Back to resultsAnti-LPS Antibody Treatment for Pediatric NAFLD
Primary Purpose
Nonalcoholic Fatty Liver Disease (NAFLD)
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
IMM-124E
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Nonalcoholic Fatty Liver Disease (NAFLD)
Eligibility Criteria
Inclusion Criteria:
- Nonalcoholic fatty liver disease (NAFLD) diagnosis confirmed by liver biopsy or MRI
- ALT ≥ 2 x ULN at screening (girls ≥ 46, boys ≥ 54)
- Written informed parent consent and child assent
- Willingness to take IMM-124E or placebo powder 3 x daily for 12 weeks
- At least 2 months of attempted lifestyle changes after diagnosis
Exclusion Criteria:
- Disease or condition deemed by physician to interfere with absorption, digestion, or mechanism of intervention of drug
- Diagnosis of diabetes and an HbA1c of > 9%
- Change in supplement or anti-oxidant therapy within past 90 days (must be on a stable dose and willing to continue it throughout the trial or not on any vitamin or supplement, includes SAMe, vitamin E, betaine, Milk thistle etc)
- Use of probiotics or antibiotics in the past 30 days
- Use of anti-NAFLD medications (metformin, thiazolidinediones, UDCA) in the 30 days prior to randomization
- Acute illness within past 2 weeks prior to enrollment (defined as fever > 100.4ºF)
- Planned pregnancy, nursing an infant, confirmed or suspected to be pregnant between screening and time of study enrollment
- Evidence of other chronic liver disease other than NAFLD (Hepatitis B and C, Alpha-1 antitrypsin, Wilson's disease)
- Intolerance to lactose or dairy-based products
- Unable to have blood drawn at study visits
- Unwillingness to provide and/or collect stool samples
- Current gastrointestinal (GI) bleeding or inflammatory bowel disease (irritable bowel disease (IBD), colitis)
- Current enrollment in another therapeutic clinical trial or receipt of an investigational study drug within 6 months prior to study enrollment
- Participants who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator
Sites / Locations
- Children's Healthcare of Atlanta
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
IMM-124E Group
Placebo Group
Arm Description
Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.
Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.
Outcomes
Primary Outcome Measures
Percent Change in Alanine Aminotransferase (ALT) Level
Percent change in ALT level from baseline to end of treatment.
Secondary Outcome Measures
Percent Change in Fasting Glucose Level
Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.
Change in Fasting Insulin Level
Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.
Change in Hemoglobin A1C Level
Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.
Change in Adipose Tissue Insulin Resistance (Adipo-IR)
Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.
Change in Triglyceride/HDL (TG/HDL) Ratio
The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.
Percent Change in Blood Glucose Level
The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.
Change in Insulin Levels
The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.
Percent Change in Body Mass Index (BMI) Z-Score
BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.
Percent Change in Visceral Adiposity
Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.
Percent Change in Hepatic Fat Percent
Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.
Percent Change in Waist Circumference
Waist circumference will be measured in centimeters using measuring tape.
Percent Change in PROMIS Fatigue Questionnaire Score
The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.
Percent Change in PROMIS Depression Questionnaire Score
The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.
Percent Change in PROMIS Anxiety Questionnaire Score
The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.
Composite Metabolic Improvement
Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.
Full Information
NCT ID
NCT03042767
First Posted
February 2, 2017
Last Updated
April 26, 2021
Sponsor
Miriam Vos, MD
Collaborators
Advanced MR Analytics AB, Immuron Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT03042767
Brief Title
Anti-LPS Antibody Treatment for Pediatric NAFLD
Official Title
Anti-LPS Antibody in Pediatric Nonalcoholic Fatty Liver Disease
Study Type
Interventional
2. Study Status
Record Verification Date
April 2021
Overall Recruitment Status
Completed
Study Start Date
February 1, 2017 (Actual)
Primary Completion Date
October 23, 2019 (Actual)
Study Completion Date
October 23, 2019 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Miriam Vos, MD
Collaborators
Advanced MR Analytics AB, Immuron Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The main objective of this pilot study is to evaluate whether 12 weeks of IMM-124E in children with nonalcoholic fatty liver disease (NAFLD) in combination with standard of care treatment will decrease inflammation in the liver as measured by alanine transaminase (ALT). Specifically, investigators will measure percent change in ALT from Week 0 to Week 12 in treatment compared to placebo.
Detailed Description
This is a randomized, double blind, placebo controlled, three month treatment trial of children aged 6-19 years. Participants will be recruited from the Children's Healthcare of Atlanta pediatric liver clinical practice.The purpose of this study is to evaluate if a three month treatment with IMM-124E (a bovine colostrum enriched with anti-LPS antibodies) in combination with standard of care lifestyle advice is safe and leads to greater improvement in hepatic inflammation, insulin sensitivity, and blood lipids in children with nonalcoholic fatty liver disease (NAFLD) compared to placebo with standard of care treatment. Investigators also seek to define the mechanism of action in response to three months of treatment with IMM-124E.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Nonalcoholic Fatty Liver Disease (NAFLD)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
IMM-124E Group
Arm Type
Experimental
Arm Description
Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.
Arm Title
Placebo Group
Arm Type
Placebo Comparator
Arm Description
Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.
Intervention Type
Biological
Intervention Name(s)
IMM-124E
Intervention Description
IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
Matched Placebo
Primary Outcome Measure Information:
Title
Percent Change in Alanine Aminotransferase (ALT) Level
Description
Percent change in ALT level from baseline to end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Secondary Outcome Measure Information:
Title
Percent Change in Fasting Glucose Level
Description
Fasting glucose level will be collected via blood draw. Percent Change in glucose levels between baseline and end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Change in Fasting Insulin Level
Description
Fasting insulin level will be collected via blood draw. Change is the difference in insulin level from baseline to end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Change in Hemoglobin A1C Level
Description
Hemoglobin A1C Level will be collected via blood draw. Change is the difference in hemoglobin AIC level from baseline to end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Change in Adipose Tissue Insulin Resistance (Adipo-IR)
Description
Adipo-IR will be collected via blood draw. It is calculated as fasting non-esterified fatty acids x fasting insulin.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Change in Triglyceride/HDL (TG/HDL) Ratio
Description
The TG/HDL ratio is the proportion of triglyceride levels in relation to HDL (good cholesterol). Change is defined as the difference in the TG/HDL ratio from baseline to the end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in Blood Glucose Level
Description
The blood glucose level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the glucose level will be tested by a blood draw every thirty minutes for two hours. Percentage change between glucose measurements taken at baseline and at the end of treatment is reported.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Change in Insulin Levels
Description
The insulin level will be monitored via an oral glucose tolerance test (OGTT) at baseline and at the end of treatment. During the OGTT, the insulin level will be tested by a blood draw every thirty minutes for two hours. Change is described as the difference between insulin measurements taken at baseline and at the end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in Body Mass Index (BMI) Z-Score
Description
BMI will be calculated from height and weight and converted into a z-score. Body mass index z-scores are measures of relative weight adjusted for age and sex.Change is the difference in BMI z-scores from base line to end of treatment.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in Visceral Adiposity
Description
Visceral adiposity will be measured with a magnetic resonance imaging (MRI) scan. Visceral adipose tissue is a hormonally active component of total body fat.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in Hepatic Fat Percent
Description
Hepatic fat percent will be measured with a magnetic resonance imaging (MRI) scan. Hepatic fat percent is the percentage of fat within the liver.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in Waist Circumference
Description
Waist circumference will be measured in centimeters using measuring tape.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in PROMIS Fatigue Questionnaire Score
Description
The PROMIS Fatigue questionnaire evaluates a range of self-reported symptoms, from mild subjective feelings of tiredness to an overwhelming, debilitating, and sustained sense of exhaustion that likely decreases one's ability to execute daily activities and function normally in family or social roles. Fatigue is divided into the experience of fatigue (frequency, duration, and intensity) and the impact of fatigue on physical, mental, and social activities. It assesses fatigue over the past seven days. A higher score represents more symptoms of fatigue.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in PROMIS Depression Questionnaire Score
Description
The PROMIS Depression instruments assess self-reported negative mood (sadness, guilt), views of self (selfcriticism, worthlessness), and social cognition (loneliness, interpersonal alienation), as well as decreased positive affect and engagement (loss of interest, meaning, and purpose). It assesses depression over the past seven days. A higher score represents more symptoms of depression.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Percent Change in PROMIS Anxiety Questionnaire Score
Description
The PROMIS Anxiety instruments measure self-reported fear (fearfulness, panic), anxious misery (worry, dread), hyperarousal (tension, nervousness, restlessness), and somatic symptoms related to arousal (racing heart, dizziness). Anxiety is best differentiated by symptoms that reflect autonomic arousal and experience of threat. Each assesses anxiety over the past seven days. A higher score represents more symptoms of anxiety.
Time Frame
Baseline (Week 0), End of Treatment (Week 12)
Title
Composite Metabolic Improvement
Description
Composite metabolic improvement is defined as greater than 10% improvement in TG/HDL ratio, improvement in insulin resistance, and greater than 10% improvement in ALT.
Time Frame
End of Treatment (Week 12)
10. Eligibility
Sex
All
Minimum Age & Unit of Time
6 Years
Maximum Age & Unit of Time
19 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Nonalcoholic fatty liver disease (NAFLD) diagnosis confirmed by liver biopsy or MRI
ALT ≥ 2 x ULN at screening (girls ≥ 46, boys ≥ 54)
Written informed parent consent and child assent
Willingness to take IMM-124E or placebo powder 3 x daily for 12 weeks
At least 2 months of attempted lifestyle changes after diagnosis
Exclusion Criteria:
Disease or condition deemed by physician to interfere with absorption, digestion, or mechanism of intervention of drug
Diagnosis of diabetes and an HbA1c of > 9%
Change in supplement or anti-oxidant therapy within past 90 days (must be on a stable dose and willing to continue it throughout the trial or not on any vitamin or supplement, includes SAMe, vitamin E, betaine, Milk thistle etc)
Use of probiotics or antibiotics in the past 30 days
Use of anti-NAFLD medications (metformin, thiazolidinediones, UDCA) in the 30 days prior to randomization
Acute illness within past 2 weeks prior to enrollment (defined as fever > 100.4ºF)
Planned pregnancy, nursing an infant, confirmed or suspected to be pregnant between screening and time of study enrollment
Evidence of other chronic liver disease other than NAFLD (Hepatitis B and C, Alpha-1 antitrypsin, Wilson's disease)
Intolerance to lactose or dairy-based products
Unable to have blood drawn at study visits
Unwillingness to provide and/or collect stool samples
Current gastrointestinal (GI) bleeding or inflammatory bowel disease (irritable bowel disease (IBD), colitis)
Current enrollment in another therapeutic clinical trial or receipt of an investigational study drug within 6 months prior to study enrollment
Participants who are not able or willing to comply with the protocol or have any other condition that would impede compliance or hinder completion of the study, in the opinion of the investigator
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Miriam Vos, MD, MSPH
Organizational Affiliation
Emory University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Children's Healthcare of Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Anti-LPS Antibody Treatment for Pediatric NAFLD
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