The Influence of Probiotics on Metabolome and Heart Rate Variability in Heart Failure of Structure Heart Disease

NCT06872320 | Active Not Recruiting

• 1 other identifier: 202301449A3
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Poor body weight gain and failure to thrive is a very common condition in patients with congenital heart disease (CHD) with advanced HF and/or cyanosis, which are considered a predictor of morbidity and complicate the prognosis of CHD. Studies have been carried out an attempt to discover the mechanisms to improve the therapies and the prognosis of these patients. Some of these studies give the hypothesis that the gastrointestinal tract, more precisely the intestine, can collaborate with metabolome. Extra-intracardiac shunt and HF lead to hypoperfusion and cyanotic heart disease leads to hypoxia. These two conditions make the gastrointestinal tract of these patients to become more mal-absorption to food. Consequently, the poor intestinal microcirculation and resultant dysbiosis may contribute to poor body weight gain and the worsening of prognosis. As known, probiotics can help to maintain or recover the microbiota and maintain a healthy intestinal barrier. In view of the importance of microbiota to the metabolism and the possible beneficial effect in the prognosis of heart-failure patients and the performance of microbiota in maintenance of intestinal barrier, this study has as primary objective to verify the influence of supplementation of the probiotic Lactobacillus Rhamnosus in the patients with CHD. Malabsorption and dysbiosis in patients with CHD Poor body weight gain and failure to thrive is a very common condition in patients with congenital heart disease (CHD). Dysbiosis occurs in patients with CHD. Such dysbiosis and intestinal barrier dysfunction may become worsen after they underwent cardiopulmonary bypass, and complicate the prognosis of CHD. Probiotics and Metabolome in Heart failure Cumulative evidence shows increasing importance of microbiota and cardiovascular disease and health. Metabolomic changes are found in CHD patients with hypoxia. It is suggested that Lactobacillus strains function to promote cardiovascular-related conditions. However, the effect of probiotic administration on CHD remains controversial. The investigators propose that hypothesis that Lactobacillus Rhamnosus directly improve the body weight gain and indirectly improve the outcome of patients with CHD. Accordingly, the investigators initiate this clinical trial to testify the beneficial effect of Lactobacillus Rhamnosus on CHD.

Conditions

Congenital Heart Disease; Dysbiosis; Malnutrition, Child; Probiotics; Metabolome

Outcome Measures

Primary Outcomes (1)

• Percentile of body weight gain

  The difference of body weight percentile from the enrollment as the base line to the end of 24-wk treatment (Body weight percentile will be calculated according to the Taiwan children growth reference：https://growth.healthinfo.tw )

  From enrollment to the end of treatment an average of 24 weeks.

Secondary Outcomes (3)

• Decrease of cardiac chamber enlargement.

  The difference of following measurements from the enrollment as the base line to the end of 24-wk treatment

• The cardiac function

  The difference of following measurements from the enrollment as the base line to the end of 24-wk treatment

• Serum NT-proBNP leve

  The difference of following measurements from the enrollment as the base line to the end of 24-wk treatment

Other Outcomes (1)

• Circulating levels of proinflammatory cytokines

  The difference of following measurements from the enrollment as the base line to the end of 24-wk treatment

Study Arms (2)

Lactobacillus Rhamnosus

ACTIVE COMPARATOR

Lactobacillus Rhamnosus (More than 1 billion colonies), Maltodextrin, Magnesium Stearate

Drug: Placebo

placebo

PLACEBO COMPARATOR

Maltodextrin, Magnesium Stearate

Drug: Lactobacillus Rhamnosus

Interventions

Lactobacillus Rhamnosus DRUG

Lactobacillus Rhamnosus (Lactobacillus Rhamnosus, MoProbi-LR Capsules, Drug permit license 052531); Age \< 2 years old: 1/2 capsule once daily for 24 weeks per oral Age ≥ 2 years old: 1 capsule once daily for 24 weeks per oral

placebo

Placebo DRUG

Maltodextrin comparable in color. Age \< 2 years old: 1/2 capsule once daily for 24 weeks per oral Age ≥ 2 years old: 1 capsule once daily for 24 weeks per oral

Lactobacillus Rhamnosus

Eligibility Criteria

• Age: 1 Month - 3 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Patients at ages ≤ 3 years old with congenital structure/valvular heart disease and cardiomyopathy with varying degrees of HF NYHA/ROSS functional class and ejection fraction ≥ 35% by echocardiography at the entry of study;
• No recent 1-month hospitalizations for HF decompensated;
• Have signed the Free and Informed Consent Form.

You may not qualify if:

• CHD with NYHA functional class IV or ejection fraction \< 35%;
• Do not accept to participate in the study or do not sign the Free and Informed Consent Form;
• Have used antibiotics and/or corticosteroids and/or other formula containing probiotics in the last 30 days prior enrollment;
• Clinical conditions that can affect the inflammatory profile such as inflammatory bowel disease, arthrosis, among others;
• Chronic severe diarrhea (\> 2 weeks; \> 5 times/day) in the last 3 months;
• Have been submitted to a cardiac surgery or other surgery in the last 3 months;
• Severe lactose intolerance;
• Profound anemia (WBC\> 15000, Hb\< 8 ) or hematologic disorder, severe hepatic dysfunction (GPT\> 100), renal function (Cr\> 1.5), abnormal stool analysis or active infection status (CRP\> 10).

Sponsors & Collaborators

• Chang Gung Memorial Hospital: lead

Study Sites (1)

Kaohsiung Chang Gung Memorial Hospital and Chang Gung University

Kaohsiung City, Taiwan

Location

MeSH Terms

Conditions

Heart Defects, Congenital; Dysbiosis; Child Nutrition Disorders

Condition Hierarchy (Ancestors)

Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Nutrition Disorders; Nutritional and Metabolic Diseases

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Second arm: 1. Serum NT-proBNP level: more than 25% decline of the level at entrySerum NT-proBNP level: more than 25% decline of the level at entry. 2. The size of cardiac chambers, cardiac function, and shunt by echocardiography; 3. Circulating levels of proinflammatory cytokines- TNF-α, IL-6, and IL-10 by multiplex immunoassay; 4. Metabolomics study for heart failure patients with and without end-point improvement.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: One arm: participants will be stratified into two stratum and then assigned to one of the following double-blind treatment in a ratio of 2:1 at the randomization.

Study Record Dates

• First Submitted: November 28, 2024
• First Posted: March 12, 2025
• Study Start: March 28, 2025
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 22, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

TW (1)