The effect of L-citrulline supplementation on nutrirtional, metabolic, oxidative and inflammatory status and serum levels of L-citrulline and NOx in type 2 diabetes patients: A randomized controlled clinical trial
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Primary outcomes
#1
Measurement of height and weight without shoes and with minimum clothes on, by Seca stadiometer and scale, respectively. Measurement of waist circumference by a tape measure and body mass index (BMI) by dividing weight (kg) by height squared (m2)
Measurement of height and weight without shoes and with minimum clothes on, by Seca stadiometer and scale, respectively. Measurement of waist and hip circumference by a tape measure and body mass index (BMI) by dividing weight (kg) by height squared (m2)
Measurement of height and weight without shoes and with minimum clothes on, by Seca stadiometer and scale, respectively. Measurement of waist and hip circumference by a tape measure and body mass index (BMI) by dividing weight (kg) by height squared (m2)
اندازه گیری قد، وزن بدون کفش و با حداقل لباس ممکن، به ترتیب با استفاده از استفاده از قدسنج و ترازوی Seca، اندازه گیری دور کمر با نوار متری و نمایه توده بدن (BMI) با استفاده از فرمول weight (kg)/height (m)2
اندازه گیری قد، وزن بدون کفش و با حداقل لباس ممکن، به ترتیب با استفاده از استفاده از قدسنج و ترازوی Seca، اندازه گیری دور کمر و دور باسن با نوار متری و نمایه توده بدن (BMI) با استفاده از فرمول weight (kg)/height (m)2
اندازه گیری قد، وزن بدون کفش و با حداقل لباس ممکن، به ترتیب با استفاده از استفاده از قدسنج و ترازوی Seca، اندازه گیری دور کمر و دور باسن با نوار متری و نمایه توده بدن (BMI) با استفاده از فرمول weight (kg)/height (m)2
#2
Measurement of serum hs-CRP by immunoturbidometry method and serum IL-6 and TNF-α by ELISA
Measurement of serum hs-CRP by immunoturbidometry method and serum IL-6, TNF-α, MCP1 and TLR4 by ELISA
Measurement of serum hs-CRP by immunoturbidometry method and serum IL-6 and, TNF-α, MCP1 and TLR4 by ELISA
اندازه گیری hs-CRP سرم با روش ایمونوتوربیدومتری و اندازه گیری اندازه گیری IL-6 و TNF-α سرم به روش ELISA
اندازه گیری hs-CRP سرم با روش ایمونوتوربیدومتری و اندازه گیری IL-6, TNF-α, MCP1 و TLR4 سرم به روش ELISA
اندازه گیری hs-CRP سرم با روش ایمونوتوربیدومتری و اندازه گیری اندازه گیری IL-6 و, TNF-α, MCP1 و TLR4 سرم به روش ELISA
Sponsors / Funding sources
#1
Name of organization / entity - English:
Name of organization / entity - Persian:
Full name of responsible person - English: alireza ostad rahimi
Full name of responsible person - Persian: علیرضا استادرحیمی
Street address - English: Faculty of Nutrition and Food Sciences
Street address - Persian: دانشکده تغذیه و علوم غذایی
City - English: Tabriz
City - Persian: تبریز
Province: East Azarbaijan
Country: Iran (Islamic Republic of)
Postal code: 5166614711
Phone: +98 41 3335 2292
Fax:
Email: nut-rc@tbzmed.ac.ir
Web page address:
Name of organization / entity - English:
Name of organization / entity - Persian:
Full name of responsible person - English: Alireza Ostad Rahimi
Full name of responsible person - Persian: علیرضا استادرحیمی
Street address - English: Faculty of Nutrition and Food Sciences
Street address - Persian: دانشکده تغذیه و علوم غذایی
City - English: Tabriz
City - Persian: تبریز
Province: East Azarbaijan
Country: Iran (Islamic Republic of)
Postal code: 5166614711
Phone: +98 41 3335 2292
Fax:
Email: nut-rc@tbzmed.ac.ir
Web page address:
Name of organization / entity - English: Name of organization / entity - Persian: Full name of responsible person - English: alireza ostad rahimiAlireza Ostad Rahimi Full name of responsible person - Persian: علیرضا استادرحیمی Street address - English: Faculty of Nutrition and Food Sciences Street address - Persian: دانشکده تغذیه و علوم غذایی City - English: Tabriz City - Persian: تبریز Province: East Azarbaijan Country: Iran (Islamic Republic of) Postal code: 5166614711 Phone: +98 41 3335 2292 Fax: Email: nut-rc@tbzmed.ac.ir Web page address:
Protocol summary
Study aim
The aim of the present study is to investigate the effect of L-citrulline supplementation on nutrirtional, metabolic, oxidative and inflammatory status and serum levels of L-citrulline and NOx in type 2 diabetes patients.
Design
Randomized double blind clinical trial with two arm parallel groups
Settings and conduct
Patients volunteering from Tabriz Diabetes Control Center under an endocrinologist with diagnosis of type 2 diabetes will be randomly assigned to one of the two supplement or placebo groups.The duration of the study will be 8 weeks. L-citrulline and placebo sachets will be coded by the person responsible for preparing them, and the main investigators and the patients will be blinded to the type of supplement each group receives.
Participants/Inclusion and exclusion criteria
46 patients with type 2 diabetes and BMI of 25-35 kg / m2 who have been diagnosed with a disease for at least 6 months will be included in the study. Pregnancy, lactation and menopause in women, taking insulin and developing cardiovascular, renal and hepatic diseases are among the exclusion criteria.
Intervention groups
Patients in the L-Citrulline group will use a 3 gram L-Citrulline sachet before their breakfast, daily. In the placebo group, the sachet will contain 3 grams of microcrystalline cellulose.
Main outcome variables
Nutritional status (anthropometric indices , and calorie and macronutrients intake), metabolic status (fasting blood glucose، insulin, HbA1c, Insulin resistance index (HOMA-IR) and lipid profiles (TC, TG, HDL-c LDL-c), oxidative status (total antioxidant capacity, glutathione peroxidase and superoxide dismutase and Malondialdehyde), inflammatory status (hs-CRP, IL-6 and TNF-α), serum levels of L-citrulline and NOx (nitrate and nitrite)
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20100209003320N16
Registration date:2019-06-26, 1398/04/05
Registration timing:prospective
Last update:2019-09-18, 1398/06/27
Update count:2
Registration date
2019-06-26, 1398/04/05
Registrant information
Name
Mehrangiz Ebrahimi mamagani
Name of organization / entity
Health & Nutrition faculty of Tabriz university of medical sciences
Country
Iran (Islamic Republic of)
Phone
+98 41 1335 1113
Email address
ebrahimimamagani@tbzmed.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2019-07-11, 1398/04/20
Expected recruitment end date
2019-09-22, 1398/06/31
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The effect of L-citrulline supplementation on nutrirtional, metabolic, oxidative and inflammatory status and serum levels of L-citrulline and NOx in type 2 diabetes patients: A randomized controlled clinical trial
Public title
The effect of L-Citrulline in type 2 Diabetes
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Suffering from type 2 diabetes that have passed at least 6 months since diagnosis and having HbA1c less than 9.
Men and non-menopausal women
Age 25 to 55 years
BMI 25 to 35 kg/m2
People who control their diabetes just by using metformin and sulfonylurea
Willingness to participate in the study
Exclusion criteria:
Pregnancy, lactation or menopause in women
Smoking or alcohol use
A history of following a particular diet (at the time of the study or 3 months before the study)
Change in the type or dosage of medications consumed, the type and amount of physical activity, changes in the diet at the start and during the study
Using synthetic or herbal drugs for weight loss
Use of any supplement (L-arginine, glutamine, multivitamin, antioxidant supplement, etc.) during the three months before or during the study.
Taking insulin
Suffering from cardiovascular disease, liver, intestinal, thyroid and parathyroid dysfunction, polycystic ovary syndrome, cancers and malignant diseases such as sprue and Crohn's disease
Having symptoms of infectious or inflammatory disease or recent surgery
The use of hypotensive and lipid-lowering drugs
Use of corticosteroids and non-steroidal anti-inflammatory drugs for 3 months before the study.
Age
From 25 years old to 55 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Investigator
Sample size
Target sample size:
46
Randomization (investigator's opinion)
Randomized
Randomization description
46 eligible patients will be randomly allocated to intervention and placebo groups using a software generated random permuted blocks. The generated random sequence will be kept in a protected location and administered by an independent third party who is blind to the trial throughout the study.
Blinding (investigator's opinion)
Double blinded
Blinding description
In this study, the main investigators (including the student and her supervisors and adviser professors), as well as the patients will be blinded to the type of the supplement (L-citrulline or placebo) received by each group. The person responsible for preparing the supplement sachets (who is completely unrelated to the study) will be asked to assign a three-digit code to each of the two powders (L-citrulline and placebo) and keep the codes for himself until the end of the study and data analysis.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
The Research Ethics Committee of Tabriz University of Medical Sciences
Street address
Tabriz University of Medical Sciences, Attar Neishabouri Ave., Golgasht St.
City
Tabriz
Province
East Azarbaijan
Postal code
5166/1573113
Approval date
2019-06-11, 1398/03/21
Ethics committee reference number
IR.TBZMED.REC.1398.216
Health conditions studied
1
Description of health condition studied
Type 2 diabetes
ICD-10 code
E11
ICD-10 code description
Type 2 diabetes mellitus
Primary outcomes
1
Description
Anthropometric Indices
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Measurement of height and weight without shoes and with minimum clothes on, by Seca stadiometer and scale, respectively. Measurement of waist and hip circumference by a tape measure and body mass index (BMI) by dividing weight (kg) by height squared (m2)
2
Description
Calorie and macronutrients intake
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
The intake of calorie and macronutrients from the diet of the subjects with using a 3 day food record questionnaire and analysis by the nutritionist 4 program.
3
Description
Fasting blood sugare
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Enzymatic method
4
Description
Insulin
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
ELISA
5
Description
HbA1c
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Enzymatic method
6
Description
Lipid profile
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Measurement of total cholesterol, HDL- cholesterol and triglyceride through enzymatic methods and calculation of LDL- cholesterol by Friedewald equation
7
Description
Insulin resistance
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Insulin resistance with HOMA-IR and calculation by this equation : [fasting insulin (mU / ml) × fasting glucose (mg / dl)] / 405
8
Description
Oxidative stress indices
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Measurement of total antioxidant capacity, glutathione peroxidase, superoxide dismutase and malondialdehyde through spectrophotometric method
9
Description
Inflammatory indices
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Measurement of serum hs-CRP by immunoturbidometry method and serum IL-6, TNF-α, MCP1 and TLR4 by ELISA
10
Description
Serum levels of L-Citrulline
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
ELISA
11
Description
Serum nitrate and nitrite (NOx)
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Colorimetric with Griess Reagent
Secondary outcomes
1
Description
Physical activity level
Timepoint
Baseline and 8 weeks after intervention
Method of measurement
Via IPAQ questionnaire
Intervention groups
1
Description
Intervention group: Patients in this group will receive L-citrulline supplement for 8 weeks. The supplement is a sachet containing 3 grams of L-Citrulline (a product by Bulk Supplements Co. and made in the United States) which will be dissolved in a glass of water and used once a day before breakfast.
Category
Treatment - Drugs
2
Description
Control group: Patients in this group will receive placebo for 8 weeks. The placebo is a sachet containing 3 grams of microcrystalline cellulose (a product by Linyi Jindi Chemical Co. and made in China) which will be dissolved in a glass of water and used once a day before breakfast.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Tabriz Diabetes Control Center
Full name of responsible person
Dr. Majid Mobasseri
Street address
Sina Hospital, Between the Maralan and Hafez Roads,. Azadi St.
City
Tabriz
Province
East Azarbaijan
Postal code
5163639888
Phone
+98 41 3541 2101
Email
Mobasserim@tbzmed.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Alireza Ostad Rahimi
Street address
Faculty of Nutrition and Food Sciences
City
Tabriz
Province
East Azarbaijan
Postal code
5166614711
Phone
+98 41 3335 2292
Email
nut-rc@tbzmed.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tabriz 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
Tabriz University of Medical Sciences
Full name of responsible person
Samaneh Azizi
Position
Ph.D. student of nutrition sciences
Latest degree
Master
Other areas of specialty/work
Nutrition
Street address
Faculty of Nutrition and Food Sciences., Attar Neishabouri St., Golghast St
City
Tabriz
Province
East Azarbaijan
Postal code
5166614711
Phone
+98 41 3335 7582
Email
s.azizi296@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Dr. Mehrangiz Ebrahimi-Mameghani
Position
professor
Latest degree
Ph.D.
Other areas of specialty/work
Nutrition
Street address
Faculty of Nutrition and Food Sciences., Attar Neyshaburi St., Golghast St
City
Tabriz
Province
East Azarbaijan
Postal code
5166614711
Phone
+98 41 3335 7582
Email
ebrahimimamagani@tbzmed.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Tabriz University of Medical Sciences
Full name of responsible person
Samaneh Azizi
Position
Ph.D. student of nutrition sciences
Latest degree
Master
Other areas of specialty/work
Nutrition
Street address
Faculty of Nutrition and Food Sciences., Attar Neyshaburi St., Golghast St
City
Tabriz
Province
East Azarbaijan
Postal code
5166614711
Phone
+98 41 3335 7582
Email
s.azizi296@gmail.com
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be 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
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available
Title and more details about the data/document
Data collected for the primary outcomes will be shared.
When the data will become available and for how long
Access starting 12 months after publication
To whom data/document is available
The data will only be available for people working in academic institutions.
Under which criteria data/document could be used
The data of the present study will only be accessible by other researchers, for conducting meta-analysis.
What processes are involved for a request to access data/document
The applicant should provide a brief description of the aims and methods of his his Meta-analysis. His request will be assessed and, if agreed, the data will be emailed to the applicant. All these procedures will take no longer than 15 days.