The effect of adding synbiotic supplement to the regimen of treating patients with rheumatoid arthritis for 3 months on the severity of the disease
Design
Two arm parallel group (1 synbiotic group and another placebo control group) randomised trial with blinded post-therapeutic care and outcome assessment.
Settings and conduct
Patients who attended Isfahan Al Zahra hospital Rheumatology clinic with RA
Participants/Inclusion and exclusion criteria
INCLUSION criteria: patients who diagnosed with RA based on ACR criteria; at least 3 months passed from diagnosis; Age 18 to 80 years ; At least 4 swollen joints which were stable for at least 1 month with corticosteroids & methotrexate (DMARD);
EXCLUSION criteria:
No willingness to give informed consent; Allergic to probiotics; probiotic use (food or drug) in the last 2 weeks; IBD; perforated bowel; existence of surgical plan in the study time course; renal or hepatic disease, Cushing, DM, thyroid disease,; use of antibiotics in the last month; weight loss regimen; smoking; antioxidant user; participating in any other clinical trial; biologic agents user; discontinuation of participation by the patient.
Intervention groups
Two groups, in addition to corticosteroids and methotrexate that were given to all patients (standard therapy of RA) synbiotic for group 1 and placebo for group 2 were prescribed.
Main outcome variables
RA severity; RA activity
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20121216011763N37
Registration date:2019-06-25, 1398/04/04
Registration timing:retrospective
Last update:2019-06-25, 1398/04/04
Update count:0
Registration date
2019-06-25, 1398/04/04
Registrant information
Name
Gholamreza Askari
Name of organization / entity
Isfahan University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 31 1792 2110
Email address
askari@mui.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2019-03-02, 1397/12/11
Expected recruitment end date
2019-06-01, 1398/03/11
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Evaluation of symbiotic supplementation on the disease activity in rheumatoid arthritis
Public title
Effect of symbiotic supplementation in rheumatoid arthritis
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Rheumatoid arthritis patients (based on ACR criteria)
At least 3 months after the diagnosis of RA.
At least 4 swollen joints which were in a stable status for at least 1 month, on MTX and prednisolone
Exclusion criteria:
Drug reaction and hypersensitivity
patient dissatisfaction
consumption of probiotic oral or medical in the last 2 weeks
IBD
intestinal perforation
creatinine clearance by using the CKD-EPI equation of less than 40 mL/min per 1.73 m2
aspartate and alanine aminotransferase levels greater than twice the upper limit of normal
active or recent hepatitis or cirrhosis
plan for surgery in the next 3 months
thyroid disorders
Cushing's disease or syndrome
malignant tumors,
inadequately controlled diabetes mellitus or arterial hypertension
serious infections,
serious cardiac or respiratory diseases, leukopenia or thrombocytopenia,
inadequate contraception, pregnancy or a plan for it in the next 3 months, breastfeeding,
osteoporosis,
use of cytotoxic or immunosuppressive drugs for 3 months before inclusion,
current or past substance abuse (including tobacco) or alcohol use greater than 2 U/d
and psychological illnesses or intellectual disorders that would preclude adherence to the study protocol
Age
From 18 years old to 80 years old
Gender
Both
Phase
N/A
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
200
Randomization (investigator's opinion)
Randomized
Randomization description
Randomization sequence was generated using STATA 14 statistical software and was stratified with a 1:1 allocation using random block size of 2. Sex, MTX and prednisolone doses were involved in stratification. The Pts were assigned to the MTX-prednisolone based treatment strategy combined with either 1000 mg/day symbiotic supplement (MTX and prednisone PLUS symbiotic group), or placebo (MTX and prednisolone PLUS placebo group) groups following stratified randomization procedures. The symbiotic and placebo were in capsule forms and identical in shape, size, count and also, similar in the appearance of the opaque bottles in which drugs were prepared and numbered, by computer, for each patient. Then bottles were put in 2 black boxes by a "research-blinded rheumatology clinic secretary" to hide the sequence from the main researchers (Esmaili F. and Salesi M.) enrolling and assessing participants. To ensure adequate concealment from the researchers, drugs were administered to the patients by another "research-blinded rheumatology clinic secretary", after the subjects completed all baseline assessments and also, after they signed the informed consent. The statistical sequence of the classified blocks was prepared for the participants by Professor Merasi. The details of the series were unknown to the main investigators (Dr. Esmaili and Dr. Salesi). Main investigators enrolled the participants with ignorance to the allocation sequence and the drugs were put in to two boxes by a secretary and were administered by another.
Blinding (investigator's opinion)
Double blinded
Blinding description
This study was a double-blind clinical trial (participant, researcher). The lactocare synbiotic supplement and its placebo, were produced by Zist takhmir company. Synbiotic supplement and its placebos were put in the same form of package and the patients and researcher were not aware of the content of the package until the end of trial.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Isfahan univesity of medical sciences
Street address
Isfahan, Hezarjirib street
City
Isfahan
Province
Isfehan
Postal code
8174673461
Approval date
2019-03-02, 1397/12/11
Ethics committee reference number
IR.MUI.MED.REC.1397.281
Health conditions studied
1
Description of health condition studied
Rheumatoid Arthritis
ICD-10 code
M05
ICD-10 code description
Rheumatoid arthritis with rheumatoid factor
Primary outcomes
1
Description
Severity of disease activity
Timepoint
At the beginning of the study and 3 months after starting the drug
Method of measurement
Physical examination for the number of tender joint (T1) and swellen j (S1) and blood tests (ESR, CRP, ALT, Cr), calculate DAS28 according to ESR, Tender Joint, Sowllen joint and VAS dat
Secondary outcomes
empty
Intervention groups
1
Description
Intervention group During the 3 months of our study, we used steroid and DMARD (methotrexate) and synbiotic. This supplement made by the Lactocare brand was made by the biomarker knowledge-based company. In the form of capsules of 500 mg contains 7 probiotic strains with a dose of one billion CFUs and prebiotic fructooligosaccharide. All probiotic strains of this supplement had positive effects on inflammatory control: Lacobacillus casei, Lacobacillus asidophilus, Lacobacillus rhmnosus, Lacobacillus bugaricus, Bifidobacterium breve, Bifidobacterium longun, Streptococcus thermophiles. How to administer supplements was that in 3 months Intervention: Two capsules were consumed every day after lunch
Category
Treatment - Other
2
Description
Control group: Individuals over the course of 3 months, our study of steroids and DMARD (methotrexate) and placebo (containing starch) received two capsules daily after lunch. The placebo is made in the biomarker company and were be available to patients in the form of capsules of the same type as synbiotic.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Alzahra hospital
Full name of responsible person
Mansour Salesi
Street address
Shohadaie Sofeh Ave.
City
Esfahan
Province
Isfehan
Postal code
8158168131
Phone
+98 31 3263 0565
Email
askari@mui.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
the University of medical sciences Esfahan
Full name of responsible person
Shaghayegh Haghjou
Street address
Hezargrib Ave
City
Isfahan
Province
Isfehan
Postal code
8174673461
Phone
+98 31 3888 0048
Email
sh_haghjoo@med.mui.ac.ir
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
the University of medical sciences Esfahan
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
Esfahan University of Medical Sciences
Full name of responsible person
فرح اسماعیلی
Position
َAssociate professor
Latest degree
Specialist
Other areas of specialty/work
Internal Medicine
Street address
Shohadaye Soffeh Ave.,Alzahra Hospital
City
Esfahan
Province
Isfehan
Postal code
81366665
Phone
+98 31 3431 7469
Email
dr.esmaili.270288@gmail.com
Person responsible for scientific inquiries
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Mansour Salesi
Position
Professor
Latest degree
Specialist
Other areas of specialty/work
Internal Medicine
Street address
Shohadai Soffeh Ave.,Alzahra hospital
City
Esfahan
Province
Isfehan
Postal code
8166665
Phone
+98 31 3431 7469
Email
Mansour1380@yahoo.com
Person responsible for updating data
Contact
Name of organization / entity
Esfahan University of Medical Sciences
Full name of responsible person
Farah Esmaili
Position
Associate Professor
Latest degree
Specialist
Other areas of specialty/work
Internal Medicine
Street address
Shohadaie Soffeh Ave.,Alzahra hospital
City
Esfahan
Province
Isfehan
Postal code
81366665
Phone
+98 31 3431 7469
Email
dr.esmaili.270288@gmail.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
Undecided - It is not yet known if there will be 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
The collected identified for the primary outcome measure only will be shared.
When the data will become available and for how long
starting 12 months after publication
To whom data/document is available
En Available for people working in academic institutions
Under which criteria data/document could be used
En The data will provide for educational use
From where data/document is obtainable
Dr.mansour salesi mansour1380@yahoo.com
What processes are involved for a request to access data/document
En The data will send as soon as possible, after receiving the request