Clinical trial NCT05949255: Probiotics and Insulin Resistance in Obese Asthmatics
Official title: Probiotics and Insulin Resistance in Obese Asthmatics
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: Asthma
Obesity
Insulin Resistance
Lead sponsor: University of Alabama at Birmingham
Sponsor class: OTHER
Collaborators: name: American Lung Association
First posted: 2023-07-18
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Participants for this study will be recruited through the UAB Asthma Clinic under an IRB approved protocol. The Asthma Clinic at UAB has over 350 unique patients. The composition of the clinic is 73% female, 58% non-hispanic white and 34% black/African American, and 63% have a BMI over 30. Asthma is defined by a constellation of symptoms including episodic dyspnea, cough, wheeze, and chest tightness with evidence of airway hyperresponsiveness. The subjects recruited to this study will be seen in the Asthma Clinic at UAB. All participants will have a clinical history of symptoms consistent with a diagnosis of asthma, and testing supporting the presence of airway hyperresponsiveness as denoted by either a positive bronchodilator response, a positive methacholine challenge test, or a high degree of clinical suspicion for asthma but unable to perform either of those tests. This study will recruit obese asthmatics with an Insulin Resistance score \>5. Classification of obesity, waist circumference and waist-to-hip ratio (WHR) will be determined according to the WHO definitions. Body mass index (BMI kg/m2) of \>30 will be considered obese. The Homeostatic model assessment (HOMA)-IR values \>5 will be classified as those with severe IR. Additional patient information including age, sex, demographics and BMI will be collected at baseline and at 12 weeks. The HOMA-IR estimates steady-state β- cell function and insulin sensitivity and will be calculated by multiplying the fasting plasma glucose (mg/dl) value by serum insulin value (mIU/ml) value divided by 405. Potential participants will be prescreened for inclusion in this study. Patients in the Asthma Clinic who have previously agreed to participate in a local biorepository will have all of the prerequisite biometric data available, so only those individuals meeting inclusion criteria will be contacted for participation.

Participants (n=20 obese asthmatics) will be fasted for at least 12 hours prior to blood sampling at baseline. 20 obese asthmatic patients with BMI \>30 and with IR \>5 will be randomized and 10 patients will receive 1 capsule/day of 500 mg of probiotic supplement (Floragen Digestion, American Lifelines, Baraboo, WI ). This is a probiotic combination product ((Lactobacillus acidophilus, Bifidobacterium lactis, and Bifidobacterium longum (1.5 x 1010 CFUs/capsule)) and 10 patients in placebo group will receive 500 mg of starch per day for 12 weeks. For both study groups, both genders will be recruited equally with an anticipated distribution of approximately 40% African American and 60% Caucasian subjects. At baseline and at end of 12 weeks, respiratory function tests will be carried out and clinical endpoint measurements will be made. Additionally, nasal filters, nasal washes, rectal swabs, peripheral blood mononuclear cells and serum samples will be collected. 40 ml of peripheral blood samples will be collected at baseline and at 12 weeks after administration of probiotics or placebo control. These samples will be used for endpoint measurements in peripheral blood and serum. Microbiome analyses of nasal washes and rectal swabs will be carried out in collaboration with the UAB Microbiome core. For metabolomics studies, sampling of the upper airways of 60 participants with paired nasal filters and washes. The nasal filter method consists of introducing \~ 1/3 to 1/2 of a 15 × 25 mm filter paper made of synthetic absorptive matrix (Leukosorb, Pall Life Sciences) into one of the nostrils and placing it laterally against the anterior portion of the inferior nasal turbinate. The nasal filter will be left in the nostril for a minimum of 30 s and up to 2 min. Once removed, it will be placed into a sterile container. The nasal wash method consisted of using a bulb syringe to flush 3-5 mL of sterile, non-bacteriostatic, normal saline solution into the contralateral nostril. Both nasal filters and washes will be centrifuged and the supernatant transferred to a freezer and stored at - 80 °C until further processing.

Eligibility criteria: InclusionCriteria:

* Age \> 18 years
* All patients will be obese asthmatics. Patients will have a body mass index \>30 and insulin resistance\>5.
* Asthmatics who have stable disease without changes to their asthma related medications for 3 months prior to enrollment

Exclusion Criteria:

* 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

Primary outcomes:
measure: Determine if probiotic administration modulates airway microbiome/metabolome in obese insulin resistant asthmatics
timeFrame: 12 weeks
measure: 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
timeFrame: 12 weeks
measure: 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
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
Study officials:
affiliation: University of Alabama at Birmingham
name: Jessy Deshane, PhD
role: PRINCIPAL_INVESTIGATOR
References: