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

Primary Purpose

Chronic Obstructive Pulmonary Disease

Status

Completed

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Chlorhexidine

Placebo

About this trial

This is an interventional basic science trial for Chronic Obstructive Pulmonary Disease focused on measuring COPD, Bacteria

Eligibility Criteria

40 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

VA Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Chlorhexidine

Placebo

Arm Description

Oral Rinse

Outcomes

Primary Outcome Measures

Change in Sputum Bacteria Biomass

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

Breathlessness, Cough, and Sputum Scale (BCSS)

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)

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.

Full Information

NCT ID

NCT02252588

First Posted

September 25, 2014

Last Updated

December 3, 2020

Sponsor

University of Minnesota

Collaborators

Veterans Medical Research Foundation, Flight Attendant Medical Research Institute

1. Study Identification

Unique Protocol Identification Number

NCT02252588

Brief Title

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

Acronym

CLIMB

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

December 2020

Overall Recruitment Status

Completed

Study Start Date

September 1, 2014 (Actual)

Primary Completion Date

December 15, 2019 (Actual)

Study Completion Date

January 1, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Minnesota

Collaborators

Veterans Medical Research Foundation, Flight Attendant Medical Research Institute

4. Oversight

Data Monitoring Committee

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Chronic Obstructive Pulmonary Disease

Keywords

COPD, Bacteria

7. Study Design

Primary Purpose

Basic Science

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Masking

ParticipantInvestigator

Allocation

Randomized

Enrollment

44 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Chlorhexidine

Arm Type

Experimental

Arm Description

Oral Rinse

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Oral Rinse

Intervention Type

Drug

Intervention Name(s)

Chlorhexidine

Intervention Description

Oral Rinse

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

Oral Rinse

Primary Outcome Measure Information:

Title

Change in Sputum Bacteria Biomass

Description

Time Frame

Baseline, 8 weeks

Secondary Outcome Measure Information:

Title

Breathlessness, Cough, and Sputum Scale (BCSS)

Description

Time Frame

Baseline, 8 weeks

Title

Change in St George Respiratory Quotient (SGRQ)

Description

Time Frame

baseline, 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Chris Wendt, MD

Organizational Affiliation

VA Medical Center

Official's Role

Principal Investigator

Facility Information:

Facility Name

VA Medical Center

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55417

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

34903538

Citation

Pragman AA, Fieberg AM, Reilly CS, Wendt C. Chlorhexidine oral rinses for symptomatic COPD: a randomised, blind, placebo-controlled preliminary study. BMJ Open. 2021 Dec 13;11(12):e050271. doi: 10.1136/bmjopen-2021-050271.

Results Reference

derived

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

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