Non-Alcoholic Fatty Liver Disease Clinical Trial
— FOIEGRASOfficial title:
Bioenergetic Remodeling in the Pathophysiology and Treatment of Non-Alcoholic Liver Disease
NCT number | NCT03354247 |
Other study ID # | 722619 |
Secondary ID | |
Status | Recruiting |
Phase | N/A |
First received | |
Last updated | |
Start date | July 1, 2017 |
Est. completion date | December 31, 2020 |
Non-Alcoholic Fatty Liver Disease (NAFLD), including its more pathologic consequence,
non-alcoholic steatohepatitis (NASH), is believed to be the most common chronic liver disease
worldwide, affecting between 6 to 37% of the population. NAFLD is a so called 'silent
killer', as clinical symptoms only surface at late stages of the disease, when it is no
longer treatable: untreated, NAFLD/NASH can lead to cirrhosis and hepatocellular carcinoma,
culminating in liver failure. Several factors may contribute to the pathogenesis of NAFLD,
including genetic assessment and mitochondrial dysfunction. Patients with NAFLD/NASH display
disturbances of intestinal permeability, and gut microbiota. In the most of cases, NAFLD/NASH
is strongly linked to other metabolic conditions, including visceral adiposity. Currently the
best method of diagnosing and staging the disease is liver biopsy, a costly, invasive and
somewhat risky procedure, not to mention unfit for routine assessment. Weight loss is the
first step approach with reasonable evidence suggesting it is beneficial and safe in
NAFLD/NASH patients. However, the efficacy of weight reduction for the treatment of
NAFLD/NASH has not been carefully evaluated. Several studies on the effects of weight
reduction on NAFLD/NASH have been uncontrolled, used poorly defined patient populations and
non-standardized weight loss interventions, and lacked a well-accepted primary outcome for
NASH.
The objective of the project is to conduct a randomized controlled trial of 1 year-long
weight reduction in the management of NAFLD/NASH patients using a lifestyle-dietary
intervention program. Overweight or obese individuals with biopsy or ultrasonography (US)
-proven NAFLD/NASH will be randomized to receive either standard medical care and educational
sessions related to NAFLD/NASH, healthy eating, weight loss, and exercise (control group); or
to an intensive weight management with a goal of at least 7-10 % weight reduction (lifestyle
intervention group). The weight loss intervention will be modelled on
Mediterranean-intervention-diet. The investigators hypothesize that a 7-10% weight reduction
through intensive lifestyle intervention will lead to improvement of clinical, US,
anthropometric, and biochemical features on patients diagnosed with NAFLD/NASH.
Status | Recruiting |
Enrollment | 100 |
Est. completion date | December 31, 2020 |
Est. primary completion date | June 30, 2020 |
Accepts healthy volunteers | Accepts Healthy Volunteers |
Gender | All |
Age group | 18 Years to 75 Years |
Eligibility |
Inclusion Criteria: - Patients able to provide informed consent - Certified diagnosis of NAFLD/NASH - Body mass index between 25-40 Kg/m2 - Biohumoral alterations of lipidic and/or glucidic and/or liver metabolism Exclusion Criteria: - Refusal to sign the informed consent - Diagnosis of organic diseases including neoplastic, severe cardiovascular diseases, renal insufficiency, psychiatric disorders - Significant alcohol consumption (> 1 standard drink per day), - Inability to walk 2 blocks or a quarter of a mile without stopping - Engagement in an active weight loss program or taking weight loss medication - Substance abuse - Medication able to affect gastrointestinal tract and to interfere with symptoms - Pregnancy - Presence of diseases with a prognosis of less than 12 months |
Country | Name | City | State |
---|---|---|---|
Italy | Department of Biomedical Sciences Human Oncology - Clinica Medica "A. Murri" | Bari | BA |
Lead Sponsor | Collaborator |
---|---|
University of Bari | European Commission |
Italy,
Bach A, Serra-Majem L, Carrasco JL, Roman B, Ngo J, Bertomeu I, Obrador B. The use of indexes evaluating the adherence to the Mediterranean diet in epidemiological studies: a review. Public Health Nutr. 2006 Feb;9(1A):132-46. Review. — View Citation
Clark JM. Weight loss as a treatment for nonalcoholic fatty liver disease. J Clin Gastroenterol. 2006 Mar;40 Suppl 1:S39-43. Review. — View Citation
Craig CL, Marshall AL, Sjöström M, Bauman AE, Booth ML, Ainsworth BE, Pratt M, Ekelund U, Yngve A, Sallis JF, Oja P. International physical activity questionnaire: 12-country reliability and validity. Med Sci Sports Exerc. 2003 Aug;35(8):1381-95. — View Citation
Diogo CV, Grattagliano I, Oliveira PJ, Bonfrate L, Portincasa P. Re-wiring the circuit: mitochondria as a pharmacological target in liver disease. Curr Med Chem. 2011;18(35):5448-65. Review. — View Citation
Fabbrini E, Sullivan S, Klein S. Obesity and nonalcoholic fatty liver disease: biochemical, metabolic, and clinical implications. Hepatology. 2010 Feb;51(2):679-89. doi: 10.1002/hep.23280. Review. — View Citation
Grattagliano I, de Bari O, Bernardo TC, Oliveira PJ, Wang DQ, Portincasa P. Role of mitochondria in nonalcoholic fatty liver disease--from origin to propagation. Clin Biochem. 2012 Jun;45(9):610-8. doi: 10.1016/j.clinbiochem.2012.03.024. Epub 2012 Mar 28. Review. — View Citation
Hamaguchi M, Kojima T, Itoh Y, Harano Y, Fujii K, Nakajima T, Kato T, Takeda N, Okuda J, Ida K, Kawahito Y, Yoshikawa T, Okanoue T. The severity of ultrasonographic findings in nonalcoholic fatty liver disease reflects the metabolic syndrome and visceral fat accumulation. Am J Gastroenterol. 2007 Dec;102(12):2708-15. Epub 2007 Sep 25. — View Citation
Marventano S, Mistretta A, Platania A, Galvano F, Grosso G. Reliability and relative validity of a food frequency questionnaire for Italian adults living in Sicily, Southern Italy. Int J Food Sci Nutr. 2016 Nov;67(7):857-64. doi: 10.1080/09637486.2016.1198893. Epub 2016 Jun 22. — View Citation
Romero-Gómez M, Zelber-Sagi S, Trenell M. Treatment of NAFLD with diet, physical activity and exercise. J Hepatol. 2017 Oct;67(4):829-846. doi: 10.1016/j.jhep.2017.05.016. Epub 2017 May 23. Review. — View Citation
Rosso C, Mezzabotta L, Gaggini M, Salomone F, Gambino R, Marengo A, Saba F, Vanni E, Younes R, Saponaro C, Buzzigoli E, Caviglia GP, Abate ML, Smedile A, Rizzetto M, Cassader M, Gastaldelli A, Bugianesi E. Peripheral insulin resistance predicts liver damage in nondiabetic subjects with nonalcoholic fatty liver disease. Hepatology. 2016 Jan;63(1):107-16. doi: 10.1002/hep.28287. Epub 2015 Dec 8. Erratum in: Hepatology. 2017 Sep;66(3):1011. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Changes in food intake and Mediterranean diet adherence score | Qualitative nutritional analysis of patients' dietary habits will be measured by a validated 110-items food frequency questionnaire. Change in frequency of intake will be evaluated during the intervention to assess adherence to the Mediterranean diet, according to a validated score. The score goes from 0-18 and classifies the intake of the following 9 items: fruits, vegetables, legumes, cereals, fish, meat and meat products, dairy products, alcohol, and olive oil. Each item is scored from 0-2, depending on the adequacy of the range of habitual intake. For fruits, vegetables, legumes, cereals, fish, and olive oil, the higher the intake the higher the score; for dairy, meat and meat products, the higher the intake, the lower the score; for alcohol, a higher score is given for moderate intake, a 1 score for low intake and a 0 for higher intake. A higher score after intervention is desirable as it represents better adherence to the Mediterranean diet. | 0, 6, 12 months | |
Primary | Changes in physical activity level | Changes in physical activity level will be assessed by a validated physical activity questionnaire. Physical activity level is classified into number of metabolic equivalent of tasks (METs) per minute per week. The range goes from light physical activity level (3 METs/min/week), to moderate (4.5 METs/min/week), to vigorous (6 METs/min/week). Assessment of appropriateness of level of physical activity will be done by comparison with the the recommended by the American College of Sports Medicine / American Heart Association (ACSM/AHA). Changes in level of physical activity will be used to evaluate adherence of the patients to the lifestyle intervention aiming a higher level of physical activity than at baseline (if low) or a maintenance of physical activity level (if already adequate). | 0, 6, 12 months | |
Primary | Changes in body mass index | The body mass index (BMI), composed by weight and height of the patient (kg/m^2) will be used for classification of patients into the following categories according to the World Health Organization: BMI < 18.5 kg/m^2, underweight; BMI 18.5 - 24.9 kg/m^2, normal weight; BMI of 25.0 - 29.9 kg/m^2, overweight; BMI 30.0 - 34.9 kg/m^2, obesity class I; BMI 35.0 - 39.9 kg/m^2, obesity class II; and BMI > 40.0 kg/m^2, obesity class III. Changes in the absolute value and the classification will be evaluated, aiming at a classification of normal weight level or reduction of absolute level. | 0, 6, 12 months | |
Primary | Changes in abdominal girth | The abdominal circumference will be measure and used to classify metabolic risk according to the ATP III criteria -- for men, increased risk when abdominal girth is above 102 cm, and for women, increased risk of circumference over 88 cm. Reductions in the abdominal circumference will be evaluated with the goal of reaching values lower than baseline values, ideally under these cut-off points. | 0, 6, 12 months | |
Primary | Changes in liver steatosis score according to ultrasonography | Evaluation of fat in the liver, as assessed by ultrasonography, can be classified into a score of 0-3, 0 standing for no accumulation of fat in the liver, and 1-3 describing increasing levels of fat accumulation. Changes in this score will be evaluated at selected time points to verify if adherence to the proposed lifestyle changes will reduce the amount of fat accumulation in the liver, and hence, the score. | 0, 6, 12 months |
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