Bergamot and Cardoon extract for liver disease

ISRCTN	ISRCTN12833814
DOI	https://doi.org/10.1186/ISRCTN12833814
Secondary identifying numbers	219/2018/CE

Submission date: 05/08/2019
Registration date: 07/08/2019
Last edited: 06/09/2023

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Background and study aims
Non-alcoholic fatty liver disease is the most common cause of liver-related morbidity and mortality in the world. However, no effective drug treatment for this condition has been found. Oxidative stress is one of the key mediators of liver damage and represents a major contributor to the progression from simple steatosis to cirrhosis. It has been demonstrated that Bergamot (Citrus bergamia Risso et Poiteau) flavonoids decrease liver inflammation. Wild cardoon (Cynara cardunculus L.), is rich in antioxidant compounds which possess anti-inflammatory properties. The aim of this study is to test the effect of a new nutraceutical containing natural bioactive components from Bergamot and wild Cardoon, with antioxidant proprieties, as a treatment for patients with liver steatosis.

Who can participate?
Patients aged 30 and over with liver steatosis

What does the study involve?
Participants are randomly allocated to the intervention group or the control group. The intervention group receive Bergacyn®, containing a Bergamot polyphenol fraction and Cynara Cardunculus extract, for 12 weeks. The control group receive a placebo (dummy pill) daily for 12 weeks. Liver fat content is measured at the start and the end of the study.

What are the possible benefits and risks of participating?
All participants receive a liver disease screening for free. No risks are expected.

Where is the study run from?
University Magna Grecia (Italy)

When is the study starting and how long is it expected to run for?
June 2018 to September 2019

Who is funding the study?
Ministry of Education, Universities and Research (Italy)

Who is the main contact?
1. Prof. Arturo Pujia
Pujia@unicz.it
2. Prof. Vincenzo Mollace
Mollace@unicz.it

Contact information

Prof Arturo Pujia
Scientific

viale Europa Campus S. Venuta, Magna Grecia University
sn
Catanzaro
88100
Italy

Phone	+39 (0)3316718206
Email	pujia@unicz.it

Prof Vincenzo Mollace
Scientific

Research Centre for Food Safety and Health (IRC-FSH)
viale Europa
Campus S. Venuta
Magna Grecia University
Catanzaro
88100
Italy

Phone	+39 (0)3316718386
Email	mollace@unicz.it

Study information

Study design	Double-blind placebo-controlled randomized clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Other
Study type	Treatment
Participant information sheet	Not available in web format, please use contact details to request a participant information sheet
Scientific title	Effects of Bergamot (Citrus bergamia Risso et Poiteau) and wild cardoon (Cynara cardunculus L.) extract intake on non-alcoholic fatty liver disease (NAFLD)
Study hypothesis	Given the key roles of oxidation and inflammation in the pathogenesis of liver steatosis and the promising role for natural antioxidants, in this study the aim was to test the effect of a new nutraceutical containing Bergamot and wild Cardoon extract.
Ethics approval(s)	Approved 24/09/2018, local ethical committee at the “Mater Domini” Azienda University Hospital (viale T. Campanella, Catanzaro, Italy; Tel: +39 (0)961 712 111; Email: comitatoetico@hotmail.it; michelangelo.rossano@regione.calabria.it), ref: 219/2018/CE
Condition	Liver steatosis
Intervention	Participants are randomized by simple randomization to: 1. Bergacyn® (provided by Herbal & Antioxidant SRL, Bianco, RC, Italy): one softgel pill containing 300 mg of a combination product containing bergamot polyphenolic fraction (BPF®), and wild type Cynara Cardunculus extract plus excipients including PUFA 380 mg and a mixture of bergamot pulp and albedo derivative]. (registered Patents RM2008A000615, PCT/IB2009/055061 and 102017000040866) 2. Placebo: one softgel pill containing maltodextrin 300 mg plus excipients including PUFA 380 mg Both groups receive the intervention for 12 weeks. Liver fat content, measured by transient elastography (Fibroscan), serum transaminases, lipids and glucose will be measured at the baseline and the end of the study.
Intervention type	Supplement
Primary outcome measure	Liver fat content and/or liver steatosis markers measured by transient elastography (Fibroscan) at baseline and after 12 weeks
Secondary outcome measures	Measured at baseline and after 12 weeks: 1. Disease progression measured by liver elastography 2. Insulin resistance measured by colorimetric test 3. Lipids in blood measured by colorimetric test 4. PCSK9 modulation measured by ELISA/colorimetric test 5. Inflammatory markers measured by colorimetric test 6. Endothelial function and other hemodynamic parameters measured by Endo-PAT
Overall study start date	01/06/2018
Overall study end date	30/09/2019

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	30 Years
Sex	Both
Target number of participants	102
Total final enrolment	102
Participant inclusion criteria	1. Over 30 years old 2. Both genders 3. Liver steatosis defined by CAP score over 216 dB/m
Participant exclusion criteria	1. Past and current alcohol abuse 2. Clinical and laboratory signs of chronic hepatitis B and/or C virus infection 3. Allergies to cardoon, artichoke or maize 4. Triglycerides concentration over 250 mg/dl 5. Autoimmune or cholestatic liver disease 6. Liver cirrhosis 7. Pregnancy 8. Nephrotic syndrome 9. Chronic renal failure 10. Gastroesophageal reflux 11. Cancer 12. Taking amiodarone, antiretroviral agents, corticosteroids, methotrexate, tamoxifen, valproate. The study's protocol allowed to enrol only long-term lipid-lowering drugs users (more than 6 weeks)
Recruitment start date	11/02/2019
Recruitment end date	10/04/2019

Locations

Countries of recruitment

Italy

Study participating centre

Clinical Nutrition Unit of the “Mater Domini” Azienda University Hospital

viale Europa , Campus S. Venuta, University Magna Grecia
Catanzaro
88100
Italy

Sponsor information

Italian Ministry of University and Research (MIUR)
Government

viale G. Ribotta 5
Rome
00144
Italy

Phone	+39 06 59941
Email	minsalute_estero.dgprog@sanita.it
Website	www.salute.gov.it
"ROR"	https://ror.org/0166hxq48

Funders

Funder type

Government

Ministero dell’Istruzione, dell’Università e della Ricerca Nutramed Project, PON 03PE000_78_1
Government organisation / National government

Alternative name(s): Ministry of Education, University and Research, Ministry of Education, Universities and Research, Italian Ministry for Universities and Research, Italian Ministry for Education, University and Research, Italian Ministry of Education, MIUR
Location: Italy

Results and Publications

Intention to publish date	02/06/2019
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Available on request
Publication and dissemination plan	Publication in journal in English with impact factor; mass media.
IPD sharing plan	The datasets generated during and/or analysed during the current study are/will be available upon request from Prof. Pujia (Pujia@unicz.it).

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	11/08/2020	02/09/2020	Yes	No
Results article		26/11/2022	06/09/2023	Yes	No

Editorial Notes

06/09/2023: Publication reference added.
02/09/2020: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been added from the reference.
07/08/2019: Trial's existence confirmed by ethics committee.