Fatty Liver DiseasePhase 1/2PRONENCT04175392
Effect of Probiotics in Non-alcoholic Fatty Liver Disease and Steatohepatitis
A Phase 1/2 study testing Align Probiotic Supplement Capsule in people with Fatty Liver Disease and Fibrosis, Liver, run by Corewell Health East at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Fatty Liver Disease, Fibrosis, Liver, Cirrhosis, Liver
- What is being tested?
- Align Probiotic Supplement Capsule
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Jan 2021to 1 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 19Show fewer
- 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)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Probiotics in Non-Alcoholic Fatty Liver Disease and Steatohepatitis Measured by Transient Elastography (PRONE Study).
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.
Read the 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.
- Being tested
- Align Probiotic Supplement Capsule, Placebos
- Keywords
- Fatty Liver, Fibrosis, Cirrhosis, Probiotic, Steatohepatitis, Elastography
- Medical subject headings
- Non-alcoholic Fatty Liver Disease, Liver Cirrhosis, Fatty Liver, Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Align Probiotic Supplement CapsuleDrug
Also called Probiotic
Align Probiotic 1 billion units, 1 capsule once daily
PlacebosDrug
Also called Placebo
Placebos capsule 1 capsule Once daily
| Study group | Role | What they receive |
|---|---|---|
| Treatment Group: Probiotic | Active comparator | Probiotic 1 billion units Supplement Once Daily Receives: Drug: Align Probiotic Supplement Capsule |
| Control Group: Placebo | Placebo comparator | Placebo Capsule Once Daily Receives: Drug: Placebos |
What is being measured
The primary outcome is the main question the study is designed to answer.
Probiotic Effects on Liver Fibrosis
Probiotic effects on liver fibrosis as measured by transient elastography, as a change from baseline to 6 months, measured on a scale from 1-4. 1= a clinical grade of F0-F1 and represents 2-7 kilopascals in elastography testing. 4= a clinical grade of F4 and represents 14 kilopascals or higher in elastography testing. A higher score on the scale represents worsening liver scarring. Positive numbers indicate an increase in fibrosis; negative numbers indicate decrease in fibrosis.
Measured: 6 months
Secondary outcomes (5)
Probiotic Effects on Liver Enzymes, AST
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
Measured: 6 months
Probiotic Effects on Liver Enzymes, ALT
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
Measured: 6 months
Probiotic Effects on Diabetic Markers
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
Measured: 6 months
Probiotic Effects on BMI
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.
Measured: 6 months
Probiotic Effects on LDL
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
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2019
- Study start12 Jan 2021
- Primary completion1 Mar 2022
- Study completion1 Mar 2022
Why it stopped: lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Fatty Liver DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized, double-blind study. Participant will be randomized to either the Treatment (Probiotic) Group or the Control (Placebo) Group.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Corewell Health East
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariquit Sendelbach, Corewell Health East
- Investigators
- Mariquit Sendelbach, DO, Principal investigator, Corewell Health East
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04175392
- Sponsor's protocol ID
- 2019-129
- Acronym
- PRONE
- Status last verified
- Aug 2022
- First submitted
- 21 Nov 2019
- Last updated
- 27 Sep 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Probiotics in Non-Alcoholic Fatty Liver Disease and Steatohepatitis Measured by Transient Elastography (PRONE Study).
- ClinicalTrials.gov ID
- NCT04175392
- Acronym / sponsor ID
- PRONE / 2019-129
- Keywords
- Fatty Liver, Fibrosis, Cirrhosis, Probiotic, Steatohepatitis, Elastography
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of enrollment
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Corewell Health EastUniversity, hospital or other
- Study start
- 12 Jan 2021 (actual)
- Primary completion
- 1 Mar 2022 (actual)
- Study completion
- 1 Mar 2022 (actual)
- First posted
- 25 Nov 2019 (actual)
- Results
- Posted 27 Sep 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Prospective, randomized, double-blind study. Participant will be randomized to either the Treatment (Probiotic) Group or the Control (Placebo) Group.
| Arm | Type | Receives |
|---|---|---|
| Treatment Group: Probiotic | Active comparator | Drug: Align Probiotic Supplement CapsuleProbiotic 1 billion units Supplement Once Daily |
| Control Group: Placebo | Placebo comparator | Drug: PlacebosPlacebo Capsule Once Daily |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (19 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Align Probiotic Supplement CapsuleAlso: ProbioticAlign Probiotic 1 billion units, 1 capsule once daily | Drug | Treatment Group: Probiotic |
| PlacebosAlso: PlaceboPlacebos capsule 1 capsule Once daily | Drug | Control Group: Placebo |
Primary outcome
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 on a scale from 1-4. 1= a clinical grade of F0-F1 and represents 2-7 kilopascals in elastography testing. 4= a clinical grade of F4 and represents 14 kilopascals or higher in elastography testing. A higher score on the scale represents worsening liver scarring. Positive numbers indicate an increase in fibrosis; negative numbers indicate decrease in fibrosis.
5 secondary outcomes
Probiotic Effects on Liver Enzymes, AST
Time frame: 6 months
Probiotic Effects on Liver Enzymes, ALT
Time frame: 6 months
Probiotic Effects on Diabetic Markers
Time frame: 6 months
Probiotic Effects on BMI
Time frame: 6 months
Probiotic Effects on LDL
Time frame: 6 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mariquit Sendelbach, DO principal investigator
Corewell Health East
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Align Probiotic Supplement Capsule in people with Fatty Liver Disease and Fibrosis, Liver, run by Corewell Health East at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 27 Sep 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Sep 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Probiotic Effects on Liver Fibrosis (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Sep 2022.