The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive Pulmonary Disease

Phase 2

Completed

Conditions: Chronic Obstructive Pulmonary Disease

Interventions: Drug: Chlorhexidine
Other: Placebo

Registration Number: NCT02252588

Lead Sponsor: University of Minnesota

Brief Summary: Determine the effect of twice-daily chlorhexidine oral rinse on oral and lung microbiota biomass in subjects with chronic obstructive pulmonary disease (COPD) with chronic bronchitis. Our primary outcome will be to compare the microbiota biomass (number of bacteria as measured by 16S rRNA copy number) of induced sputum and the oral cavity before and after 8 weeks of twice-daily chlorhexidine oral rinse (n=25) compared to controls (n=25) using qPCR and next-generation sequencing of the bacterial 16S rRNA gene comparing total bacterial biomass

Detailed Description: Our hypothesis is that 8 weeks of chlorhexidine oral rinse will decrease microbiota biomass compared to baseline and those on placebo. Furthermore, we hypothesize that chlorhexidine treatment will: i) decrease lung and oral microbiota diversity; ii) alter microbiota taxonomic composition in the lung and oral cavity; iii) decrease systemic inflammation as measured by blood high sensitivity C-reactive protein (hsCRP), fibrinogen and leukocyte count; and iv) demonstrate a trend towards improvement in respiratory health status as measured by the Breathlessness, Cough, and Sputum Scale (BCSS)\[1, 2\] and St. George's Respiratory Questionnaire (SGRQ).

Subaim 1: Determine if chlorhexidine alters the lung and oral rinse microbiota diversity and taxonomic composition. Our hypothesis is that chlorhexidine oral rinse will decrease the diversity (Shannon and inverse Simpson diversity indices) and taxonomic composition of both oral and lung microbiota compared to those on placebo as determined by next-generation sequencing of the bacterial 16S rRNA gene.

Subaim 2: Determine the impact of chlorhexidine on systemic inflammation. Our hypothesis is that the decrease in lung microbiota biomass is associated with a decrease in systemic inflammation as measured by blood hsCRP, fibrinogen, and leukocyte count.

Subaim 3: Determine if respiratory symptoms associate with the lung microbiota biomass. Our hypothesis is that chlorhexidine will demonstrate improved respiratory health status as measured by the BCSS and SGRQ.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 44

Inclusion Criteria

Willingness to undergo sputum induction
Capability to provide written informed consent
Age ≥ 40 years and ≤ 85 years
FEV1/FVC ratio (post bronchodilator) ≤70%
FEV1 (post bronchodilator) ≤ 65%
Presence or high likelihood of chronic cough and sputum production defined as one of the following:

Presence of chronic cough and sputum will be defined by responses to the first two questions on the SGRQ. Subjects who respond positively to both question 1 (cough) and question 2 (sputum) on the SGRQ as either "several days per week" or "almost every day" will be eligible.

COPD exacerbation within the previous 12 months defined as taking antibiotics and/or prednisone for respiratory symptoms, hospitalization or emergency department visit for respiratory illness.

Current or former smoker with lifetime cigarette consumption of > 10 pack-years
Negative serum pregnancy test at the baseline visit if patient is a pre-menopausal female (menopause defined as absence of a menstrual cycle in the last 12 months)
Must be fluent in speaking the English language
Have a minimum of four teeth

Exclusion Criteria

Not fully recovered for at least 30 days from a COPD exacerbation.
Treated with antibiotics in the last 2 months.
The presence of dentures (full plate).
Active oral infection being treated by health care professional.
Current use of chlorhexidine or over-the-counter mouth washes in the last 2 months.
Known allergy or sensitivity to chlorhexidine
Unstable cardiac disease
Clinical diagnosis of asthma, bronchiectasis, cystic fibrosis, or severe alpha-1 antitrypsin deficiency
Active lung cancer or history of lung cancer if it has been less than 2 years since lung resection or other treatment. If history of lung cancer, must have no evidence of recurrence in the 2 years preceding the baseline visit.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Chlorhexidine	Placebo	Oral Rinse
Placebo	Placebo	Oral Rinse
Chlorhexidine	Chlorhexidine	Oral Rinse
Placebo	Chlorhexidine	Oral Rinse

Primary Outcome Measures

Name	Time	Method
Change in Sputum Bacteria Biomass	Baseline, 8 weeks	Samples underwent DNA extraction and 16S rRNA quantification and 16S rRNA V4 MiSeq sequencing was performed at the University of Minnesota Genomics Center. The biomass was the number of bacteria as measured by 16S rRNA copy number. To adjust biomass for the size of the sputum sample, raw counts were normalized by dividing by the sample volume or mass.

Secondary Outcome Measures

Name	Time	Method
Breathlessness, Cough, and Sputum Scale (BCSS)	Baseline, 8 weeks	The Breathlessness, Cough, and Sputum Scale (BCSS) is a brief, three-item, patient-reported outcome measure in which each of the three symptoms assessed by the measure is represented by a single item. Patients are asked to evaluate each symptom/item on a 5-point Likert-type scale, ranging from 0 to 4. Total scores range from 0 to 12 with higher scores indicating a more severe manifestation of the symptom.
Change in St George Respiratory Quotient (SGRQ)	baseline, 8 weeks	The St George Respiratory Quotient (SGRQ) contains 50 items measuring symptoms of and activities affected by obstructive airway disease. Total score is a sum of item scores and ranges from 0 to 100, with higher scores indicating more limitations. The minimally significant difference is 4.