Amino Acids for Fatty Liver Disease

(AMINOS Trial)

Overseen By Yesenia Garcia Reyes, MS

Age: < 65

Sex: Any

Trial Phase: Phase 3

Sponsor: University of Colorado, Denver

Must not be taking: Metformin, Glucocorticoids, Antipsychotics, others

Disqualifiers: Pregnancy, Diabetes, Anemia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 8 weeks

55 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Participants 13-18 years of age with extra fat stored in the liver will be randomly assigned to a protein supplement or placebo "fake supplement" for 2 months to see if the participants who get the protein supplement have less fat in the liver compared to participants who were in the placebo group. After the 2 month intervention, all participants can continue the study and will all receive the protein supplement for an additional 10-months.

Will I have to stop taking my current medications?

The trial requires that you do not take certain medications that affect insulin sensitivity, like metformin, or blood pressure medications. If you are on these, you may need to stop them to participate.

Is the Essential Amino Acid Supplement safe for humans?

Research on branched-chain amino acids (BCAAs), a type of amino acid supplement, shows they do not cause adverse effects in patients with liver conditions, suggesting they are generally safe for human use. ^{1 2 3 4 5}

How is the Essential Amino Acid Supplement treatment different from other treatments for fatty liver disease?

The Essential Amino Acid Supplement by Amino Co is unique because it uses a specific combination of amino acids that target multiple aspects of nonalcoholic steatohepatitis (NASH), including metabolism, inflammation, and fibrosis, which are core features of the disease. This multitargeted approach is different from other treatments that may focus on only one aspect of the condition. ^{1 3 5 6 7}

What data supports the effectiveness of the treatment Essential Amino Acid Supplement by Amino Co for fatty liver disease?

Research on a combination of amino acids similar to those in the supplement showed potential benefits in treating nonalcoholic steatohepatitis (a severe form of fatty liver disease) by impacting metabolism, inflammation, and fibrosis in cell models. This suggests that specific amino acid combinations might help manage fatty liver disease. ^{1 3 8 9 10}

Who Is on the Research Team?

Melanie Cree, MD, PhD

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

Adolescents aged 13-18 with fatty liver disease, specifically non-alcoholic fatty liver disease (NAFLD), who are overweight and do not exercise much. They must have a confirmed diagnosis by biopsy and be in the later stages of puberty. Those who are very active or don't meet the specific medical criteria cannot join.

Inclusion Criteria

Sedentary- less than 3 hours of moderate (jogging, swimming, etc.) exercise a week

I am between 13 and 18 years old and have advanced in puberty.

My BMI is in the overweight or obese range for my age and gender.

Exclusion Criteria

Implanted metal devices that are not compatible with MRI

I am taking medication for high blood pressure.

Currently pregnant or breastfeeding women. Development of pregnancy during the study period will necessitate withdrawal from the study

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to receive either a protein supplement or placebo for 2 months

8 weeks

2 visits (in-person) for MRI, body x-ray, and blood draw

Open-label extension

All participants receive the protein supplement for an additional 10 months

10 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Essential Amino Acid Supplement by Amino Co

Trial Overview The study is testing if an essential amino acid supplement can reduce liver fat in teens with NAFLD compared to a placebo over two months. After this period, all participants will receive the actual supplement for ten more months.

How Is the Trial Designed?

Group I: Amino Acid Supplement Active Control 1 Intervention

Participants are blindly randomized and for this arm, participants will take the Essential Amino Acid Supplement for 2-months, followed by an open label extension period of 10-months of Essential Amino Acid for all participants

Group II: Placebo Placebo Group 1 Intervention

Participants are blindly randomized and for this arm, participants will take the Placebo for 2-months, followed by an open label extension period of 10-months of Essential Amino Acid for all participants

Essential Amino Acid Supplement by Amino Co is already approved in United States for the following indications:

Approved in United States as Essential Amino Acid Supplement for:

• Nutritional supplement for general health and wellness

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 122 patients who underwent pancreaticoduodenectomy, early administration of high-titer pancrelipase and a branched-chain amino acid (BCAA) diet starting on postoperative day 4 significantly improved liver function and nutritional status compared to a control group.

Patients receiving the pancrelipase and BCAA diet showed better liver attenuation and lower alanine aminotransferase levels, indicating a reduced risk of nonalcoholic fatty liver disease (NAFLD) after surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pancrelipase with branched-chain amino acids for preventing nonalcoholic fatty liver disease after pancreaticoduodenectomy. Yamazaki, S., Takayama, T., Higaki, T., et al.[2019]

In a study of 64 patients with acute alcoholic hepatitis, providing additional nitrogen through diet supplementation did not significantly improve nutritional outcomes or reduce mortality compared to a controlled diet alone.

Neither enteral nor parenteral branched chain amino acids had a consistent effect on encephalopathy, indicating that these treatments may not be effective in managing this condition in patients with liver dysfunction.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. Calvey, H., Davis, M., Williams, R.[2022]

A novel composition of endogenous metabolic modulators (EMMs) consisting of five amino acids and an amino acid derivative (LIVRQNac) was systematically evaluated in various human cell models relevant to nonalcoholic steatohepatitis (NASH), showing significant effects on metabolic, inflammatory, and fibrotic aspects of the disease.

The study found that while individual amino acids had some effects on NASH-related issues, the complete combination of LIVRQNac was essential for addressing the full range of disease mechanisms, suggesting that multitargeted interventions may be more effective for treating complex metabolic diseases like NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models. Daou, N., Viader, A., Cokol, M., et al.[2021]

In a study of 91 patients with alcoholic liver cirrhosis, a late evening snack (LES) combined with oral amino acid (OAA) capsules significantly improved energy metabolism, as indicated by higher respiratory quotient (RQ) values compared to the LES alone and control groups.

The combination of LES and OAA not only increased serum isoleucine levels but also improved the Fischer ratio, suggesting enhanced nutritional support and metabolic function in ALC patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late evening snack and oral amino acid capsules improved respiratory quotient and Fischer ratio in patients with alcoholic liver cirrhosis. Zhao, J., Wu, J., Li, J., et al.[2023]

In a study involving 50 obese patients with non-alcoholic fatty liver disease (NAFLD), alpha-lipoic acid (ALA) supplementation significantly reduced serum levels of the inflammatory marker IL-6 and increased adiponectin levels after 12 weeks.

Despite these positive changes in inflammatory markers, ALA supplementation did not lead to significant differences in liver enzymes or liver steatosis compared to the placebo group, indicating that while ALA may have some benefits, it does not appear to improve liver fat content in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. Hosseinpour-Arjmand, S., Amirkhizi, F., Ebrahimi-Mameghani, M.[2019]

In a study of 124 patients with advanced liver disease, long-term oral supplementation of branched-chain amino acids (BCAAs) significantly improved liver function as indicated by better MELD and Child-Pugh scores compared to a control group.

BCAA supplementation also led to a significant increase in event-free survival over 24 months, suggesting it may help reduce major complications associated with cirrhosis, despite no improvement in serum albumin and bilirubin levels.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study. Park, JG., Tak, WY., Park, SY., et al.[2021]

Oral branched-chain amino acid (BCAA) supplements significantly improve symptoms of hepatic encephalopathy (HE) in patients with cirrhosis, with a risk ratio of 1.71, indicating that for every 5 patients treated, one will benefit from the treatment.

While BCAAs help alleviate HE symptoms, they do not affect mortality rates or nutritional status, and they are safe with no reported adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. Gluud, LL., Dam, G., Borre, M., et al.[2023]

A study involving 225 newly diagnosed NAFLD patients and 450 controls found that higher dietary intake of branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), and sulfuric amino acids (SAAs) is associated with increased odds of developing nonalcoholic fatty liver disease (NAFLD).

Specifically, participants in the highest tertiles of amino acid intake had odds ratios of 2.82 for BCAAs and AAAs, and 2.86 for SAAs, indicating a significant link between these amino acids and NAFLD risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The association between dietary amino acids and the risk of nonalcoholic fatty liver disease among Tehranian adults: a case-control study. Mokhtari, E., Ahmadirad, H., Teymoori, F., et al.[2023]

In a study of 54 patients with severe alcoholic hepatitis, those receiving parenteral amino acids showed improved nitrogen balance and better liver function markers, such as serum bilirubin and prothrombin time, compared to those receiving only dextrose.

Despite these improvements, the 2-year survival rates were similar between the treatment group (42%) and the control group (38%), indicating that while amino acid treatment may enhance certain health parameters, it did not significantly impact overall mortality in this patient population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial. Mezey, E., Caballería, J., Mitchell, MC., et al.[2022]

In a study of 137 patients with nonalcoholic fatty liver disease, lower levels of branched-chain amino acids (BCAAs) were associated with more advanced liver fibrosis, while higher levels of tyrosine correlated with increased fibrosis stages.

The findings suggest a complex relationship between amino acid imbalance and insulin resistance in nonalcoholic steatohepatitis (NASH), indicating that monitoring these amino acids could be important for understanding disease progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease. Kawanaka, M., Nishino, K., Oka, T., et al.[2020]

Citations

1. Japan pubmed.ncbi.nlm.nih.gov

Pancrelipase with branched-chain amino acids for preventing nonalcoholic fatty liver disease after pancreaticoduodenectomy. [2019]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Controlled trial of nutritional supplementation, with and without branched chain amino acid enrichment, in treatment of acute alcoholic hepatitis. [2022]

3. England pubmed.ncbi.nlm.nih.gov

A novel, multitargeted endogenous metabolic modulator composition impacts metabolism, inflammation, and fibrosis in nonalcoholic steatohepatitis-relevant primary human cell models. [2021]

4. Mexico pubmed.ncbi.nlm.nih.gov

Late evening snack and oral amino acid capsules improved respiratory quotient and Fischer ratio in patients with alcoholic liver cirrhosis. [2023]

5. England pubmed.ncbi.nlm.nih.gov

The effect of alpha-lipoic acid on inflammatory markers and body composition in obese patients with non-alcoholic fatty liver disease: A randomized, double-blind, placebo-controlled trial. [2019]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Effects of Branched-Chain Amino Acid (BCAA) Supplementation on the Progression of Advanced Liver Disease: A Korean Nationwide, Multicenter, Prospective, Observational, Cohort Study. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Oral branched-chain amino acids have a beneficial effect on manifestations of hepatic encephalopathy in a systematic review with meta-analyses of randomized controlled trials. [2023]

8. England pubmed.ncbi.nlm.nih.gov

The association between dietary amino acids and the risk of nonalcoholic fatty liver disease among Tehranian adults: a case-control study. [2023]

9. United States pubmed.ncbi.nlm.nih.gov

Effect of parenteral amino acid supplementation on short-term and long-term outcomes in severe alcoholic hepatitis: a randomized controlled trial. [2022]

10. New Zealand pubmed.ncbi.nlm.nih.gov

Tyrosine levels are associated with insulin resistance in patients with nonalcoholic fatty liver disease. [2020]