Effect of PNPLA3, TM6SF2 and MBOAT7 Genetic Variants on Non-alcoholic Fatty Liver Disease Therapeutic Outcome.

NCT04640324 | Completed DMC

• 1 other identifier: 531/2016
• Study Type: interventional
• Target: 92
• Locations: 1 country
• Sites: 3

Brief Summary

Patatin-like phospholipase domain-containing protein-3 (PNPLA3), the transmembrane 6 superfamily member 2 protein (TM6SF2) and membrane bound O-acyltransferase domain containing 7 (MBOAT7) genes are involved in non-alcoholic fatty liver disease (NAFLD) development and worsening. Following the actual scientific knowledge, some studies have identified the genetic background surrounding NAFLD, counting up to forty different genetic variants that seem to exert also a crucial role in the disease evolution, according to the natural history, until hepatocellular carcinoma onset. However, few data exist regarding their influence on the treatment response. The aim was to explore the effect of 303 mg of silybin-phospholipids complex, 10 mg of vitamin-D and 15 mg of vitamin-E twice a day for six months in NAFLD patients carrying PNPLA3-rs738409, TM6SF2-rs58542926 and MBOAT7-rs641738 genetic variants. The assessed mutations are independently associated with no response to a silybin/vitamin D-based therapy and could be useful therapeutic predictive markers in this context.

Conditions

Non-Alcoholic Fatty Liver Disease; Insulin Resistance

Keywords

non-alcoholic fat ty liver disease; genetics; insulin resistance; nutraceutics

Outcome Measures

Primary Outcomes (1)

• Number of participants in each study group which shown an improvement from baseline of insulin resistance assed by HOMA-IR

  The HOMA-IR was calculated using the following formula: fasting insulin (μU/mL) × plasma glucose (mmol/L)/22.5. The investigators considered the patients responder if at least one of the following criteria was addressed: normalization of the HOMA-IR (\<2.5) at the end of treatment starting from baseline values greater than 2.5; reduction of the HOMA-IR ≥ 2 points at the end of treatment in comparison to baseline.

  Six months

Secondary Outcomes (4)

• Mean change in ALT levels from baseline

  Six months

• Mean change in insulin levels from baseline

  Six months

• Mean change in CRP levels from baseline

  Six months

• Mean change in TBARS levels from baseline

  Six months

Study Arms (3)

NAFLD wild type control group

NO INTERVENTION

Consisted of not treated NAFLD wild type patients

NAFLD wild type treated group

ACTIVE COMPARATOR

Consisted of NAFLD wild type patients treated with oral administration of 303mg of silybin-phospholipid complex, 10mg of vitamin D, and 15mg of vitamin E, twice a day six months

Drug: Nutraceutical therapy

NAFLD mutated treated group

EXPERIMENTAL

Consisted of NAFLD patients carrying at least one mutation among PNPLA3, TM6SF2, MBOAT7 genes, treated with oral administration of 303mg of silybin-phospholipid complex, 10mg of vitamin D, and 15mg of vitamin E, twice a day six months

Drug: Nutraceutical therapy

Interventions

Nutraceutical therapy DRUG

Oral administration of 303mg of silybin-phospholipid complex, 10mg of vitamin D, and 15mg of vitamin E, twice a day for six months

Also known as: Silybin-phospholipid, Vitamin D and vitamin E complex

NAFLD mutated treated group; NAFLD wild type treated group

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• age between 18 and 80 years
• diagnosis of NAFLD

You may not qualify if:

• diagnosis of chronic inflammatory disease such as inflammatory bowel disease, rheumatoid arthritis, acute or chronic kidney disease, systemic lupus erythematosus, or other major inflammatory systemic diseases
• diagnosis of insulin dependent diabetes
• diagnosis of tumors
• diagnosis of ongoing infections
• alcohol or drug abuse medical history
• diagnosis of other etiologies of chronic liver damage
• use of hepatoprotective drugs
• psychological/psychiatric problems that could invalidate the informed consent

Sponsors & Collaborators

• University of Campania Luigi Vanvitelli: lead
• Federico II University: collaborator
• University of Salerno: collaborator

Study Sites (3)

University of Salerno

Fisciano, Salerno, 84084, Italy

Location

University of Campania "Luigi Vanvitelli"

Naples, 80131, Italy

Location

University of Naples "Federico II)

Naples, 80138, Italy

Location

Related Publications (23)

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• Dallio M, Masarone M, Romeo M, Tuccillo C, Morisco F, Persico M, Loguercio C, Federico A. PNPLA3, TM6SF2, and MBOAT7 Influence on Nutraceutical Therapy Response for Non-alcoholic Fatty Liver Disease: A Randomized Controlled Trial. Front Med (Lausanne). 2021 Oct 8;8:734847. doi: 10.3389/fmed.2021.734847. eCollection 2021.

  PMID: 34692725 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Insulin Resistance

Interventions

Vitamin D

Condition Hierarchy (Ancestors)

Fatty Liver; Liver Diseases; Digestive System Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Secosteroids; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Alessandro Federico, Professor

  University of Campania Luigi Vanvitelli

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: The 92 enrolled patients were divided in three groups: NAFLD wild type control group (n. 30), NAFLD treated wild type group (n. 30), NAFLD treated mutated group (n. 32). The block randomization method was used to randomize the 60 not mutated patients in the NAFLD wild-type control group and NAFLD treated wild type one. The patients inserted in the NAFLD treated wild type and NAFLD treated mutated groups were undergone to an oral administration of 303mg of silybin-phospholipid complex, 10mg of vitamin D, and 15mg of vitamin E, twice a day for six months. At the baseline and end of treatment, the assessment of WHtR, blood pressure measurement, BMI, Blood glucose and insulin, HOMA-IR, AST, ALT, GGT, blood count, CRP, TBARS, liver stiffness and CAP was performed. During the experimental observation, patients were on free diet on the basis of dietary habits before the enrollment and any type of physical exercise was recommended during the study period.

Study Record Dates

• First Submitted: November 17, 2020
• First Posted: November 23, 2020
• Study Start: January 16, 2017
• Primary Completion: October 17, 2017
• Study Completion: April 17, 2018
• Last Updated: November 24, 2020

Record last verified: 2020-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: Starting 6 months after publication for 10 years
• Access Criteria: All the data that support the results of the publication will be shared upon reasonable request by correspondence to alessandro.federico@unicampania.it or marcello.dallio@unicampania.it

Locations

IT (3)