Protocol summary
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Study aim
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Determining the effect myo-inositol supplementation on nutritional status, cardiometabolic factors, liver function, oxidative stress, visfatin and hs-CRP levels, gene expression of insulin resistance pathway and HIF1α, NF-kB, TNF-α, Interleukin-1β and 6 in patients with non-alcoholic fatty liver disease
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Design
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Double-blinded placebo-controlled RCT on 50 patients
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Settings and conduct
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Individuals were randomly allocated into myo-inositol or placebo groups. The duration of the trial will be 8 weeks .At the beginning of the study, both groups will be given nutritional recommendations.
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Participants/Inclusion and exclusion criteria
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Inclusion criteria:
patients with NAFLD (grade 1 and 2)
both sexes
age 18-55 years
BMI between 30-40 kg/m2
exclusion criteria:
Athlete, pregnancy, lactation and menopause
use of birth control pills and estrogen
Smoking and alcohol use
special diet
Use of medicines for weight loss
Taking medications affecting liver function for 3 months before or during the study
Diseases with similar pathogenesis
Intention of getting pregnant
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Intervention groups
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The intervention group will take myo-inositol supplement ( 2 gram sachets of myo-inositol before lunch and dinner) and placebo group (2 gram sachets of maltodextrin before lunch and dinner) for 8 weeks. At the beginning of the study, both groups will be given Nutritional recommendations.
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Main outcome variables
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Nutritional status (energy, macronutrients, micronutrients intake), Cardiometabolic status (glucose-insulin-HbA1c-HOMA-IR score)- (TG-TC-HDL-C-LDL-C)-SBP,DBP) Oxidative status (GPx ، SOD ، MDA ، CAT, NO, PON1 aryl esterase activity,TAC), visfatin and hs-CRP levels, Expression of inflammatory and insulin resistance genes, anthropometric indices (weight, BMI ,WC, WHR, WHtR)- body composition (Amount and % of body FM, FFM), liver function (liver ultrasonography and enzyme levels of ALT, AST and liver fibrosis score
General information
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Reason for update
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due to the addition of some variables to the previously approved protocol as well as changes in the title, we request to update this protocol.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT20100209003320N22
Registration date:
2021-10-04, 1400/07/12
Registration timing:
prospective
Last update:
2023-05-17, 1402/02/27
Update count:
1
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Registration date
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2021-10-04, 1400/07/12
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Expected recruitment start date
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2021-10-23, 1400/08/01
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Expected recruitment end date
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2022-04-21, 1401/02/01
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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The effect of myo-inositol supplementation on nutritional status, cardiometabolic factors, liver function, oxidative stress, visfatin and hs-CRP levels, gene expression of insulin resistance pathway and HIF1α, NF-kB, TNF-α, Interleukin-1β and 6 in patients with non-alcoholic fatty liver disease.
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Public title
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The effect of myo-inositol supplementation on NAFLD
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Age 18-55 years
Body mass index in the range of 30-40 Kg / m2
Willingness to cooperate
Hepatic steatosis based on Grade 1 and 2 NAFLD disease
Exclusion criteria:
Athlete, pregnancy, lactation and menopause in women
Infertility treatment, taking oral contraceptive pills
Smoking and alcohol use
Adherence to a special diet 3 months before the study
Use of chemical or herbal medicines for weight loss and use of hepatotoxic drugs such as phenytoin, amoxifine , lithium and antihypertensive drugs and lipid-lowering drugs (statins), insulin sensitiser medications
Taking antibiotics or dietary supplements that affect the levels of liver enzymes
History of weight loss surgery over the last year or rigid weight loss diets three months before the trial
Use of corticosteroids and NSAIDs or any type of supplements for 3 months before or during the study
Use of any multivitamin (vitamin E and folic acid, etc.), antioxidants (L-arginine, glutamine) and fish oil supplements for 3 months before or during the study
those with cardiovascular disease, hepatic, renal, intestinal, thyroid and parathyroid dysfunction, billiary disease, known autoimmune diseases, PCOs, cancers and conditions with mal-absorption such as Sprue and Crohn
Having symptoms of a recent infectious, inflammatory disease or recent surgery
Candidate or history of Liver transplant
Intention for pregnancy
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Age
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From 18 years old to 55 years old
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Gender
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Both
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Phase
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3
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Groups that have been masked
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Sample size
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Target sample size:
50
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Randomization (investigator's opinion)
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Randomized
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Randomization description
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A research assistant not otherwise involved in the study,
will be randomly allocated 50 patients into one of the two
experimental groups (1:1), using the Random allocation
software (RAS) and randomized block procedure of size
3 (age (18-30 vs 31-50 years)- gender (female vs male) and BMI
(<35 kg/m2 vs. ≥35 kg/m2)).
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Blinding (investigator's opinion)
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Double blinded
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Blinding description
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The person in charge of packaging myo-inositol and placebo supplements without knowing the content will determine the type of supplement or placebo that has no role in the implementation and analysis of the study data. None of the researchers or patients will be aware of the type of combination each person is receiving.
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Placebo
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Used
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Assignment
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Parallel
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Other design features
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Patients in both placebo and supplement groups will receive nutritional recommendations .
Ethics committees
1
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Ethics committee
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Approval date
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2021-09-13, 1400/06/22
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Ethics committee reference number
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IR.TBZMED.REC.1400.567
Health conditions studied
1
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Description of health condition studied
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non-alcoholic fatty liver
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ICD-10 code
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K76.0
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ICD-10 code description
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Fatty (change of) liver, not elsewhere classified
Primary outcomes
1
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Description
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Insulin
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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ELISA method
2
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Description
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HbA1C
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Chromatography
3
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Description
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Total cholesterol
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Enzymatic-colorimetric method using spectrophotometer
4
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Description
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Triglyceride
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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enzymatic-colorimetric method using spectrophotometer
5
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Description
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HDL-C
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Enzymatic-colorimetric method using spectrophotometer
6
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Description
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LDL-C
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
7
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Description
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HOMA-IR
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
8
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Description
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Superoxide dismutase (SOD)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
9
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Description
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Malondialdehyde (MDA)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
10
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Description
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Total Antioxidant Capacity (TAC)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
11
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Description
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Glutathione peroxidase(GPX)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
12
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Description
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Nitric oxide (NO)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
13
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Description
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Catalase (CAT)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
14
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Description
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paraoxonase arylesterase - 1 (PON-1)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Spectrophotometric method
15
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Description
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HIF1α gene expression
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
16
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Description
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Nuclear factor kappa-B (NF-kB) gene expression
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
17
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Description
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Tumor necrosis factor alpha (TNF-α) gene expression
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
18
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Description
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Interleukin-1-beta gene expression
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
19
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Description
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Interleukin 6 gene expression
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
20
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Description
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Body mass index (BMI)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
21
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Description
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Waist circumference
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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measuring tape
22
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Description
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waist-to-hip ratio (WHR)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
23
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Description
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Waist to Height Ratio (WHtR)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
24
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Description
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Fat mass
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Using bioelectric impedance analyzer
25
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Description
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Fat Free mass
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Using bioelectric impedance analyzer
26
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Description
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Energy, macronutrients and micronutrients intakes
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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a 3-days 24 hour- recall questionnaire at each phase will be completed and analyzed using Nutritionist 4 software
27
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Description
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Physical activity level
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Via short form of IPAQ questionnaire
28
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Description
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Appetite status
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Validated appetite questionnaire
29
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Description
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Weight
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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using Seca scale
30
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Description
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Serum albumin
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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using BROMOCRESOL GREEN
31
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Description
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Platelets count
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Using Coulter counter
32
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Description
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AMPK gene expression
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Timepoint
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Baseline and 8 weeks after the intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
33
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Description
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PDK gene expression
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Timepoint
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Baseline and 8 weeks after the intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
34
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Description
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AKT gene expression
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Timepoint
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Baseline and 8 weeks after the intervention
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Method of measurement
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Real-time polymerase chain reaction (RT-PCR)
35
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Description
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Visfatin
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Timepoint
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Baseline and 8 weeks after the intervention
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Method of measurement
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ELISA method
36
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Description
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hs-CRP
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Timepoint
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Baseline and 8 weeks after the intervention
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Method of measurement
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ELISA method
Secondary outcomes
1
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Description
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Fatty liver grade
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Ultrasonigraphy
2
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Description
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NAFLD fibrosis score
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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According to the formula
3
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Description
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Alanine aminotransferase (ALT)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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enzymatic method
4
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Description
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Aspartate aminotransferase (AST)
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Timepoint
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Baseline and 8 weeks after intervention
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Method of measurement
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Enzymatic method
Intervention groups
1
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Description
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Intervention group: Patients in this group will receive myo-inositol supplement and nutritional recommendation for 8 weeks. The supplement is: Sachet contains 2 grams of myo-inositol powder dissolved in a glass of water and consumed twice a day 30 minutes before lunch and dinner.
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Category
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Treatment - Drugs
2
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Description
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Control group: Patients in this group will receive placebo and nutritional recommendations for 8 weeks. The placebo is: A sachet containing 2 grams of maltodextrin powder which will be dissolved in a glass of water and consumed twice a day 30 minutes before lunch and dinner.
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Category
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Placebo
1
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Sponsor
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Grant name
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Grant code / Reference number
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Tabriz University of Medical Sciences
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Proportion provided by this source
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100
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Yes - There is a plan to make this available
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Study Protocol
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Yes - There is a plan to make this available
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Statistical Analysis Plan
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Yes - There is a plan to make this available
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Informed Consent Form
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Yes - There is a plan to make this available
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Clinical Study Report
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Yes - There is a plan to make this available
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Analytic Code
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Yes - There is a plan to make this available
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Data Dictionary
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Yes - There is a plan to make this available
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Title and more details about the data/document
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Data collected for the primary outcomes will be shared
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When the data will become available and for how long
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Access starting 12 months after publication
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To whom data/document is available
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The data will only be available for people working in academic institutions.
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Under which criteria data/document could be used
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The data of the present study will only be accessible by other researchers , for conducting meta-analysis
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From where data/document is obtainable
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Ms.Sara َArefhosseini, E-mail address:arefhosseini.sa@gmail.com, cellphone number: 09354720098 and Somaye Rostami E-mail address:somyrostammi96@gmail.com, cellphone number:09142399475
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What processes are involved for a request to access data/document
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The applicant should provide a brief description of the aims and methods of 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
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Comments
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