Safety and Tolerability of Novel Medical Nutrition Products for NAFLD Treatment

NCT04308980 | Unknown Phase 2 DMC

• 1 other identifier: АААА-А19-119032590090-7/6
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief 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. 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

Keywords

diet; nutrition; specialized food product; medical nutrition products; NAFLD; NASH; steatohepatitis

Outcome Measures

Primary Outcomes (9)

• 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.

  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.

  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.

  14 days

• Presence of adverse events

  Assessment of adverse events will be performed before the start of treatment and along the period of treatment.

  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.

  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.

  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.

  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.

  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.

  14 days

Secondary Outcomes (9)

• Change of serum glucose concentration

  14 days

• Change of serum insulin concentration

  14 days

• Change of serum triglycerides concentration

  14 days

• Change of serum high-density lipoprotein concentration

  14 days

• Change of serum low-density lipoprotein concentration

  14 days

Other Outcomes (1)

• Change in concentration of volatile compounds in stool samples

  14 days

Study Arms (2)

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.

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.

Behavioral: individualized diet

Interventions

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

Active treatment

individualized diet BEHAVIORAL

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

Active treatment; Control group

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Russian Academy of Medical Sciences: lead
• Federal State Budgetary Scientific Institution "Federal Research Centre of Nutrition, Biotechnology: collaborator

Study Sites (1)

Gastroenterology and Hepatology, FRC Nutrition and Biotechnology

Moscow, 115446, Russia

RECRUITING

Related Publications (9)

• 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.

  PMID: 27062661 BACKGROUND

• Vernon 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.

  PMID: 21623852 BACKGROUND

• Barrera 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.

  PMID: 24274867 BACKGROUND

• Zelber-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.

  PMID: 21876630 BACKGROUND

• Arab 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.

  PMID: 25232252 BACKGROUND

• Boden 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.

  PMID: 19318102 BACKGROUND

• Argo 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.

  PMID: 25195547 BACKGROUND

• Ryan 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.

  PMID: 23485520 BACKGROUND

• Sasunova 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.

  PMID: 35596633 DERIVED

Related Links

• Information about global research project
• Information about institution where the study is performed

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Fatty Liver

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases

Study Officials

• Vasily Isakov, Professor

  FRC Nutrition and Biotechnology

  STUDY CHAIR

Central Study Contacts

Sergey Morozov, MD, PhD

CONTACT

+79104681801; 84996131091@mail.ru

Armida Sasunova, MD

CONTACT

+79197718525; armida.sasunova@yandex.ru

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 16, 2020
• Study Start: March 20, 2020
• Primary Completion: December 1, 2021
• Study Completion: December 31, 2021
• Last Updated: February 3, 2021

Record last verified: 2021-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: After study completion within 2 years
• Access Criteria: Upon request

Locations

RU (1)