Paso Program for Fatty Liver Disease

Overseen By Maya Balakrishnan, MD MPH

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Baylor College of Medicine

Must not be taking: SGLT2 inhibitors, GLP-1 agonists

Disqualifiers: Advanced liver disease, Organ transplant, Heavy alcohol use, Active cancer, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 4

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to evaluate the effectiveness of the Paso Program, a weight loss program for Mexican and Central American patients with fatty liver disease. Researchers are examining the program's impact on weight loss, liver health, physical activity, diet, and family support. The trial seeks participants with fatty liver disease and at least one metabolic syndrome feature, such as high blood sugar or cholesterol, who identify as Mexican or Central American. Participants should also have a BMI over 25 and be able to read and write in English or Spanish. As an unphased trial, this study offers a unique opportunity to contribute to understanding how lifestyle changes can improve health outcomes in this specific community.

Will I have to stop taking my current medications?

The trial does not specify if you must stop taking your current medications. However, if you are on SGLT2 inhibitors or GLP-1 agonists, you must be on a stable dose for at least 6 months before joining the study. Pioglitazone is allowed if you have been on a stable dose for 3 months prior to the study.

What prior data suggests that the Paso Program is safe for patients with fatty liver disease?

Research has shown that weight loss programs like the Paso Program are generally safe for individuals with nonalcoholic fatty liver disease. These programs emphasize lifestyle changes, such as diet and exercise, which most participants manage well. Although the Paso Program is new and lacks specific safety data, similar programs have not revealed major safety concerns. Since this program involves behavior changes rather than medication, the risk of serious side effects remains low. Participants in weight loss programs typically experience improved liver health and overall well-being without significant negative effects. ^{1 2 3 4 5}

Why are researchers excited about this trial?

The Paso Program is unique because it takes a behavioral approach to treating fatty liver disease, focusing on weight loss through lifestyle changes. Unlike traditional treatments that may rely on medication, this program emphasizes sustainable habits and education to promote liver health. Researchers are excited because this method could empower patients to manage their condition more effectively and safely, without the side effects often associated with pharmaceuticals.

What evidence suggests that the Paso Program is effective for fatty liver disease?

Research shows that weight loss programs can help manage non-alcoholic fatty liver disease (NAFLD). This condition occurs when fat accumulates in the liver, potentially leading to serious health issues. Studies have found that losing weight can reduce liver fat, enhance liver function, and might even repair damage. In this trial, all participants will receive the Paso Program, a weight loss plan designed to aid weight loss and improve liver health. Previous studies on similar programs have shown promising results in reducing liver fat and boosting overall health in people with NAFLD. ^{3 6 7 8 9}

Who Is on the Research Team?

Maya Balakrishnan

Principal Investigator

Baylor College of Medicine

Are You a Good Fit for This Trial?

This trial is for Mexican & Central American individuals with fatty liver disease linked to metabolic dysfunction, such as being overweight or having diabetes. It aims to see if the Paso weight loss program can help them.

Inclusion Criteria

Self-reported Mexican or Central American ethnicity

BMI≥25kg/m2

I have been diagnosed with MASLD, showing liver fat and a metabolic condition.

Exclusion Criteria

History of noncompliance (>3 primary care, endocrine, and/or hepatology clinic no-shows in the past year)

I have an active hepatitis infection or another chronic liver disease.

My HbA1c level is 9.0% or higher.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants engage in the Paso weight loss program, consisting of 16 1-hour group counseling classes over 6 months, focusing on healthy eating, physical activity, and behavioral strategies.

6 months

4 in-person classes, remaining classes can be attended in-person or virtually

Follow-up

Participants are monitored for changes in weight, liver health, and other health metrics at 4 time points over 1 year, including 6 months after the program ends.

6 months

Regular clinic visits, program sessions, or phone assessments

What Are the Treatments Tested in This Trial?

Interventions

• Paso Program

Trial Overview The study tests the feasibility of the Paso Program—a weight loss initiative—on improving health outcomes like fatty liver disease, physical activity levels, diet quality, and family support in participants.

How Is the Trial Designed?

Group I: Intervention Arm Experimental Treatment 1 Intervention

All participants will receive the intervention, which is a behavioral weight loss program called "Paso a Paso: Rumbo a Un Higado Sano" ("Paso Program").

Who Is Running the Clinical Trial?

Baylor College of Medicine

Lead Sponsor

Trials

1,044

Recruited

6,031,000+

National Institute on Minority Health and Health Disparities (NIMHD)

Collaborator

Trials

473

Recruited

1,374,000+

Published Research Related to This Trial

A weight reduction program is the most effective treatment for non-alcoholic fatty liver disease (NAFLD), preventing cirrhosis and hepatocellular carcinoma (HCC) cases by 13.91% and 2.12%, respectively, while also being the most cost-effective option in Thailand.

Pioglitazone and vitamin E showed some potential in reducing cirrhosis and HCC cases, but their effectiveness and cost-effectiveness were significantly lower compared to the weight reduction program, which had a 76% probability of being cost-effective.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight Reduction and Pioglitazone are Cost-Effective for the Treatment of Non-Alcoholic Fatty Liver Disease in Thailand. Chongmelaxme, B., Phisalprapa, P., Sawangjit, R., et al.[2020]

A multidisciplinary clinical program for children with nonalcoholic fatty liver disease (NAFLD) led to significant improvements in weight-related outcomes, including a decrease in BMI z score and liver enzyme levels after one year.

Out of 108 enrolled children, 39 showed notable reductions in cholesterol and liver enzymes, indicating that structured dietary and exercise advice can effectively manage NAFLD in a gastroenterology setting.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A multidisciplinary clinical program is effective in stabilizing BMI and reducing transaminase levels in pediatric patients with NAFLD. DeVore, S., Kohli, R., Lake, K., et al.[2021]

Nonalcoholic fatty liver disease (NAFLD) is increasingly common, particularly among individuals with metabolic syndrome, and poses serious health risks including liver fibrosis, cirrhosis, and cardiovascular disease.

The review emphasizes the need for screening programs in high-prevalence areas, discussing the effectiveness and methods for screening, as well as who should be targeted and responsible for these screenings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Screening for nonalcoholic fatty liver disease-when, who and how? Dietrich, CG., Rau, M., Geier, A.[2021]

In a randomized, double-blind, placebo-controlled trial involving 99 patients with non-alcoholic fatty liver disease (NAFLD), the Tiaogan Lipi Recipe (TLR) combined with lifestyle changes significantly improved clinical symptoms and liver function compared to a placebo after 12 weeks.

The treatment group showed greater reductions in liver enzymes (ALT, AST, GGT) and better overall liver/spleen CT ratios, indicating effective liver protection and anti-inflammatory effects, with a total effective rate of 79.69% for TLR compared to 56.25% for the placebo group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Treating non-alcoholic fatty liver disease patients of Gan stagnation Pi deficiency syndrome by tiaogan lidi recipe: a randomized controlled clinical trial]. Yu, Q., Zhang, SS., Zhou, T., et al.[2018]

Non-alcoholic fatty liver disease (NAFLD) affects 20-30% of the general population and can progress to serious liver conditions, highlighting the need for effective detection and treatment strategies.

A multidisciplinary approach is essential for managing NAFLD, with early-stage patients being treated in Primary Care and those with advanced disease requiring specialized hospital care, supported by non-invasive diagnostic methods and management algorithms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recommendations for the detection, diagnosis and follow-up of patients with non-alcoholic fatty liver disease in primary and hospital care. Caballeria, L., Augustin, S., Broquetas, T., et al.[2020]

Using a combination of FIB-4 and shear wave elastography (SWE) is the most cost-effective method for correctly diagnosing significant fibrosis (≥F2) in patients with non-alcoholic fatty liver disease (NAFLD), costing $148.75 per correct diagnosis and achieving an 84% accuracy rate.

For advanced fibrosis (≥F3), the FIB-4 followed by SWE strategy not only identified 92% of cases correctly but also proved to be the least expensive option, highlighting its effectiveness in managing high-risk NAFLD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modelling the cost effectiveness of non-alcoholic fatty liver disease risk stratification strategies in the community setting. Congly, SE., Shaheen, AA., Swain, MG.[2021]

Nonalcoholic fatty liver disease (NAFLD) affects up to 25% of adults globally and is closely linked to rising rates of obesity and type 2 diabetes, leading to increased liver complications like non-alcoholic steatohepatitis (NASH) and cirrhosis.

NAFLD not only raises the risk of liver-related health issues but also significantly increases the likelihood of developing serious conditions such as cardiovascular disease, extra-hepatic cancers, and chronic kidney disease, contributing to a substantial global health burden.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complications, morbidity and mortality of nonalcoholic fatty liver disease. Mantovani, A., Scorletti, E., Mosca, A., et al.[2020]

Current treatments for nonalcoholic fatty liver disease (NAFLD) are still not very effective, but weight loss remains a key target for therapy despite being difficult to achieve.

Several investigational drugs show promise for treating NASH, but concerns about long-term safety exist, particularly with vitamin E and other medications like pioglitazone and obeticholic acid, which have notable side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment options for nonalcoholic steatohepatitis - a safety evaluation. Issa, D., Wattacheril, J., Sanyal, AJ.[2017]

In a phase 2 trial involving 140 patients with nonalcoholic steatohepatitis (NASH), cilofexor 100 mg daily for 24 weeks significantly reduced liver fat content by 22.7% compared to a placebo, indicating its efficacy in treating hepatic steatosis.

Cilofexor was generally well-tolerated, although moderate to severe itching was reported more frequently in the 100 mg group (14%) compared to the lower dose and placebo, suggesting a manageable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cilofexor, a Nonsteroidal FXR Agonist, in Patients With Noncirrhotic NASH: A Phase 2 Randomized Controlled Trial. Patel, K., Harrison, SA., Elkhashab, M., et al.[2021]

In a systematic review of 10 studies involving patients with non-alcoholic fatty liver disease (NAFLD) or non-alcoholic steatohepatitis (NASH), treatment with 4 mg saroglitazar significantly reduced liver enzymes, including alanine transaminase (ALT) and aspartate transaminase (AST), indicating improved liver function.

Saroglitazar also led to significant improvements in liver stiffness and metabolic parameters such as glycated hemoglobin, total cholesterol, and triglycerides, suggesting it is an effective and safe treatment option for managing NAFLD and NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of saroglitazar in the treatment of non-alcoholic fatty liver disease or non-alcoholic steatohepatitis: A systematic review and meta-analysis. Bandyopadhyay, S., Samajdar, SS., Das, S.[2023]

A Markov model was developed to predict long-term outcomes for nonalcoholic steatohepatitis (NASH) treatments, showing that higher baseline fibrosis stages significantly increase the risk of liver-related complications over 10 years.

The model indicated that a treatment profile focused on reducing fibrosis worsening had the most substantial impact on lowering long-term complication rates, suggesting that managing fibrosis progression is crucial in NASH treatment strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of emerging NASH therapies: the impact of treatment efficacy profiles on long-term health outcomes. Herring, WL., Gould, IG., Wittrup-Jensen, V., et al.[2023]

In a study of 70 severely obese patients who underwent laparoscopic weight loss surgery, significant improvements in liver health were observed, including a reduction in liver fat from 88% to 8% and a decrease in liver inflammation and fibrosis.

The surgery also led to a dramatic decrease in the prevalence of metabolic syndrome, from 70% to 14%, suggesting that weight loss surgery not only improves liver conditions but may also reverse associated metabolic issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgically-induced weight loss significantly improves nonalcoholic fatty liver disease and the metabolic syndrome. Mattar, SG., Velcu, LM., Rabinovitz, M., et al.[2022]

In a meta-analysis of 41 randomized controlled trials involving 2,944 participants with non-alcoholic steatohepatitis (NASH), 68% of those on placebo experienced at least one adverse event (AE), highlighting the need for careful safety evaluations in this largely asymptomatic condition.

Serious adverse events were reported in 7.8% of placebo participants, with a notably higher incidence in phase 3 trials and those funded by pharmaceutical companies, indicating that the context of the study may influence safety outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Placebo Adverse Events in Non-alcoholic Steatohepatitis Clinical Trials: A Pooled Analysis of 2,944 Participants. Tay, PWL., Ng, CH., Lin, SY., et al.[2023]

Citations

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Non-alcoholic fatty liver disease: when to intervene and ... Introduction. Non-alcoholic fatty liver disease (NAFLD), defined as accumulation of fat in the liver in the absence of excessive alcohol consumption, is now ...

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Long-Term Outcomes of Nonalcoholic Fatty Liver Disease Long-term outcomes of nonalcoholic fatty liver disease: from nonalcoholic steatohepatitis to nonalcoholic steatofibrosis.

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FEASIBILITY OF THE "PASO A PASO" WEIGHT LOSS ... The purpose of this study is to learn whether the program is feasible for Mexican and Central American patients with fatty liver disease. In ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7724182/

Basic science to clinical trials in non-alcoholic fatty liver ... More importantly, there was improvement in hepatic steatosis on MRI-PDFF that was dose dependent with 39%, 14%, 12.5% of patients achieving ≥30% decline in fat ...

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Associations of Unhealthy Lifestyle and Nonalcoholic Fatty ... Nonalcoholic fatty liver disease (NAFLD) acts as a mediating factor in the associations between various lifestyles (diet habits, physical ...

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Nonalcoholic Fatty Liver Disease 2020: The State of ... Liver fibrosis, but no other histologic features, is associated with long-term outcomes of patients with nonalcoholic fatty liver disease.