Probiotics and Insulin Resistance in Obese Asthmatics

NCT05949255 | Active Not Recruiting

• 2 other identifiers: IRB-300011423ALA 1143197
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

In this pilot study investigators will test the hypothesis that administration of oral probiotics modulates microbiome/metabolome, lowers leptin and insulin resistance and improves clinical parameters of asthma in obese insulin resistant asthmatics. Preliminary studies with oral probiotic administration in obese asthmatics showed increased abundance of probiotics-derived Bifidobacterium species and Bifidobacterium-derived metabolite in the airways of asthmatics. Additionally, neutrophils and IL-17 producing Th17 cells were significantly reduced following probiotics administration. Based on these preliminary studies, the investigators propose to test the following aims: Specific Aim 1: Determine if probiotic administration modulates airway microbiome/metabolome in obese insulin resistant asthmatics Specific Aim 2: Determine if modulation of leptin levels and insulin sensitivity by probiotics administration correlates with airway metabolome alterations and weight loss in obese insulin resistant asthmatics Specific Aim 3: Determine if microbiome/metabolome changes in probiotics group correlates with changes in asthma biomarkers and improved clinical outcomes compared to placebo in obese insulin resistant asthmatics.

Conditions

Asthma; Obesity; Insulin Resistance

Outcome Measures

Primary Outcomes (3)

• Determine if probiotic administration modulates airway microbiome/metabolome in obese insulin resistant asthmatics

  (1a) For airway microbiome analyses, nasal wash samples will be used as surrogates. Nasal wash will be collected from subjects at baseline and 12 weeks. Rectal swab will be collected using Fecal swab kit (COPAN, Thermofisher) and samples prepared for microbiome analysis as above. Microbial genomic DNA from the samples will be isolated using the DNA isolation kit from Zymo Research. (1b) The samples obtained in Aim 1a will be used for metabolomics analyses, both gut and airway samples. Untargeted metabolomics utilizing Liquid Chromatography coupled with mass spectrometry will be performed at UAB Metabolomics Core and metabolites including SCFA, acetate, lactate, ethanol, succinate, formate and enterolactone will be analyzed and quantitated. For both above aims, changes over the 12 weeks will be compared between groups.

  12 weeks

• Determine if modulation of leptin levels and insulin sensitivity by probiotics administration correlates with airway metabolome alterations and weight loss in obese insulin resistant asthmatics

  (2a) Classification of obesity, waist circumference and waist-to-hip ratio (WHR) will be determined according to the WHO definitions. At baseline and at 12 weeks post-probiotic administration, glucose, Leptin and lipid profile panels will be analyzed from plasma prepared from whole blood collected from fasting individuals. (2b) The recruited subjects will have a HOMA-IR \>5. At baseline and at 12 weeks after probiotics/placebo administration, potential change in insulin sensitivity will be calculated as described in methods above. (2c) Determine if probiotic-mediated changes in leptin, weight gain and insulin sensitivity correlates with airway metabolome alterations compared to placebo controls. Unique airway metabolome signatures comparing probiotics and placebo control groups will be correlated with lowered leptin levels, increased weight loss and increased insulin sensitivity. For the above aims, changes over the 12 weeks will be compared between groups.

  12 weeks

• Determine if microbiome/metabolome changes in probiotics group correlates with changes in asthma biomarkers and improved clinical outcomes compared to placebo in obese insulin resistant asthmatics

  (3a) At baseline and at 12 weeks post-probiotics or placebo administration, asthma biomarkers such as FeNO, IgE, peripheral neutrophils and eosinophils as well as proinflammatory plasma cytokines (IL-6, TNF-α, IL-1β) will be measured. Innate and adaptive immune cells will be enumerated by multiparameter flow cytometry in peripheral blood. These biomarkers will be correlated with changes in microbiome/metabolome identified above in Aim 1 between groups. (3b) At baseline and at 12 weeks post-probiotics or placebo administration, spirometry (FEV1 and FVC), exacerbations/steroid exposure, asthma control test (ACT) and asthma control questionnaire, Asthma Quality of Life Questionnaire (AQLQ) will be performed. Comparison in differences will be made between the groups.

  12 weeks

Study Arms (2)

Probiotic

EXPERIMENTAL

Subjects will receive a probiotic supplement to take by mouth daily.

Dietary Supplement: Probiotic

Placebo

PLACEBO COMPARATOR

Subjects will receive a placebo to take by mouth daily.

Dietary Supplement: Placebo

Interventions

Placebo DIETARY_SUPPLEMENT

10 subjects will receive a placebo daily for 12 weeks.

Placebo

Probiotic DIETARY_SUPPLEMENT

10 subject will receive a probiotic daily for 12 weeks.

Probiotic

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may not qualify if:

• Asthma related hospitalization within 90 days of enrollment
• Asthma exacerbation requiring \>3 days of oral corticosteroids within 28 days of enrollment
• Comorbid lung diseases other than asthma
• Pregnancy or planned pregnancy
• Inability to understand study procedures and/or provide informed consent
• Other significant medical conditions based on discretion of PI

Sponsors & Collaborators

• American Lung Association: collaborator
• University of Alabama at Birmingham: lead

Study Sites (1)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

MeSH Terms

Conditions

Asthma; Obesity; Insulin Resistance

Interventions

Probiotics

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Dietary Supplements; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Jessy Deshane, PhD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: June 29, 2023
• First Posted: July 18, 2023
• Study Start: April 1, 2024
• Primary Completion (Estimated): June 30, 2026
• Study Completion (Estimated): June 30, 2026
• Last Updated: January 16, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)