Fighting Fatty Liver in India (FFL)

Fighting the Fatty Liver Pandemic: Developing Effective Protocols & Local Expertise to Deliver & Evaluate Diet/Lifestyle Interventions for Better Liver & Metabolic Health in India

This study aims to build capacity in India by:

1. Developing tailored protocol methodologies for research including technical capability in imaging (MRI/S protocols & customised software), dietary intervention delivery, dietary evaluation, and biochemical analyses, using available local resources in Kerala.
2. Training and enhancing imaging skills of clinical radiographers in Kerala for research studies
3. Training local professionals and researchers in skills necessary to design, deploy and evaluate diet/lifestyle interventions, including patient engagement, in Kerala.

This study will deliver and evaluate a simple dietary intervention pilot study in the Kerala region in conjunction with local nutritionists, healthcare professionals and partner researchers at PHRI (Population Health and Research Institute, Trivandrum, Kerala, India).

Study Overview

• Status: Unknown
• Conditions: NAFLD
• Intervention / Treatment: Behavioral: Diet change (red rice); Behavioral: Yoga

Detailed Description

STUDY BACKGROUND INFORMATION AND RATIONALE

Non-alcoholic fatty liver disease (NAFLD):

With an estimated global prevalence of 25% among adults, NAFLD is now the commonest chronic liver disease; its progressive form, non-alcoholic steatohepatitis (NASH), has been estimated to affect 1.5%-6.5% of the population with associated increased risk of cirrhosis, hepatocellular carcinoma and liver-specific mortality. Considering the key association of fat accumulation within the liver, in particular diacyl glycerols, to the generation of whole body insulin resistance and development of type 2 diabetes, NAFLD has been considered a pre-diabetic state. NAFLD has been associated with excess risk of non-fatal and fatal cardiovascular events independently of established co-morbidities including type 2 diabetes, dyslipidemia and obesity. Individuals of South Asian ethnicity have significantly higher rates of NAFLD, abdominal obesity and cardiovascular disease than whites and ethnicity is a risk factor for NAFLD independent of diabetes, BMI, hypertension and hypercholesterolemia.

NAFLD problem in India:

Consistent with the global trend, the health and economic burdens of metabolic syndrome and NAFLD have risen in India. In 2011, India had 63 million individuals with type 2 diabetes and by 2030, that number is predicted to be a staggering 90 million. Insulin resistance (IR) has also been shown to be more prevalent in Indians compared with other ethnic groups and this has been correlated with NAFLD regardless of adiposity. Despite these links, there are a number of key differences between Indian NAFLD patients and those in the West: mean BMI is significantly lower in Indians and there is also a lower prevalence of hypertension, diabetes and metabolic syndrome in non-cirrhotic NAFLD patients.

Dietary influences on NAFLD:

Diet may be one of the key environmental factors that accounts for ethnic variation in susceptibility to NAFLD. However, there is currently a lack of research into specific dietary factors influencing susceptibility to NAFLD, in particular, with regards to macronutrients, and there are few evidence-based dietary interventions, beyond energy restriction to induce weight loss. Considering the effectiveness of a modest increase in protein content and a reduction in the glycaemic index (GI) in maintaining weight loss, we investigated the effects of a low GI diet on the liver and demonstrated that it did not increase liver fat content whereas an increase was seen with an isoenergetic high GI diet controlled for macronutrient content.

Diet has been found to influence the gut microbiome variably across human societies. Fibre encompassing a range of characteristics, is one of the fundamental components linking diet, the gut microbiome and fatty acid metabolism. The benefits of dietary fibre include improved glucose homeostasis and insulin sensitivity. Dietary fibres are at least partly fermented in the caecum and large intestine by the colonic microbiota resulting in some cases an increased production of short chain fatty acids (SCFAs) which regulate the balance between fatty acid synthesis, fatty acid oxidation and lipolysis in the body. The net result is a reduction in free fatty acid concentrations in plasma and a decrease in body weight. Dietary fibre overall is associated with greater gut microbiome diversity and we have recently shown that it is also associated with lower long-term weight gain.

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Kerala
    • Trivandrum, Kerala, India
      • Recruiting
      • Population Health and Research Institute
      • Contact: Thrivikrama Shenoy; Email: dr.ktshenoy@gmail.com
      • Contact: Leena Mohan; Email: leenakb@yahoo.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion criteria

• aged 18 years or over
• Male
• Able to give informed consent
• NAFLD diagnosis showing Fatty/echo-bright liver on ultrasound within past 3 months
• Able to attend yoga sessions
• Able to undergo MRI
• Consumer of at least 300g (uncooked weight) white rice per day (on average)
• No allergy to red rice or lentils
• Medically suitable for repeated blood sampling

Exclusion criteria

• Known or suspected cirrhosis on clinical/histological/radiological grounds
• Current or recent history of significant alcohol consumption (>14units per week)

• Other documented causes of chronic liver disease including:

  • Hepatitis B or C infection
  • Drug-induced liver disease
  • Alcohol-related liver disease
  • Autoimmune hepatitis
  • Wilson's disease, Haemachromatosis
  • Primary biliary cirrhosis, Primary Sclerosing Cholangitis
• Currently taking medication that can induce steatosis (corticosteroids, Amiodarone, Tamoxifen, Methotrexate)
• Evidence of any other unstable or untreated clinically significant immunological, endocrine, haematological, gastrointestinal, neurological, neoplastic or psychiatric disease

• *Female

  • A number of gender specific confounders (menstrual cycle, age etc) mean that mechanistic studies in small sample sizes are limited to men. The local cohort being used comprises males only.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Diet change (red rice) with yoga; Following randomisation, participants are given a schedule of group and personal meetings and details of each session. Food for the diet (red rice and lentils) will be provided for those randomised to the diet arm. The study will last 16 weeks following start of the diet/yoga programme. There will be further visits to measure outcomes at week 8 and week 16. All participants in both arms will complete the same programme of Yoga sessions, organized and delivered by experienced practitioners under direction of Dr Leena Mohan at the Holistic Health and Research Institute.	Behavioral: Diet change (red rice); This interventions specifically aims to reduce liver inflammation, by replacing white rice in the diet with equal amounts of red rice and lentils. This will also enable for the research team to tests specific scientific hypotheses regarding the effects of diet on insulin resistance, liver pathology and the gut microbiome in NAFLD.; Behavioral: Yoga; All 84 study participants take part in the yoga intervention. This is an intensive programme organized and delivered by experienced practitioners under direction of Dr Leena Mohan at the Holistic Health and Research Institute. This will evaluate whether physical activity alone improves metabolic health of the liver.
ACTIVE_COMPARATOR: Yoga; Following randomisation, participants are given a schedule of group and personal meetings and details of each session. The study will last 16 weeks following start of the diet/yoga programme. There will be further visits to measure outcomes at week 8 and week 16. All participants in both arms will complete the same programme of Yoga sessions, organized and delivered by experienced practitioners under direction of Dr Leena Mohan at the Holistic Health and Research Institute.	Behavioral: Yoga; All 84 study participants take part in the yoga intervention. This is an intensive programme organized and delivered by experienced practitioners under direction of Dr Leena Mohan at the Holistic Health and Research Institute. This will evaluate whether physical activity alone improves metabolic health of the liver.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in liver fat	Measured by MRI, comparing liver fat pre- and post-intervention.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in body composition	Measured by body fat % via bioimpedance	1 year
Change in body composition	Measured by BMI (kg/m2)	1 year
Change in insulin sensitivity	Measured by oral glucose tolerance test (OGTT)	1 year

Collaborators and Investigators

• Sponsor: University of Nottingham
• Collaborators: Population Health and Research Institute, Trivandrum, Kerala, india; Holistic Health and Research Institute, Trivandrum, Kerala, India

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 1, 2019
• Primary Completion (ANTICIPATED): July 31, 2019
• Study Completion (ANTICIPATED): December 31, 2019

Study Registration Dates

• First Submitted: February 11, 2019
• First Submitted That Met QC Criteria: February 13, 2019
• First Posted (ACTUAL): February 18, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 18, 2019
• Last Update Submitted That Met QC Criteria: February 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Liver Diseases; Fatty Liver
• Other Study ID Numbers: 137 1811

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No