Clinical trial NCT03132662: Omega-3 vs Very Low Calorie Diet for Liver Size Reduction
Official title: Comparative Trial of Omega-3 Polyunsaturated Fatty Acids vs a Very Low Calorie Liquid Diet for Liver Volume Reduction Prior to Bariatric Surgery
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Obesity, Morbid
Obesity
NAFLD
NASH - Nonalcoholic Steatohepatitis
Lead sponsor: McMaster University
Sponsor class: OTHER
Collaborators: name: Neptune
First posted: 2017-04-28
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: A recent review demonstrated that Non-alcoholic fatty liver disease (NAFLD) affects 10-35% of the adult population worldwide, with the prevalence approaching 85-100% in obese populations. Current standard treatment for liver reduction before surgery is the use of a very low calorie liquid diet (VLCLD). Multiple studies have shown that a 2-4 week diet with a VLCD will reduce liver volume, in preparation for surgery. Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for NAFLD. The primary aim of this study is to compare Ω-3 PUFAs and a VLCLD and their effect on left lobe live size before bariatric surgery.

Detailed description: Non-alcoholic fatty liver disease (NAFLD) is defined by the pathological accumulation of fat in the liver when no other explanatory disease is present: it encompasses isolated hepatic steatosis, non-alcoholic steatohepatitis (NASH) cirrhosis, and is a frequent accompaniment of obesity and insulin resistance. A recent review demonstrated that NAFLD affects 10-35% of the adult population worldwide, with the prevalence approaching 85-100% in obese populations.

Although frequently asymptomatic and relatively benign, NAFLD has the potential to progress to cirrhosis. Cirrhosis, when decompensated, has a poor prognosis.

Also, NAFDL will be accompanied invariably with increased liver volume, which will directly increase the level of difficulty of upper gastrointestinal surgery, such as bariatric surgery, specifically for the visualization of the gastro-esophageal junction. Bleeding is also more frequent with larger fattier left liver lobes. The combination of these factors may lead to conversion to open surgery, thus: increasing postoperative pain due to larger incisions, prolonging postoperative recovery times and increasing the risks of infection and hernias.

Current standard treatment for liver reduction before surgery is the use of a very low calorie liquid diet (VLCLD). Multiple studies have shown that a 2-4 week diet with Optifast® will reduce liver volume, in preparation for surgery.

Omega-3 (Ω-3) polyunsaturated fatty acids (PUFAs) have been suggested as a treatment for NAFLD. They have several potential mechanisms of action, the most important being to alter hepatic gene expression, thereby switching intracellular metabolism from lipogenesis and storage to fatty acid oxidation and catabolism. There is also evidence that they improve insulin sensitivity, are anti-inflammatory and reduce TNF levels lipogenesis thus offering several potential therapeutic mechanisms.

Eligibility criteria: Inclusion Criteria:

Participants must meet ALL of the following inclusion criteria:

* Fulfilled criteria for bariatric surgery as coined by National Institutes of Health conference (a body mass index (BMI) of 40 or more, OR a BMI of 35 or more with a serious health problem linked to obesity, such as type 2 diabetes, heart disease, or sleep apnea)
* Their age is ≥18 years and ≤70 years
* Able and willing to give written consent
* The patient is willing to perform the pre-operative tests required for this study.

Exclusion Criteria:

Participants who meet any of the following criteria at the time of the baseline visit are NOT eligible to be enrolled in this study:

* Prior bariatric surgery
* Patient must not have any acute or chronic alteration of liver function (i.e. cirrhosis, active or chronic hepatitis, congenital hepatic disease, etc.)
* Prior hepatic surgery
* Contra-indication to general anesthesia
* Any medical condition, which in the judgement of the Investigator and/or designee makes the subject a poor candidate for the investigational procedure
* Pregnant or lactating female (Women of child bearing potential must take a pregnancy test prior to surgery)
* Patients receiving medication that would alter hepatic function significantly.
* Patients with ascites.
* History of alcohol abuse: \>3 standard drinks/day in men or \>2 standard drinks/day in women (one standard drink being defined as 12 ounces of 5% beer, 5 ounces of 12% wine or 1.5 ounces of 40% liquor).
* Patients consuming Ω-3 supplements on a regular basis.

Primary outcomes:
measure: Left liver lobe size
timeFrame: First ultrasound will be done before treatment. Second ultrasound will be done after the treatment period of 3 weeks, before bariatric surgery is completed
Secondary outcomes:
measure: NAFLD
timeFrame: First ultrasound will be done before treatment. Second ultrasound will be done after the treatment period of 3 weeks, before bariatric surgery is completed
measure: Costs
timeFrame: After the treatment period of 3 weeks, before bariatric surgery is completed
Other outcomes:
Locations:
Study officials:
affiliation: McMaster University
name: Dennis Hong, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bellentani S, Marino M. Epidemiology and natural history of non-alcoholic fatty liver disease (NAFLD). Ann Hepatol. 2009;8 Suppl 1:S4-8.
citation: Hui JM, Kench JG, Chitturi S, Sud A, Farrell GC, Byth K, Hall P, Khan M, George J. Long-term outcomes of cirrhosis in nonalcoholic steatohepatitis compared with hepatitis C. Hepatology. 2003 Aug;38(2):420-7. doi: 10.1053/jhep.2003.50320.
citation: Masterton GS, Plevris JN, Hayes PC. Review article: omega-3 fatty acids - a promising novel therapy for non-alcoholic fatty liver disease. Aliment Pharmacol Ther. 2010 Apr;31(7):679-92. doi: 10.1111/j.1365-2036.2010.04230.x.
citation: Parker HM, Johnson NA, Burdon CA, Cohn JS, O'Connor HT, George J. Omega-3 supplementation and non-alcoholic fatty liver disease: a systematic review and meta-analysis. J Hepatol. 2012 Apr;56(4):944-51. doi: 10.1016/j.jhep.2011.08.018. Epub 2011 Oct 21.
citation: Clarke SD. Nonalcoholic steatosis and steatohepatitis. I. Molecular mechanism for polyunsaturated fatty acid regulation of gene transcription. Am J Physiol Gastrointest Liver Physiol. 2001 Oct;281(4):G865-9. doi: 10.1152/ajpgi.2001.281.4.G865.
citation: Svegliati-Baroni G, Candelaresi C, Saccomanno S, Ferretti G, Bachetti T, Marzioni M, De Minicis S, Nobili L, Salzano R, Omenetti A, Pacetti D, Sigmund S, Benedetti A, Casini A. A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol. 2006 Sep;169(3):846-60. doi: 10.2353/ajpath.2006.050953.
citation: Bellentani S, Saccoccio G, Masutti F, Croce LS, Brandi G, Sasso F, Cristanini G, Tiribelli C. Prevalence of and risk factors for hepatic steatosis in Northern Italy. Ann Intern Med. 2000 Jan 18;132(2):112-7. doi: 10.7326/0003-4819-132-2-200001180-00004.
citation: Lewis MC, Phillips ML, Slavotinek JP, Kow L, Thompson CH, Toouli J. Change in liver size and fat content after treatment with Optifast very low calorie diet. Obes Surg. 2006 Jun;16(6):697-701. doi: 10.1381/096089206777346682.
citation: Colles SL, Dixon JB, Marks P, Strauss BJ, O'Brien PE. Preoperative weight loss with a very-low-energy diet: quantitation of changes in liver and abdominal fat by serial imaging. Am J Clin Nutr. 2006 Aug;84(2):304-11. doi: 10.1093/ajcn/84.1.304.
citation: Cohen JC, Horton JD, Hobbs HH. Human fatty liver disease: old questions and new insights. Science. 2011 Jun 24;332(6037):1519-23. doi: 10.1126/science.1204265.
citation: Capanni M, Calella F, Biagini MR, Genise S, Raimondi L, Bedogni G, Svegliati-Baroni G, Sofi F, Milani S, Abbate R, Surrenti C, Casini A. Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study. Aliment Pharmacol Ther. 2006 Apr 15;23(8):1143-51. doi: 10.1111/j.1365-2036.2006.02885.x.
citation: Spadaro L, Magliocco O, Spampinato D, Piro S, Oliveri C, Alagona C, Papa G, Rabuazzo AM, Purrello F. Effects of n-3 polyunsaturated fatty acids in subjects with nonalcoholic fatty liver disease. Dig Liver Dis. 2008 Mar;40(3):194-9. doi: 10.1016/j.dld.2007.10.003. Epub 2007 Dec 4.
citation: Iannelli A, Martini F, Schneck AS, Ghavami B, Baudin G, Anty R, Gugenheim J. Preoperative 4-week supplementation with omega-3 polyunsaturated fatty acids reduces liver volume and facilitates bariatric surgery in morbidly obese patients. Obes Surg. 2013 Nov;23(11):1761-5. doi: 10.1007/s11695-013-0942-y.