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Effect of Probiotics in Non-alcoholic Fatty Liver Disease and Steatohepatitis (PRONE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04175392
Recruitment Status : Terminated (lack of enrollment)
First Posted : November 25, 2019
Last Update Posted : May 26, 2022
Sponsor:
Information provided by (Responsible Party):
Mariquit Sendelbach, William Beaumont Hospitals

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.

Condition or disease Intervention/treatment Phase
Fatty Liver Disease Fibrosis, Liver Cirrhosis, Liver Steatohepatitis, Nonalcoholic Drug: Align Probiotic Supplement Capsule Drug: Placebos Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 14 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Prospective, randomized, double-blind study. Participant will be randomized to either the Treatment (Probiotic) Group or the Control (Placebo) Group.
Masking: Double (Participant, Investigator)
Masking Description: Both Participants and Researchers will not know which treatment group assigned to.
Primary Purpose: Treatment
Official Title: Effect of Probiotics in Non-Alcoholic Fatty Liver Disease and Steatohepatitis Measured by Transient Elastography (PRONE Study).
Actual Study Start Date : January 12, 2021
Actual Primary Completion Date : March 1, 2022
Actual Study Completion Date : March 1, 2022


Arm Intervention/treatment
Active Comparator: Treatment Group: Probiotic
Probiotic 1 billion units Supplement Once Daily
Drug: Align Probiotic Supplement Capsule
Align Probiotic 1 billion units, 1 capsule once daily
Other Name: Probiotic

Placebo Comparator: Control Group: Placebo
Placebo Capsule Once Daily
Drug: Placebos
Placebos capsule 1 capsule Once daily
Other Name: Placebo




Primary Outcome Measures :
  1. Probiotic effects on liver fibrosis [ Time Frame: 6 months ]
    Probiotic effects on liver fibrosis as measured by transient elastography, as a change from baseline to 6 months, measured in kilopascals (KPa). Positive numbers indicate an increase in fibrosis; negative numbers indicate decrease in fibrosis


Secondary Outcome Measures :
  1. Probiotic effects on Liver enzymes, AST [ Time Frame: 6 months ]
    Probiotic effects on Liver enzymes, AST as a change from baseline to 6 months, measured in units per liter. Positive numbers indicate an increase in AST; negative numbers indicate decrease in AST

  2. Probiotic effects on Liver enzymes, ALT [ Time Frame: 6 months ]
    Probiotic effects on Liver enzymes, ALT as a change from baseline to 6 months, measured in units per liter. Positive numbers indicate an increase in ALT; negative numbers indicate decrease in ALT

  3. Probiotic effects on Diabetic Markers [ Time Frame: 6 months ]
    Probiotic effects on Diabetic Markers as measured by hemoglobin A1C blood test as a change from baseline to 6 months, measured in percent. Positive numbers indicate an increase in hemoglobin A1c; negative numbers indicate decrease in hemoglobin A1c

  4. Probiotic effects on BMI [ Time Frame: 6 months ]
    Probiotic effects on Body Mass Index (BMI) wherein weight and height will be combined to report BMI in kg/m^2 as a change from baseline to 6 months. Positive numbers indicate an increase in BMI; negative numbers indicate decrease in BMI.

  5. Probiotic effects on LDL [ Time Frame: 6 months ]
    Probiotic effects on Low-density Lipoprotein (LDL) as a change from baseline to 6 months, measured in milligrams per deciliter. Positive numbers indicate an increase in LDL; negative numbers indicate decrease in LDL



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04175392


Locations
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United States, Michigan
Beaumont Hospital
Farmington Hills, Michigan, United States, 48336
Sponsors and Collaborators
William Beaumont Hospitals
Investigators
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Principal Investigator: Mariquit Sendelbach, DO William Beaumont Hospitals
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Responsible Party: Mariquit Sendelbach, Principal Investigator, William Beaumont Hospitals
ClinicalTrials.gov Identifier: NCT04175392    
Other Study ID Numbers: 2019-129
First Posted: November 25, 2019    Key Record Dates
Last Update Posted: May 26, 2022
Last Verified: May 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Keywords provided by Mariquit Sendelbach, William Beaumont Hospitals:
Fatty Liver
Fibrosis
Cirrhosis
Probiotic
Steatohepatitis
Elastography
Additional relevant MeSH terms:
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Liver Cirrhosis
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Fibrosis
Pathologic Processes
Digestive System Diseases