Chronic Obstructive Pulmonary DiseasePhase 2CLIMBNCT02252588
The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive Pulmonary Disease
A Phase 2 study testing Chlorhexidine in people with Chronic Obstructive Pulmonary Disease, run by University of Minnesota at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 to 85 years
- Conditions the study is for
- Chronic Obstructive Pulmonary Disease
- What is being tested?
- Chlorhexidine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 44 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Sep 2014to 1 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive
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
Read the 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.
- Conditions
- Chronic Obstructive Pulmonary Disease
- Being tested
- Chlorhexidine, Placebo
- Keywords
- COPD, Bacteria
- Medical subject headings
- Pulmonary Disease, Chronic Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ChlorhexidineDrug
Oral Rinse
PlaceboOther
Oral Rinse
| Study group | Role | What they receive |
|---|---|---|
| Chlorhexidine | Experimental | Oral Rinse Receives: Drug: Chlorhexidine; Other: Placebo |
| Placebo | Placebo comparator | Oral Rinse Receives: Drug: Chlorhexidine; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline, 8 weeks
Secondary outcomes (2)
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.
Measured: Baseline, 8 weeks
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.
Measured: baseline, 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Sep 2014 (estimated)
- Study start1 Sep 2014
- Primary completion15 Dec 2019
- Study completion1 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Chronic Obstructive Pulmonary DiseaseStudies of the same condition, open and under way.
- More trials run by University of MinnesotaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 44 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Minnesota
- Sponsor type
- University, hospital or other
- Collaborators
- Veterans Medical Research Foundation, Flight Attendant Medical Research Institute
- Responsible party
- Sponsor
- Investigators
- Chris Wendt, MD, Principal investigator, VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02252588
- Sponsor's protocol ID
- 4526
- Acronym
- CLIMB
- Status last verified
- Dec 2020
- First submitted
- 25 Sep 2014
- Last updated
- 29 Dec 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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.
PubMed 34903538
Study at a glance
From the registry record, last updated by the sponsor on 29 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Chlorhexidine on the Oral and Lung Microbiota in Chronic Obstructive
- ClinicalTrials.gov ID
- NCT02252588
- Acronym / sponsor ID
- CLIMB / 4526
- Conditions
- Chronic Obstructive Pulmonary Disease
- Keywords
- COPD, Bacteria
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 44 participants (actual)
- Lead sponsor
- University of MinnesotaUniversity, hospital or other
- Collaborators
- Veterans Medical Research Foundation, Flight Attendant Medical Research Institute
- Study start
- 1 Sep 2014 (actual)
- Primary completion
- 15 Dec 2019 (actual)
- Study completion
- 1 Jan 2020 (actual)
- First posted
- 30 Sep 2014 (estimated)
- Results
- Posted 29 Dec 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chlorhexidine | Experimental | Drug: Chlorhexidine, Other: PlaceboOral Rinse |
| Placebo | Placebo comparator | Drug: Chlorhexidine, Other: PlaceboOral Rinse |
Who may qualify
- Ages
- 40 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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%
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ChlorhexidineOral Rinse | Drug | Chlorhexidine, Placebo |
| PlaceboOral Rinse | Other | Chlorhexidine, Placebo |
Primary outcome
Change in Sputum Bacteria Biomass
Time frame: 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.
2 secondary outcomes
Breathlessness, Cough, and Sputum Scale (BCSS)
Time frame: Baseline, 8 weeks
Change in St George Respiratory Quotient (SGRQ)
Time frame: baseline, 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Dec 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 34903538Pragman 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Chris Wendt, MD principal investigator
VA Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Chlorhexidine in people with Chronic Obstructive Pulmonary Disease, run by University of Minnesota at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 29 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Dec 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Sputum Bacteria Biomass (time frame: Baseline, 8 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02252588, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2020.