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Nontuberculous Mycobacterial InfectionPhase 1/2NCT01853540

Sildenafil for PNTM Infection

A Phase 1/2 study testing Sildenafil in people with Nontuberculous Mycobacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

Background: Pulmonary nontuberculous mycobacterial (PNTM) infection is caused by a common type of bacteria in the environment. Although PNTM infection is most common in people with lung diseases, it can also affect healthy people. It can be difficult to treat, and affects parts of the body other than the lungs. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Nontuberculous Mycobacterial Infection
What is being tested?
Sildenafil
How many people
10 participants
Where
1 siteUnited States
Study dates
Jan 2013to Oct 2014
Phase
Phase 1/2
Are there results?
None posted in the registry

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 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Adults (18 years of age or older) with PNTM who are currently enrolled on the 01-I-0202 protocol Natural History, Genetics, Phenotype and Treatment of Mycobacterial Infections will be eligible for participation.
  • Subjects must have CBF in the range observed in subjects with PNTM (CBF 8.1 plus or minus 1.4 Hz or lower).
  • Women of childbearing potential must have a negative pregnancy test result.
  • Women of childbearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.

Who cannot join

  • Any subject who, in the opinion of the investigator, is unable or unwilling to comply with the study procedures, medication schedule, or study visits.
  • Use of nitrate medicines, other PDE inhibitors, or other drugs known to have unsafe interactions with sildenafil.
  • Known allergy to sildenafil.
  • History of the following:
  • Recurrent epistaxis.
  • Diabetes or impaired glucose intolerance (risk of retinal hemorrhage with sildenafil is highest in diabetics).
Show all 15Show fewer
  • Portal hypertension.
  • Active pulmonary veno-occlusive disease (PVOD).
  • Use of daytime oxygen supplementation.
  • Unstable or uncontrolled hypertension.
  • Active retinopathy, history of retinal detachment, or hemorrhage.
  • Initiation of agents known to be potent CYP3A4 inhibitors or inducers (e.g., itraconazole, ritonavir, ketoconazole).
  • Any subject who, in the opinion of the investigator, may be at a greater risk of cardiovascular disease or congestive heart failure.
  • Breastfeeding.
  • Co-Enrollment Guidelines: Subjects will be co-enrolled in the 01-I-0202 protocol. They may also be enrolled in 07-I-0142 entitled Research Respiratory Tract Procedures .Co-enrollment in other trials is restricted, other than enrollment in observational studies or those evaluating the use of a licensed medication. Study staff should be notified of co-enrollment as it may require the approval of the principal investigator.

Trial locations and contacts

1 site in 1 country.

United States1 site

  • National Institutes of Health Clinical Center, 9000 Rockville Pike

    Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Sildenafil in Patients With Pulmonary Nontuberculous Mycobacterial Infection

Background:

  • Pulmonary nontuberculous mycobacterial (PNTM) infection is caused by a common type of bacteria in the environment. Although PNTM infection is most common in people with lung diseases, it can also affect healthy people. It can be difficult to treat, and affects parts of the body other than the lungs. For example, PNTM may affect the cilia, the hair-like structures inside the nose and lungs that help move dirt and debris out of the body.
  • Ciliary beat frequency (CBF) is a measurement of how fast cilia move. People with PNTM infection have a lower CBF than healthy people. Nitric oxide (NO) is a gas in the body that may affect CBF. People with PNTM infection produce lower amounts of NO in their noses than healthy people. Researchers want to see if a drug called sildenafil can increase NO production and CBF. If sildenafil can improve these measurements, it may be a useful treatment for PNTM infection.
Read more

Objectives:

  • To study the effect of sildenafil on CBF and NO levels in people with PNTM infection.

Eligibility:

  • Individuals at least 18 years of age who have PNTM infection.
  • Participants must be enrolled in a related National Institutes of Health study on bacterial infections. The study is Natural History, Genetics, Phenotype and Treatment of Mycobacterial Infections.

Design:

  • Participants will be screened with a physical exam and medical history. They will also have heart and lung function tests, as well as tests of NO production in the nose. They will provide samples of sputum and cells from inside the nose.
  • Before the first study visit, participants will collect sputum samples for 24 hours. They will bring the samples to the study visit.
  • At the first study visit, participants will have heart and lung function tests, as well as tests of NO production in the nose. They will provide blood, urine, sputum, and nasal cell samples. They will also receive sildenafil tablets to take at home.
  • Participants will take sildenafil tablets three times a day.
  • The second study visit will be 7 days after the first one. The tests from the first visit will be repeated. Participants will receive more sildenafil tablets to take on the same schedule as before.
  • The third and final study visit will be 30 days after the first one. The tests from the first visit will be repeated. Participants will stop taking sildenafil at this visit.
  • A follow-up phone call will be made about 2 weeks after the final study visit. This call will ask questions about quality of life and any symptoms or side effects of the study.
Read the detailed description

Pulmonary nontuberculous mycobacterial (PNTM) infection has increased over the past several decades, especially in older women. No consistent immunological abnormalities have been found despite extensive investigation. In cystic fibrosis and primary ciliary dyskinesia, mucociliary dysfunction predisposes individuals to high rates of PNTM disease that increases markedly with age.

We studied the respiratory biology of subjects with PNTM and healthy controls and found decreased levels of nasal nitric oxide (nNO) in vivo. Ex vivo analysis of ciliated respiratory epithelium from subjects with PNTM demonstrated an abnormally low resting ciliary beat frequency (CBF) and an abnormal response to toll-like receptor ([TLR]2,TLR3, TLR5, TLR7/8, and TLR9) agonists, compared with respiratory samples from healthy controls. The low CBF response was normalized ex vivo by augmenting the nitricoxide-cyclic guanosine monophosphate pathway; this supplementation had no appreciable effect on the differences in TLR responses observed in subjects with PNTM and healthy controls. The reduced CBF and nNO levels in these subjects reveal possible mechanisms of susceptibility to respiratory infections, as well as possible avenues of directed investigation and therapy.

This is an open-label, interventional study evaluating the effects of sildenafil on CBF in subjects with PNTM infection. The study will also measure the effects of sildenafil on nNO, and it will evaluate the quality of life, exertional capacity, pulmonary function, lower airway microbiology, inflammatory markers, and the safety and tolerability of sildenafil treatment in this population.

The first 5 subjects will receive an oral bolus of sildenafil (40 mg) on day 0 followed by an oral dose of 20 mg 3 times a day (tid) starting on day 1 for approximately 6 days until the study visit on day 7. The remaining 5 subjects will receive an oral dose of sildenafil (20 mg) tid on day 0 for approximately 1 week until the study visit on day 7. Subsequently, the dose will be increased for all subjects to 40 mg tid and will be administered for another 3 weeks until the study visit on day 30 (4 weeks in total). Administering an initial oral bolus will help us examine sildenafil s immediate effects on CBF and safety parameters. The dosing necessary to modulate CBF in this subject population is not yet known, thus, we feel that undertaking a dose-ranging study will allow a thorough evaluation of sildenafil s effects on CBF.

Being tested
Sildenafil
Keywords
Ciliary Beat Frequency (CBF), Nasal Nitric Oxide (nNO), Mucociliary Dysfunction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SildenafilDrug

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Modulation of CBF with sildenafil in subjects with PNTM infection. The study will also measure the effects of sildenafil on nNO, and it will evaluate the quality of life, exertional capacity, pulmonary function, lower airway microbiology, inflam...

    Measured: 30 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted15 May 2013 (estimated)
  2. Study startJan 2013
  3. Primary completionOct 2014
  4. Study completionOct 2014

Resources

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 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
10 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01853540
Sponsor's protocol ID
130075
Other IDs
13-I-0075
Status last verified
Sep 2015
First submitted
10 May 2013
Last updated
25 Sep 2015
Results posted
No

Publications

  • Taiwo B, Glassroth J. Nontuberculous mycobacterial lung diseases. Infect Dis Clin North Am. 2010 Sep;24(3):769-89. doi: 10.1016/j.idc.2010.04.008.

    PubMed 20674803

  • Tortoli E. Clinical manifestations of nontuberculous mycobacteria infections. Clin Microbiol Infect. 2009 Oct;15(10):906-10. doi: 10.1111/j.1469-0691.2009.03014.x.

    PubMed 19845702

  • Karakousis PC, Moore RD, Chaisson RE. Mycobacterium avium complex in patients with HIV infection in the era of highly active antiretroviral therapy. Lancet Infect Dis. 2004 Sep;4(9):557-65. doi: 10.1016/S1473-3099(04)01130-2.

    PubMed 15336223

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Sildenafil in people with Nontuberculous Mycobacterial Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) 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 4 inclusion and 15 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 25 Sep 2015. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Modulation of CBF with sildenafil in subjects with PNTM infection. The study will also measure the effects of sildenafil on nNO, and it will evaluate the quality of life, exertional capacity, pulmonary function, lower airway microbiology, inflam... (time frame: 30 days). 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 NCT01853540, which also lists 3 linked publications.

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 25 Sep 2015.

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