Nonalcoholic Fatty Liver Disease (NAFLD)
Conditions
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.
Interventions
BIOLOGICALIMM-124E
IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring.
OTHERPlacebo
Matched Placebo
Sponsors
Miriam Vos, MD
Advanced MR Analytics AB
Immuron Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
6 Years to 19 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Alanine Aminotransferase (ALT) Level | Baseline (Week 0), End of Treatment (Week 12) | Percent change in ALT level from baseline to end of treatment. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Fasting Glucose Level | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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) | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 Waist Circumference | Baseline (Week 0), End of Treatment (Week 12) | Waist circumference will be measured in centimeters using measuring tape. |
| Percent Change in Visceral Adiposity | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 PROMIS Fatigue Questionnaire Score | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 | Baseline (Week 0), End of Treatment (Week 12) | 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 | End of Treatment (Week 12) | 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. |
| Percent Change in Body Mass Index (BMI) Z-Score | Baseline (Week 0), End of Treatment (Week 12) | 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. |
Countries
United States
Participant flow
Pre-assignment details
40 participants were enrolled, 15 of them screenfailed. 25 participants were randomized.
Participants by arm
| Arm | Count |
|---|---|
| IMM-124E Group Participants with nonalcoholic fatty liver disease (NAFLD) will receive 600mg of IMM-124E powder three times daily for twelve weeks.
IMM-124E: IMM-124E is a hyper-immune, bovine colostrum (milk) powder with flavoring. | 12 |
| Placebo Group Participants with nonalcoholic fatty liver disease (NAFLD) will receive placebo powder three times daily for twelve weeks.
Placebo: Matched Placebo | 13 |
| Total | 25 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 2 |
Baseline characteristics
| Characteristic | IMM-124E Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 12 Participants | 13 Participants | 25 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) White | 10 Participants | 7 Participants | 17 Participants |
| Region of Enrollment United States | 12 participants | 13 participants | 25 participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 7 Participants |
| Sex: Female, Male Male | 9 Participants | 9 Participants | 18 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 12 | 0 / 13 |
| other Total, other adverse events | 8 / 12 | 10 / 13 |
| serious Total, serious adverse events | 0 / 12 | 0 / 13 |
Outcome results
Primary
Percent Change in Alanine Aminotransferase (ALT) Level
Percent change in ALT level from baseline to end of treatment.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in Alanine Aminotransferase (ALT) Level | 11.99 percentage change | Standard Deviation 25.87 |
| Placebo Group | Percent Change in Alanine Aminotransferase (ALT) Level | -7.99 percentage change | Standard Deviation 16.54 |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
Population: Data were not analyzed due to funding limitation.
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
Population: Data were not analyzed due to funding limitation.
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
Population: Data were not collected. Hemoglobin A1c was only used as a screening lab, it was not measured throughout the study - change cannot be measured
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
Population: Data were not analyzed due to funding limitation.
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
Population: Data were not analyzed due to funding limitation.
Secondary
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.
Time frame: End of Treatment (Week 12)
Population: Data were not analyzed due to funding limitation.
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMM-124E Group | Percent Change in Blood Glucose Level | 2.11 percentage change |
| Placebo Group | Percent Change in Blood Glucose Level | 1.16 percentage change |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMM-124E Group | Percent Change in Body Mass Index (BMI) Z-Score | 1.66 percentage change |
| Placebo Group | Percent Change in Body Mass Index (BMI) Z-Score | -0.48 percentage change |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMM-124E Group | Percent Change in Fasting Glucose Level | 4.55 percentage change |
| Placebo Group | Percent Change in Fasting Glucose Level | 1.11 percentage change |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in Hepatic Fat Percent | -5.70 percentage change | Standard Deviation 16.8 |
| Placebo Group | Percent Change in Hepatic Fat Percent | -6.61 percentage change | Standard Deviation 17.15 |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in PROMIS Anxiety Questionnaire Score | -13.78 percentage change | Standard Deviation 16.39 |
| Placebo Group | Percent Change in PROMIS Anxiety Questionnaire Score | -4.89 percentage change | Standard Deviation 13.89 |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in PROMIS Depression Questionnaire Score | -7.68 percentage change | Standard Deviation 17 |
| Placebo Group | Percent Change in PROMIS Depression Questionnaire Score | 3.62 percentage change | Standard Deviation 11.97 |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in PROMIS Fatigue Questionnaire Score | -10.17 percentage change | Standard Deviation 14.9 |
| Placebo Group | Percent Change in PROMIS Fatigue Questionnaire Score | -4.67 percentage change | Standard Deviation 17.18 |
Secondary
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.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| IMM-124E Group | Percent Change in Visceral Adiposity | 1.23 percentage change | Standard Deviation 8.63 |
| Placebo Group | Percent Change in Visceral Adiposity | 1.77 percentage change | Standard Deviation 9.07 |
Secondary
Percent Change in Waist Circumference
Waist circumference will be measured in centimeters using measuring tape.
Time frame: Baseline (Week 0), End of Treatment (Week 12)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| IMM-124E Group | Percent Change in Waist Circumference | 2.29 percentage change |
| Placebo Group | Percent Change in Waist Circumference | 0.76 percentage change |