Clinical trial NCT04175392: Effect of Probiotics in Non-alcoholic Fatty Liver Disease and Steatohepatitis
Official title: Effect of Probiotics in Non-Alcoholic Fatty Liver Disease and Steatohepatitis Measured by Transient Elastography (PRONE Study).
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Fatty Liver Disease
Fibrosis, Liver
Cirrhosis, Liver
Steatohepatitis, Nonalcoholic
Keywords: Fatty Liver
Fibrosis
Cirrhosis
Probiotic
Steatohepatitis
Elastography
Lead sponsor: William Beaumont Hospitals
Sponsor class: OTHER
First posted: 2019-11-25
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Prospective, randomized, double-blind study. Participant will be randomized to either the Treatment (Probiotic) Group or the Control (Placebo) Group.
Primary purpose: TREATMENT

Brief summary: This study will evaluate the effect of probiotics, a beneficial intestinal bacteria supplement, if it will cause improvement of the non-alcoholic fatty liver disease (NAFLD) and or non-alcoholic steatohepatitis (NASH- an inflammation with concurrent fatty accumulation of the liver) as measured by transient elastography - an ultrasound of the liver that assess the elastic properties (density) and stiffness of the liver tissue. This study will enroll patients 18 years and older with diagnosis of NAFLD and or NASH.

Detailed description: Non-Alcoholic Fatty Liver Disease (NAFLD) and Non-Alcoholic Steatohepatitis (NASH) are conditions without symptoms where inflammation in the liver can progress to end-stage liver disease (cirrhosis). Current standard of care for these conditions include control of metabolic syndrome which includes but is not limited to a patient's high blood pressure (hypertension), high cholesterol (hyperlipidemia), high blood sugar (hyperglycemia) and excess fat around the waist (central obesity and waist circumference) with lifestyle modifications including diet, exercise and medications. While the mechanism for inflammation on the liver in NAFLD and NASH is not completely understood, the American Association for the Study of Liver Diseases currently suspects it may be connected with the metabolism in the bowel and subsequent hepatic (liver) circulation. The bacteria of the intestines (microbiome or gut flora) may play a role in the inflammatory cascade through the bloodstream that affects the liver.

The World Health Organization (WHO) and the Food and Agricultural Organization (FAO) of the United Nations define Probiotics as a "live microorganism" which, when taken in adequate amounts confer a health benefit in the gastrointestinal tract. This study will be done to determine if probiotic use may be a viable treatment option for NAFLD and NASH and to establish a link that the intestinal microbiome or gut flora plays a role in liver inflammation which will be measured by elastography.

Patients with NAFLD and NASH seen in office consultation of the investigator will be approached to participate in the randomized like a flip of a coin, double-blind (patients and researchers will be blinded), placebo controlled study. Participant will be counseled on diet and exercise. The participants will receive information on a standardized Mediterranean diet based nutrition program as well as direction for recommended 30 minutes of aerobic exercise 3 times weekly. A baseline transient elastography, blood test such as liver enzymes Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) will be drawn, including hemoglobin A1C (diabetic marker), cholesterol in the form of Low-Density Lipoprotein (LDL/bad cholesterol) and assessment of Body Mass Index (BMI).

Participants will be randomized by pharmacy into 2 groups, a control group and a treatment group. The treatment group will be provided with a 6 month supply of Align probiotic once daily supplementation; the control group will be given a placebo for 6 months along with both groups given instructions on how to take the supplement. Subjects will receive a 1 month phone call follow up to ensure adherence to study instructions and daily oral intake of supplement, and again at 3 months. Study participation will end at 6 months after the repeat of liver enzymes, hemoglobin A1C, lipid panel, assessment of BMI and transient elastography as completed at scheduled clinical appointment.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of NAFLD and/or NASH
* Subject aged 18 and older
* Non-pregnant - Self-reported
* Subject with decision making capacity to understand and consent to study procedures
* Ability to follow study related activities regarding medications, diet and exercise

Exclusion Criteria:

* Without diagnosis of NAFLD or NASH
* History of liver disease from other causes, including but not limited to hepatitis, autoimmune, alcohol use, fatty liver of pregnancy, Wilson's disease, primary or secondary hemochromatosis
* Patients aged less than 18 years
* Self-reported pregnant patients
* Inability to understand, follow and consent to study procedures
* Hepatic decompensation defined as gastrointestinal bleeding, ascites, hepatic encephalopathy
* Inability to engage in exercise
* Currently immunocompromised or taking immunosuppressive drugs
* Milk protein allergy
* Recent or active chemotherapy for malignancy
* Gastrointestinal malignancy
* Gastrointestinal disease such as Ulcerative Colitis, Crohn's Disease as these alter the microbiome
* Recent antibiotic therapy (within 6 months)
* Known allergy to probiotics
* History of major gastrointestinal surgery such as resection of the colon
* No concomitant use of probiotic from any source (i.e., kefir, certain yogurts, live culture, sauerkraut)
* Liver scan \>2 months prior to enrollment
* Weight loss \>5 pounds in the last 2 months
* Any implanted battery operated device (i.e. AICD, pacemaker, loop recorder, cochlear implant)

Primary outcomes:
measure: Probiotic Effects on Liver Fibrosis
timeFrame: 6 months
Secondary outcomes:
measure: Probiotic Effects on Liver Enzymes, AST
timeFrame: 6 months
measure: Probiotic Effects on Liver Enzymes, ALT
timeFrame: 6 months
measure: Probiotic Effects on Diabetic Markers
timeFrame: 6 months
measure: Probiotic Effects on BMI
timeFrame: 6 months
measure: Probiotic Effects on LDL
timeFrame: 6 months
Other outcomes:
Locations:
city: Farmington Hills
country: United States
facility: Beaumont Hospital
state: Michigan
Study officials:
affiliation: William Beaumont Hospitals
name: Mariquit Sendelbach, DO
role: PRINCIPAL_INVESTIGATOR
References: