveratrol within 48 hours before the onset of stroke, patients who received rtPA, more than 24 hours from onset of symptoms, seizure at onset Stroke, intracranial hemorrhage, symptoms suggestive of subarachnoid hemorrhage, rapid recovery or partial symptoms, stroke severity based on NIHSS criteria less than 4, patient suffering from dementia before stroke
Age
From 18 years old to 85 years old
Gender
Both
Phase
3
Groups that have been masked
  • Participant
  • Care provider
  • Investigator
  • Outcome assessor
  • Data analyser
Sample size
Target sample size: 60
Randomization (investigator's opinion)
Randomized
Randomization description
If they meet the criteria for entering the study, they will be placed in one of the two study groups based on age (18-65 and ≥65) and gender. Randomization will be done using the Block Randomization technique using the Sealed Envelope online site. The random code of this study will be generated electronically using the block of four technique online site.
Blinding (investigator's opinion)
Triple blinded
Blinding description
Resveratrol will be purchased from Raha company, its purity is 100% and its type is trans, and the placebo will be made by the Faculty of Pharmacy of Iran University of Medical Sciences. Drug treatment will be similar in both groups. Random codes will be placed in sealed envelopes. All researchers, participants, and laboratory technicians will be blinded to the patient allocation process and intervention content. All the data is coded by another person who does not intervene in the study at first, and the person who analyzes the obtained data does not know about the process of allocating patients until the end, and thus the study will be three-way blind. Supplements and placebo are placed in similar containers. They will be coded as groups A and B by a person other than the researcher outside the study so that the researcher is unaware of the contents of the capsules, and in this way, the researcher is not aware of the drug and placebo. Blinding is done so that the lack of knowledge of the type of supplements each group receives is considered.
Placebo
Used
Assignment
Parallel
Other design features

Secondary Ids

empty

Ethics committees

1

Ethics committee
Name of ethics committee
Research Ethics Committees of Iran University of Medical Sciences
Street address
Shahid Hemmat Highway
City
Tehran
Province
Tehran
Postal code
14496-14535
Approval date
2024-12-22, 1403/10/02
Ethics committee reference number
IR.IUMS.REC.1402.293

Health conditions studied

1

Description of health condition studied
Acute ischemic stroke
ICD-10 code
I63.9
ICD-10 code description
Cerebral infarction, unspecified

Primary outcomes

1

Description
IL-1β gene expression
Timepoint
At the beginning of the study and 28th day
Method of measurement
Real-time PCR

2

Description
Stroke severity score NIHSS: National Institutes of Health Stroke Scale
Timepoint
At the beginning of the study and 28th day
Method of measurement
Physical examination

Secondary outcomes

1

Description
NLRP3 gene expression
Timepoint
At the beginning of the study and 28th day
Method of measurement
Real-time PCR

2

Description
ASC gene expression
Timepoint
At the beginning of the study and 28th day
Method of measurement
Real-time PCR

3

Description
Caspase-1gene expression
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
Real-time PCR

4

Description
Serum levels of IL-1β
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
By ELISA kit

5

Description
Serum levels of IL-6
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
By ELISA kit

6

Description
Serum total antioxidant capacity
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
Colorimetric

7

Description
Serm malondialdehyde (MDA) level
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
Colorimetric

8

Description
Barthel Index
Timepoint
28 days after the end of the intervention and 90 days after the end of the intervention
Method of measurement
Based on specific forms that the patient or his / her companions will be asked by phone or in person.

9

Description
Modified Rankin Scale (MRS)
Timepoint
28 days after the end of the intervention and 90 days after the end of the intervention
Method of measurement
Based on specific forms that the patient or his / her companions will be asked by phone or in person.

10

Description
APACHE II score
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
in this study, APACHEII questionnaire will be complimented.

11

Description
SOFA score
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
in this study, SOFA questionnaire will be complimented.

12

Description
NUTRIC score
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
in this study, NUTRIC score questionnaire will be complimented.

13

Description
Mini-Mental State Examination (MMSE)
Timepoint
90 days after the end of the intervention
Method of measurement
in this study, MMSE score questionnaire will be complimented.

14

Description
Anthropometric indices
Timepoint
At the beginning of the study and after twenty-eight days of intervention
Method of measurement
Physical examination

Intervention groups

1

Description
Intervention group: Resveratrol capsules containing 250 mg of resveratrol and 10 mg of grape skin extract three times a day, equivalent to 750 mg of resveratrol and 30 mg of grape skin extract
Category
Treatment - Other

2

Description
Control group: Daily intake of placebo for 28 days
Category
Placebo

Recruitment centers

1

Recruitment center
Name of recruitment center
Firouzgar educational, research and treatment, center
Full name of responsible person
Tara Khoeini
Street address
Beh Afarin St., Karim Khan Zand Blvd., Tehran, Iran
City
Tehran
Province
Tehran
Postal code
1593747811
Phone
+98 21 8214 1000
Email
h_firoozgar@yahoo.com

2

Recruitment center
Name of recruitment center
Shohadaye Tajrish Hospital
Full name of responsible person
سید حسین اردهالی
Street address
Shahrdari Street,Tajrish Sqr
City
Tehran
Province
Tehran
Postal code
1989934148
Phone
+98 21 2271 8000
Fax
Email
pr-shohada@sbmu.ac.ir

3

Recruitment center
Name of recruitment center
Sina Hospital
Full name of responsible person
Gelareh Banihashemi
Street address
Hassan-Abad Square, Imam-Khomeini Ave
City
Tehran
Province
Tehran
Postal code
1136746911
Phone
+98 21 6634 8500
Email
hosp_sina@sina.tums.ac.ir

4

Recruitment center
Name of recruitment center
Hazrat Rasul Akram educational, research and treatment complex
Full name of responsible person
Omid Moradimoghadam
Street address
Starkhan-Niyaish Street-Corner of Mansouri Street
City
Tehran
Province
Tehran
Postal code
1445613131
Phone
+98 21 6435 1000
Email
rasoolhospital@iums.ac.ir

Sponsors / Funding sources

1

Sponsor
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Reza Falak
Street address
Iran University of Medical Sciences (IUMS), Shahid Hemmat Highway, Tehran, IRAN
City
Tehran
Province
Tehran
Postal code
14496-14535
Phone
+98 21 8670 2030
Email
rezafalak@yahoo.com
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Iran 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
Iran University of Medical Sciences
Full name of responsible person
Farzad shidfar
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, IRAN
City
Tehran
Province
Tehran
Postal code
1449614535
Phone
+98 21 8860 2218
Fax
+98 21 8860 2219
Email
farzadshidfar@yahoo.com

Person responsible for scientific inquiries

Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Farzad shidfar
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, IRAN
City
Tehran
Province
Tehran
Postal code
1449614535
Phone
+98 21 8670 4743
Fax
+98 21 8860 2219
Email
farzadshidfar@yahoo.com

Person responsible for updating data

Contact
Name of organization / entity
Iran University of Medical Sciences
Full name of responsible person
Farzad shidfar
Position
Professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Iran University of Medical Sciences, Shahid Hemmat Highway, Tehran, IRAN
City
Tehran
Province
Tehran
Postal code
1449614535
Phone
+98 21 8670 4743
Fax
+98 21 8860 2219
Email
farzadshidfar@yahoo.com

Sharing plan

Deidentified Individual Participant Data Set (IPD)
Yes - There is a plan to make this available
Study Protocol
Yes - There is a plan to make this available
Statistical Analysis Plan
Yes - There is a plan to make this available
Informed Consent Form
Yes - There is a plan to make this available
Clinical Study Report
Yes - There is a plan to make this available
Analytic Code
Yes - There is a plan to make this available
Data Dictionary
Yes - There is a plan to make this available
Title and more details about the data/document
All data is potentially shareable after de-identifying individuals
When the data will become available and for how long
The access period starts 6 months after the results are published
To whom data/document is available
Only for researchers working in academic and scientific institutions
Under which criteria data/document could be used
In order to use the data to conduct another study or use in patients
From where data/document is obtainable
Dr Farzad Shidfar, shidfar.f@iums.ac.ir
What processes are involved for a request to access data/document
Request by e-mail along with providing a complete explanation of why the data is needed
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