NAFLDPhase 2/3052920190055NCT04308980
Safety and Tolerability of Novel Medical Nutrition Products for NAFLD Treatment
A Phase 2/3 study testing Specialized product for medical nutrition (SPP-1) and individualized diet in people with NAFLD and NASH - Nonalcoholic Steatohepatitis, run by Russian Academy of Medical Sciences at 1 site in Russia.
Trial summary
To the moment, only limited data are present on the efficacy of changes in diet composition of patients with non-alcoholic fatty liver disease (NAFLD). The national database search in the federal registry of specialized products revealed no registered products for medical nutrition for patients with NAFLD. Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- NAFLD, NASH - Nonalcoholic Steatohepatitis
- What is being tested?
- Specialized product for medical nutrition (SPP-1) and individualized diet
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteRussia
- Study dates
- 20 Mar 2020to 31 Dec 2021
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males or females aged from 18 to 75 years inclusive;
- Willingness to participate based on the written informed consent form;
- Documented evidence of non-alcoholic fatty liver disease presence, defined based on the following: steatohepatitis evaluated by liver biopsy taken within 12 months prior to enrolment (when liver biopsy is available, at least a score of 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3), NAS ≥4, fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system should be present); or ultrasound markers of fatty liver in combination with persistent elevated alanine aminotransferase (ALT; absence of normal value of ALT within the past year), obesity defined by a body mass index (BMI) ≥30, metabolic syndrome (NCEP ATP III definition), type 2 diabetes, or homeostasis model assessment of insulin resistance (HOMA-IR) >6;
- Patients in whom it is safe and practical to proceed with specialized medical food product treatment;
- If a patient is treated with 1 of the following drugs: vitamin E (>400 IU/day), polyunsaturated fatty acids (>2 g/day), or ursodeoxycholic acid; a stable dose from at least 6 months prior to the enrolment;
- For patients with type 2 diabetes, glycaemia must be controlled. If glycaemia is controlled by antidiabetic drugs, change in anti-diabetic therapy must follow these requirements:
- no qualitative change 6 months prior to randomization (i.e., implementation of a new anti-diabetic therapy) for patients treated with metformin, gliptins, sulfonylureas, sodium/glucose cotransporter (SGLT) 2 inhibitors, glucagon-like peptide (GLP)-1 agonists, or insulin. Dose changes of these medications are allowed in the 6 months prior to randomization, except for GLP-1 agonists, which must remain on stable dose in the 12 months prior to enrolment.
- no implementation of any antidiabetic drugs before the end of the treatment (day 14).
Who cannot join
- Pregnant or breast feeding females;
- Liver cirrhosis based on liver histology or liver stiffness measurements (> or equal to 14 kPa), or APRI >or equal to 1; or BARD score > or equal to 2.
- Known chronic heart failure (Grade I to IV of New York Heart Association classification).
- History of efficient bariatric surgery within 5 years prior to enrollment.
- Uncontrolled hypertension during the Screening Period despite optimal antihypertensive therapy.
- Type 1 diabetes patients.
Show all 40Show fewer
- Patients with haemoglobin A1c [HbA1c] >9.0%.
- Patients with a history of clinically significant acute cardiac event within 6 months prior to Screening
- Weight loss of more than 5% within 6 months prior to Randomization.
- Current or recent history (<5 years) of significant alcohol consumption. For men, significant consumption is defined as higher than 30 g pure alcohol per day. For women, it is typically defined as higher than 20 g pure alcohol per day
- Other well documented causes of chronic liver disease according to standard diagnostic procedures including, but not limited to:
- positive hepatitis B surface antigen
- positive hepatitis C Virus (HCV) RNA (tested for in case of known cured HCV infection or positive HCV Ab at Screening)
- suspicion of drug-induced liver disease
- alcoholic liver disease
- autoimmune hepatitis
- Wilson's disease
- primary biliary cirrhosis, primary sclerosing cholangitis
- genetic homozygous haemochromatosis
- known or suspected hepatocellular carcinoma (HCC)
- history or planned liver transplant, or current MELD score >12
- Known hypersensitivity to the investigation product or any of its components.
- Patients who are currently participating in, plan to participate in, or have participated in an investigational drug trial or medical device trial containing active substance within 30 days or five half-lives, whichever is longer, prior to Screening.
- Use of the following concomitant medications:
- Fibrates are not permitted from 2 months before Randomization. Patients that used statins, ezetimibe, or other nonfibrate lipid lowering drugs before Screening may participate if the dosage has been kept constant for at least 2 months prior to Screening.
- Currently taking drugs that can induce steatosis/steatohepatitis including, but not restricted to: corticosteroids (parenteral \& oral chronic administration only), amiodarone (Cordarone), tamoxifen (Nolvadex), and methotrexate (Rheumatrex, Trexall), which are not permitted 30 days prior to Screening and up to end of treatment.
- Currently taking any medication that could interfere with study medication absorption, distribution, metabolism, or excretion or could lead to induction or inhibition of microsomal enzymes, e.g., indomethacin, which are not permitted from Randomization until end of treatment.
- Patients who have the following associated illnesses or conditions:
- Any medical conditions that may diminish life expectancy to less than 2 years including known cancers;
- Evidence of any other unstable or, untreated clinically significant immunological, endocrine, hematological, gastrointestinal, neurological, neoplastic, or psychiatric disease;
- Mental instability or incompetence, such that the validity of informed consent or ability to be compliant with the study is uncertain.
- patients should not present any of the following biological exclusion criteria:
- Positive anti-human immunodeficiency virus antibody.
- Aspartate aminotransferase (AST) and/or ALT >10 x upper limit of normal (ULN).
- Conjugated bilirubin > 26 umol/l due to altered hepatic function (Gilbert Disease patients are allowed into the study.
- International normalized ratio >1.40 due to altered hepatic function.
- Platelet count <100,000/mm^3 due to portal hypertension.
- Significant renal disease, including nephritic syndrome, chronic kidney disease (defined as patients with markers of kidney damage or estimated glomerular filtration rate [eGFR] of less than 60 ml/min/1.73 m^2).
- Patients for whom participation in the trial is not reasonable according to the opinion of Investigator or in cases when participation in the trial may put the patient at any kind of risk.
- The data of patients with evidence or suspected compliance to the provided treatment lower than 80% will be excluded from the analysis
Trial locations and contacts
1 site in 1 country.
Russia1 site, 1 recruiting
- Recruiting
Gastroenterology and Hepatology, FRC Nutrition and Biotechnology
Moscow, 115446
Sergey Morozov, MD, PhD, +74996131091, 84996131091@mail.ru
Armida Sasunova, MD, +74997943572, armida.sasunova@yandex.ru
About this study
Official title: Development and Evaluation of the Effectiveness of Complex Therapy of Steatohepatitis of Various Aetiologies Based on Metabolomic Analysis With the Use of Innovative Medical Nutrition Products
To the moment, only limited data are present on the efficacy of changes in diet composition of patients with non-alcoholic fatty liver disease (NAFLD). The national database search in the federal registry of specialized products revealed no registered products for medical nutrition for patients with NAFLD. We developed the composition of specialized food products, produced their experimental batches, and performed laboratory studies of their safety, including tests on toxicology and microbiology (which revealed no concerns). Organoleptic studies of the products showed acceptable results. The aim of the present study is to assess safety and tolerability of newly developed specialized products for medical nutrition of patients with non-alcoholic fatty liver diseases in a prospective randomized placebo-controlled trial.
Read the detailed description
Development of specialized medical products is actual due to the high prevalence of non-alcoholic fatty liver disease (NAFLD), which accounts for 20-30% of the world's population, while non-alcoholic steatohepatitis (NASH) accounts for about 20% of all cases of NAFLD and affects all age groups, including children. Currently, there are no generally accepted and efficient methods to treat the disease. Recommended measures include changes in lifestyle, i.e., weight loss and dietary modifications together with increased physical activity. Pragmatic approaches combining dietary restriction and a progressive increase in aerobic exercise / resistance training are preferable and should be individually tailored. Only general principles of diet modification are strongly recommended, though the evidence of their efficacy is far from excellent. According to EASL 2016 guidelines on NAFLD, there is a need for energy restriction, exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose; the macronutrient composition should be adjusted according to the Mediterranean diet) and avoidance of excessive alcohol intake. Only limited data are available on the change of diet composition, including the intake of products with low glycaemic index, containing larger amounts of components with known antioxidant capacity (including vitamins and minerals) and dietary fibre. Still, the use of mentioned components is promising in the regard of their potential to trigger metabolic changes, decrease insulin resistance, inflammatory processes in the liver tissue and excessive lipid accumulation in the liver in patients with NAFLD. The database search in the federal registry of specialized products revealed no specialized products for medical nutrition for patients with NAFLD. Despite some similarities in the pathogenesis of the diseases, specialized medical products for patients with diabetes mellitus are not optimal for patients with fatty liver disease. Based on the published data, medical and biological requirements for specialized product of medical nutrition were formulated. According to them, at an earlier stage of the present work we developed the composition of specialized food products, produced their experimental batches, and performed laboratory studies of their safety, including tests on toxicology and microbiology (which revealed no concerns). Organoleptic studies of the products showed acceptable results. The aim of the present study is to assess safety and tolerability of newly developed specialized products for medical nutrition of patients with non-alcoholic fatty liver diseases in a prospective randomized placebo-controlled trial.
- Conditions
- NAFLD, NASH - Nonalcoholic Steatohepatitis
- Being tested
- Specialized product for medical nutrition (SPP-1), individualized diet
- Keywords
- diet, nutrition, specialized food product, medical nutrition products, NAFLD, NASH, steatohepatitis
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Fatty Liver
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Specialized product for medical nutrition (SPP-1)Dietary supplement
Patients randomly allocated to this group will use specialized product for medical nutrition (SPP-1). This product contains: soy protein, whey protein concentrate, microcapsulated rapeseed oil, maltodextrin, inulin, Polydextrose, soy lecithin, potassium citrate, magnesium lactate, ω-3 PUFA (docosahexaenoic acid), sweetener mixture (stevia extract, erythritol), natural flavor "Yogurt-vanilla", calcium carbonate, betaine hydrochloride, natural flavor "raspberry", vitamin premix (vitamins a, e, C, D3, B1, B2, B6, B12, PP, folic acid, Pantothenic acid, K1, Biotin), beet juice concentrate, carrageenan, mineral premix (iron, zinc, copper, manganese, iodine, selenium, molybdenum, chromium), alpha-lipoic acid. The product is packed in approved by sanitary rules bags by 30 g. The instant drink obtained by the mixture of the bag content with warm (30-60C) water should be used immediately after being prepared. The daily dose is 1 pack TID
individualized dietBehavioural
All the patients enrolled to the study will be provided with recommendations on diet. Individualized requirements will be calculated based on the results of indirect calorimetry (resting energy expenditures) and measurements of urea in daily urine
| Study group | Role | What they receive |
|---|---|---|
| Active treatment | Experimental | Patients with verified non-alcoholic fatty liver disease, who signed informed consent to participate in the study and are randomly selected to use specialized medical nutrition product together with diet based on the measured individual requirements in energy and protein intake. Receives: Dietary Supplement: Specialized product for medical nutrition (SPP-1); Behavioral: individualized diet |
| Control group | Placebo comparator | Patients with verified non-alcoholic fatty liver disease, who signed informed consent to participate in the study and are randomly selected to use masked placebo together with diet based on the measured individual requirements in energy and protein intake. Receives: Behavioral: individualized diet |
What is being measured
The primary outcome is the main question the study is designed to answer.
Weight change
Assessment of weight before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of satiety level
Assessment of satiety will be performed before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of hunger level
Assessment of hunger will be performed with the use of the hunger scale before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Presence of adverse events
Assessment of adverse events will be performed before the start of treatment and along the period of treatment.
Measured: 14 days
Change of proportion of fat in body composition
Percent of fat in body composition will be assessed with bioelectrical impedance analysis (bioimpedance, BIA). The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of proportion of water in body composition
Percent of water in body composition will be assessed with BIA. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of lean body weight
Lean weight in body composition will be assessed with BIA. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change in blood docosahexaenoic acid concentration
High performance liquid chromatography with mass spectrometry analysis of blood samples will be performed to evaluate docosahexaenoic acid concentration before the start of medical food product intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change in blood hydroxyeycosatetraenoic acid concentration
High performance liquid chromatography with mass spectrometry analysis of blood samples will be performed to evaluate hydroxyeycosatetraenoic acid concentration before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Secondary outcomes (9)
Change of serum glucose concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum insulin concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum triglycerides concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum high-density lipoprotein concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum low-density lipoprotein concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum cholesterol concentration
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum gamma-glutamine transpeptidase (GGT) activity level
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum alanine amino-transferase (AST) activity level
Blood chemistry will be performed before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Change of serum alanine amino-transferase (ALT) activity
Blood (serum) ALT level will be measured before the start of the product/placebo intake and on the last (14th) day of treatment by blood chemistry. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Mar 2020
- Study start20 Mar 2020
- Primary completion1 Dec 2021 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for NAFLDStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Russian Academy of Medical Sciences
- Sponsor type
- University, hospital or other
- Collaborators
- Federal State Budgetary Scientific Institution
- Responsible party
- Principal investigator, Vasily Isakov, Russian Academy of Medical Sciences
- Investigators
- Vasily Isakov, Professor, Study chair, FRC Nutrition and Biotechnology
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04308980
- Sponsor's protocol ID
- АААА-А19-119032590090-7/6
- Acronym
- 052920190055
- Status last verified
- Feb 2021
- First submitted
- 12 Mar 2020
- Last updated
- 3 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Blinded IPD data may be available upon request after the study is complete
Publications
European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.
PubMed 27062661Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
PubMed 21623852Barrera F, George J. The role of diet and nutritional intervention for the management of patients with NAFLD. Clin Liver Dis. 2014 Feb;18(1):91-112. doi: 10.1016/j.cld.2013.09.009. Epub 2013 Oct 24.
PubMed 24274867Zelber-Sagi S, Ratziu V, Oren R. Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World J Gastroenterol. 2011 Aug 7;17(29):3377-89. doi: 10.3748/wjg.v17.i29.3377.
PubMed 21876630Arab JP, Candia R, Zapata R, Munoz C, Arancibia JP, Poniachik J, Soza A, Fuster F, Brahm J, Sanhueza E, Contreras J, Cuellar MC, Arrese M, Riquelme A. Management of nonalcoholic fatty liver disease: an evidence-based clinical practice review. World J Gastroenterol. 2014 Sep 14;20(34):12182-201. doi: 10.3748/wjg.v20.i34.12182.
PubMed 25232252Boden G. High- or low-carbohydrate diets: which is better for weight loss, insulin resistance, and fatty livers? Gastroenterology. 2009 May;136(5):1490-2. doi: 10.1053/j.gastro.2009.03.019. Epub 2009 Mar 21. No abstract available.
PubMed 19318102Argo CK, Patrie JT, Lackner C, Henry TD, de Lange EE, Weltman AL, Shah NL, Al-Osaimi AM, Pramoonjago P, Jayakumar S, Binder LP, Simmons-Egolf WD, Burks SG, Bao Y, Taylor AG, Rodriguez J, Caldwell SH. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol. 2015 Jan;62(1):190-7. doi: 10.1016/j.jhep.2014.08.036. Epub 2014 Sep 6.
PubMed 25195547Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O'Dea K, Desmond PV, Johnson NA, Wilson AM. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013 Jul;59(1):138-43. doi: 10.1016/j.jhep.2013.02.012. Epub 2013 Feb 26.
PubMed 23485520Sasunova AN, Morozov SV, Sobolev RV, Isakov VA, Kochetkova AA, Vorobyeva IS. [Efficacy of newly developed food for special dietary use in the diet of patients with non-alcoholic steatohepatitis]. Vopr Pitan. 2022;91(2):31-42. doi: 10.33029/0042-8833-2022-91-2-31-42. Epub 2022 Mar 14. Russian.
PubMed 35596633
Study at a glance
From the registry record, last updated by the sponsor on 3 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Development and Evaluation of the Effectiveness of Complex Therapy of Steatohepatitis of Various Aetiologies Based on Metabolomic Analysis With the Use of Innovative Medical Nutrition Products
- ClinicalTrials.gov ID
- NCT04308980
- Acronym / sponsor ID
- 052920190055 / АААА-А19-119032590090-7/6
- Conditions
- NAFLD, NASH - Nonalcoholic Steatohepatitis
- Keywords
- diet, nutrition, specialized food product, medical nutrition products, NAFLD, NASH, steatohepatitis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 45 participants (estimated)
- Lead sponsor
- Russian Academy of Medical SciencesUniversity, hospital or other
- Collaborators
- Federal State Budgetary Scientific Institution
- Study start
- 20 Mar 2020 (actual)
- Primary completion
- 1 Dec 2021 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 16 Mar 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
To the moment, only limited data are present on the efficacy of changes in diet composition of patients with non-alcoholic fatty liver disease (NAFLD). The national database search in the federal registry of specialized products revealed no registered products for medical nutrition for patients with NAFLD. We developed the composition of specialized food products, produced their experimental batches, and performed laboratory studies of their safety, including tests on toxicology and microbiology (which revealed no concerns). Organoleptic studies of the products showed acceptable results. The aim of the present study is to assess safety and tolerability of newly developed specialized products for medical nutrition of patients with non-alcoholic fatty liver diseases in a prospective randomized placebo-controlled trial.
Detailed description
Development of specialized medical products is actual due to the high prevalence of non-alcoholic fatty liver disease (NAFLD), which accounts for 20-30% of the world's population, while non-alcoholic steatohepatitis (NASH) accounts for about 20% of all cases of NAFLD and affects all age groups, including children. Currently, there are no generally accepted and efficient methods to treat the disease. Recommended measures include changes in lifestyle, i.e., weight loss and dietary modifications together with increased physical activity. Pragmatic approaches combining dietary restriction and a progressive increase in aerobic exercise / resistance training are preferable and should be individually tailored. Only general principles of diet modification are strongly recommended, though the evidence of their efficacy is far from excellent. According to EASL 2016 guidelines on NAFLD, there is a need for energy restriction, exclusion of NAFLD-promoting components (processed food, and food and beverages high in added fructose; the macronutrient composition should be adjusted according to the Mediterranean diet) and avoidance of excessive alcohol intake. Only limited data are available on the change of diet composition, including the intake of products with low glycaemic index, containing larger amounts of components with known antioxidant capacity (including vitamins and minerals) and dietary fibre. Still, the use of mentioned components is promising in the regard of their potential to trigger metabolic changes, decrease insulin resistance, inflammatory processes in the liver tissue and excessive lipid accumulation in the liver in patients with NAFLD. The database search in the federal registry of specialized products revealed no specialized products for medical nutrition for patients with NAFLD. Despite some similarities in the pathogenesis of the diseases, specialized medical products for patients with diabetes mellitus are not optimal for patients with fatty liver disease. Based on the published data, medical and biological requirements for specialized product of medical nutrition were formulated. According to them, at an earlier stage of the present work we developed the composition of specialized food products, produced their experimental batches, and performed laboratory studies of their safety, including tests on toxicology and microbiology (which revealed no concerns). Organoleptic studies of the products showed acceptable results. The aim of the present study is to assess safety and tolerability of newly developed specialized products for medical nutrition of patients with non-alcoholic fatty liver diseases in a prospective randomized placebo-controlled trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Active treatment | Experimental | Dietary Supplement: Specialized product for medical nutrition (SPP-1), Behavioral: individualized dietPatients with verified non-alcoholic fatty liver disease, who signed informed consent to participate in the study and are randomly selected to use specialized medical nutrition product together with diet based on the measured individual requirements in energy and protein intake. |
| Control group | Placebo comparator | Behavioral: individualized dietPatients with verified non-alcoholic fatty liver disease, who signed informed consent to participate in the study and are randomly selected to use masked placebo together with diet based on the measured individual requirements in energy and protein intake. |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Males or females aged from 18 to 75 years inclusive;
- Willingness to participate based on the written informed consent form;
- Documented evidence of non-alcoholic fatty liver disease presence, defined based on the following: steatohepatitis evaluated by liver biopsy taken within 12 months prior to enrolment (when liver biopsy is available, at least a score of 1 in each component of the NAS (steatosis scored 0-3, ballooning degeneration scored 0-2, and lobular inflammation scored 0-3), NAS ≥4, fibrosis stage of 1 or greater and below 4, according to the NASH CRN fibrosis staging system should be present); or ultrasound markers of fatty liver in combination with persistent elevated alanine aminotransferase (ALT; absence of normal value of ALT within the past year), obesity defined by a body mass index (BMI) ≥30, metabolic syndrome (NCEP ATP III definition), type 2 diabetes, or homeostasis model assessment of insulin resistance (HOMA-IR) >6;
- Patients in whom it is safe and practical to proceed with specialized medical food product treatment;
- If a patient is treated with 1 of the following drugs: vitamin E (>400 IU/day), polyunsaturated fatty acids (>2 g/day), or ursodeoxycholic acid; a stable dose from at least 6 months prior to the enrolment;
Key exclusion criteria (40 listed)
- Pregnant or breast feeding females;
- Liver cirrhosis based on liver histology or liver stiffness measurements (> or equal to 14 kPa), or APRI >or equal to 1; or BARD score > or equal to 2.
- Known chronic heart failure (Grade I to IV of New York Heart Association classification).
- History of efficient bariatric surgery within 5 years prior to enrollment.
- Uncontrolled hypertension during the Screening Period despite optimal antihypertensive therapy.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Specialized product for medical nutrition (SPP-1)Patients randomly allocated to this group will use specialized product for medical nutrition (SPP-1). This product contains: soy protein, whey protein concentrate, microcapsulated rapeseed oil, maltodextrin, inulin, Polydextrose, soy lecithin, potassium citrate, magnesium lactate, ω-3 PUFA (docosahexaenoic acid), sweetener mixture (stevia extract, erythritol), natural flavor "Yogurt-vanilla", calcium carbonate, betaine hydrochloride, natural flavor "raspberry", vitamin premix (vitamins a, e, C, D3, B1, B2, B6, B12, PP, folic acid, Pantothenic acid, K1, Biotin), beet juice concentrate, carrageenan, mineral premix (iron, zinc, copper, manganese, iodine, selenium, molybdenum, chromium), alpha-lipoic acid. The product is packed in approved by sanitary rules bags by 30 g. The instant drink obtained by the mixture of the bag content with warm (30-60C) water should be used immediately after being prepared. The daily dose is 1 pack TID | Dietary supplement | Active treatment |
| individualized dietAll the patients enrolled to the study will be provided with recommendations on diet. Individualized requirements will be calculated based on the results of indirect calorimetry (resting energy expenditures) and measurements of urea in daily urine | Behavioural | Active treatment, Control group |
Primary outcome
Weight change
Time frame: 14 days
Assessment of weight before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Change of satiety level
Time frame: 14 days
Assessment of satiety will be performed before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Change of hunger level
Time frame: 14 days
Assessment of hunger will be performed with the use of the hunger scale before the start of treatment and on the 14th day of treatment. Change will be calculated as a difference from the subtraction of the second measurement from the first.
Presence of adverse events
Time frame: 14 days
Assessment of adverse events will be performed before the start of treatment and along the period of treatment.
Change of proportion of fat in body composition
Time frame: 14 days
Percent of fat in body composition will be assessed with bioelectrical impedance analysis (bioimpedance, BIA). The change will be calculated as a difference from the subtraction of the second measurement from the first.
Change of proportion of water in body composition
Time frame: 14 days
Percent of water in body composition will be assessed with BIA. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Change of lean body weight
Time frame: 14 days
Lean weight in body composition will be assessed with BIA. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Change in blood docosahexaenoic acid concentration
Time frame: 14 days
High performance liquid chromatography with mass spectrometry analysis of blood samples will be performed to evaluate docosahexaenoic acid concentration before the start of medical food product intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
Change in blood hydroxyeycosatetraenoic acid concentration
Time frame: 14 days
High performance liquid chromatography with mass spectrometry analysis of blood samples will be performed to evaluate hydroxyeycosatetraenoic acid concentration before the start of medical food product/placebo intake and on the last (14th) day of treatment. The change will be calculated as a difference from the subtraction of the second measurement from the first.
9 secondary outcomes
Change of serum glucose concentration
Time frame: 14 days
Change of serum insulin concentration
Time frame: 14 days
Change of serum triglycerides concentration
Time frame: 14 days
Change of serum high-density lipoprotein concentration
Time frame: 14 days
Change of serum low-density lipoprotein concentration
Time frame: 14 days
Change of serum cholesterol concentration
Time frame: 14 days
Change of serum gamma-glutamine transpeptidase (GGT) activity level
Time frame: 14 days
Change of serum alanine amino-transferase (AST) activity level
Time frame: 14 days
Change of serum alanine amino-transferase (ALT) activity
Time frame: 14 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Feb 2021.
- Background: PubMed 27062661European Association for the Study of the Liver (EASL); European Association for the Study of Diabetes (EASD); European Association for the Study of Obesity (EASO). EASL-EASD-EASO Clinical Practice Guidelines for the management of non-alcoholic fatty liver disease. J Hepatol. 2016 Jun;64(6):1388-402. doi: 10.1016/j.jhep.2015.11.004. Epub 2016 Apr 7. No abstract available.
- Background: PubMed 21623852Vernon G, Baranova A, Younossi ZM. Systematic review: the epidemiology and natural history of non-alcoholic fatty liver disease and non-alcoholic steatohepatitis in adults. Aliment Pharmacol Ther. 2011 Aug;34(3):274-85. doi: 10.1111/j.1365-2036.2011.04724.x. Epub 2011 May 30.
- Background: PubMed 24274867Barrera F, George J. The role of diet and nutritional intervention for the management of patients with NAFLD. Clin Liver Dis. 2014 Feb;18(1):91-112. doi: 10.1016/j.cld.2013.09.009. Epub 2013 Oct 24.
- Background: PubMed 21876630Zelber-Sagi S, Ratziu V, Oren R. Nutrition and physical activity in NAFLD: an overview of the epidemiological evidence. World J Gastroenterol. 2011 Aug 7;17(29):3377-89. doi: 10.3748/wjg.v17.i29.3377.
- Background: PubMed 25232252Arab JP, Candia R, Zapata R, Munoz C, Arancibia JP, Poniachik J, Soza A, Fuster F, Brahm J, Sanhueza E, Contreras J, Cuellar MC, Arrese M, Riquelme A. Management of nonalcoholic fatty liver disease: an evidence-based clinical practice review. World J Gastroenterol. 2014 Sep 14;20(34):12182-201. doi: 10.3748/wjg.v20.i34.12182.
- Background: PubMed 19318102Boden G. High- or low-carbohydrate diets: which is better for weight loss, insulin resistance, and fatty livers? Gastroenterology. 2009 May;136(5):1490-2. doi: 10.1053/j.gastro.2009.03.019. Epub 2009 Mar 21. No abstract available.
- Background: PubMed 25195547Argo CK, Patrie JT, Lackner C, Henry TD, de Lange EE, Weltman AL, Shah NL, Al-Osaimi AM, Pramoonjago P, Jayakumar S, Binder LP, Simmons-Egolf WD, Burks SG, Bao Y, Taylor AG, Rodriguez J, Caldwell SH. Effects of n-3 fish oil on metabolic and histological parameters in NASH: a double-blind, randomized, placebo-controlled trial. J Hepatol. 2015 Jan;62(1):190-7. doi: 10.1016/j.jhep.2014.08.036. Epub 2014 Sep 6.
- Background: PubMed 23485520Ryan MC, Itsiopoulos C, Thodis T, Ward G, Trost N, Hofferberth S, O'Dea K, Desmond PV, Johnson NA, Wilson AM. The Mediterranean diet improves hepatic steatosis and insulin sensitivity in individuals with non-alcoholic fatty liver disease. J Hepatol. 2013 Jul;59(1):138-43. doi: 10.1016/j.jhep.2013.02.012. Epub 2013 Feb 26.
- Derived from this study: PubMed 35596633Sasunova AN, Morozov SV, Sobolev RV, Isakov VA, Kochetkova AA, Vorobyeva IS. [Efficacy of newly developed food for special dietary use in the diet of patients with non-alcoholic steatohepatitis]. Vopr Pitan. 2022;91(2):31-42. doi: 10.33029/0042-8833-2022-91-2-31-42. Epub 2022 Mar 14. Russian.
- Information about institution where the study is performedLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Blinded IPD data may be available upon request after the study is complete
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Vasily Isakov, Professor study chair
FRC Nutrition and Biotechnology
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Specialized product for medical nutrition (SPP-1) and individualized diet in people with NAFLD and NASH - Nonalcoholic Steatohepatitis, run by Russian Academy of Medical Sciences at 1 site in Russia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 40 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Russia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sergey Morozov, MD, PhD (+79104681801, 84996131091@mail.ru), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Weight change (time frame: 14 days). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04308980, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Feb 2021.