Probiotics and Inflammatory Status in Patients With Heart Failure (PROBHF)

Study of the Importance of Intestinal Microbiota in Patients With Heart Failure - Randomized, Double-blind Study

Cachexia is a very common condition in patients with advanced heart failure (HF) and is considered a predictor of mortality. Studies have been carried out in an attempt to discover the mechanisms that leads to cachexia in order to improve the therapies and the survival of these patients. Some of these studies give the hypothesis that the gastrointestinal tract, more precisely the intestine, can collaborate with cachexia. Some of these studies suggest that, the intestinal mucosa, due to hypoperfusion, becomes more permeable to some substances, as like endotoxins, being the lipopolysaccharide (LPS) one of them. The circulating LPS can stimulate the increase of tumor necrosis alpha (TNF-alpha) further increasing the inflammation and, consequently, contributing to the worsening of prognosis. The intestinal microbiota is also affected by hypoperfusion, contributing with increase of permeability. 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 inflammation in the prognosis of the 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 acidophilus (LA) in the lowering of serum levels of TNF-alpha in the patients with HF.

Study Overview

• Status: Unknown
• Conditions: Heart Failure
• Intervention / Treatment: Other: Placebo; Dietary supplement: Probiotic

Detailed Description

The present study will be a clinical trial compounded by two parallel arms, randomized, double-blind (researcher-patient), placebo-controlled, with patients with heart failure (HF), functional class according the New York Heart Association (NYHA) III and IV. It will be included 58 patients, 29 will receive probiotics and 29 will receive placebo. These patients will be accompanied during 6 months and should take one capsule every day during the study. In the beginning of the study and at the end, venous blood sample will be collected of each patient for laboratory measurement of TNF alpha, interleukins 1,6 and 10, LPS, B-type natriuretic peptide (BNP) and C-reactive protein (CRP). To establish the normality pattern of these markers studied, a control group, with healthy individuals, will be performed.An anthropometric evaluation will be performed with measurements of weigh, height, arm circumference, triceps skin fold. According to nutritional status, it will be calculated the caloric and protein needs of each patient and, to monitor the consumption, in each consult will be applied the 24-hour food recall and calculated the consumption from it. In order to measure the appetite of the patients, in each consult, an appetite questionnaire will be applied. To statistical analysis, the test of Kolmogorov-Smirnov will be used to assess whether the distribution is normal for the quantitative variables. If the variable follows normal distribution, it will be described as mean and standard deviation, otherwise, it will be described as median and interquartile range. The groups will be compared using t-Student or Mann-Whitney tests. The categorical variables will be presented descriptively with absolute and relative frequencies. The association between categorical variables will be analyzed with chi square test or Fisher exact test or likelihood ratio test. For the repeated measures, will be used the ANOVA test or Friedman test and Wilcoxon signs. The analyzes will be performed according to the intent-to-treat principle and the two-tailed tests. The value of p<0,5 will be considered statistically significant.

• Study Type: Interventional
• Enrollment (Anticipated): 58
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fernando Bacal, MD PhD; Phone Number: (11) 2661-5482; Email: fbacal@uol.com.br

Study Locations

• Brazil
  • São Paulo, Brazil
    • Recruiting
    • Fernando Bacal
    • Contact: Fernando Bacal; Phone Number: (11) 2661-5482; Email: fbacal@uol.com.br

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Patients with heart failure NYHA functional class III and IV;
• Medications optimized for at least 2 months;
• No hospitalizations for HF decompensated or acute myocardial infarction in the last 30 days;
• Have signed the Free and Informed Consent Form

Exclusion Criteria:

• Do not accept to participate in the study or do not signed the Free and Informed Consent Form
• Have used antibiotics and/or corticosteroids in the last 30 days;
• Clinical conditions that can affect the inflammatory profile such as inflammatory bowel disease, arthrosis, among others;
• Be pregnant;
• Have been submitted to a cardiac surgery in the last 6 months or other surgery in the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; These patients will receive capsules containing vegetable oil and corn starch	Other: Placebo; Those patients in group Placebo will receive the capsules containing vegetable oil and corn starch and will need to take one of it everyday during the study.
Active Comparator: Probiotic; These patients will receive capsules containing Lactobacillus acidophilus	Dietary supplement: Probiotic; Those patients in group Probiotic will receive the capsules containing Lactobacillus acidophilus and will need to take one of it everyday during the study.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of probiotics in serum levels of TNF-alpha	Probiotics should improve serum levels of tumor necrosis alpha (TNF-alpha)	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effects of probiotics in serum levels of lipopolysaccharide LPS (ng/mL)	Probiotics should improve serum levels of LPS (ng/mL)	six months
Effects of probiotics in serum levels of interleukin 1 (IL 1) (pg/mL)	Probiotics should improve serum levels of IL 1 (pg/mL)	six months
Effects of probiotics in serum level of interleukin 6 (IL 6) (pg/mL)	Probiotics should improve serum levels of IL 6 (pg/mL)	six months
Effects of probiotics in serum levels of interleukin 10 (IL 10)(pg/mL)	Probiotics should improve serum levels of IL 10 (pg/mL)	six months
Effects of probiotics in serum levels of B-type natriuretic peptide (BNP) (pg/mL)	Probiotics should improve serum levels of BNP (pg/mL)	six months
Effects of probiotics in serum levels of C-reactive protein (CRP) (mg/L)	Probiotics should improve serum levels of CRP (mg/L)	six months
Effects of probiotics in appetite	Probiotics should improve the appetite	six months

Collaborators and Investigators

• Sponsor: University of Sao Paulo General Hospital
• Collaborators: Fundação de Amparo à Pesquisa do Estado de São Paulo
• Investigators: Principal Investigator: Fernando Bacal, MD PhD, Heart Institute (InCor), University of Sao Paulo, Medical School

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2018
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): August 31, 2020

Study Registration Dates

• First Submitted: November 1, 2018
• First Submitted That Met QC Criteria: May 29, 2019
• First Posted (Actual): May 30, 2019

Study Record Updates

• Last Update Posted (Actual): May 30, 2019
• Last Update Submitted That Met QC Criteria: May 29, 2019
• Last Verified: May 1, 2019

More Information

Terms related to this study

• Keywords: Inflammation; Heart failure; Probiotics; Intestinal microbiota
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: PROBHF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No