Mycobacterium Avium-Intracellulare InfectionPhase 1NCT00111397
Adjuvant Cytokine Therapy to Treat Pulmonary Mycobacterium Avium Complex Infection
A Phase 1 study testing Cytokine therapy and Interferon Gamma, GM-CSF in people with Mycobacterium Avium-Intracellulare Infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 1 site in United States.
Trial summary
Mycobacterium avium complex (MAC) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Mycobacterium Avium-Intracellulare Infection
- What is being tested?
- Cytokine therapy and Interferon Gamma, GM-CSF
- Type of treatment
- Surgery or procedure
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 13 May 2005to 4 Aug 2010
- Phase
- Phase 1
- 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
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- To be eligible for this protocol, a patient must meet the following five criteria:
- Diagnosed with M. avium complex (MAC) lung disease or other pulmonary mycobacterial infection based on the 1997 version of American Thoracic Society (ATS) diagnostic criteria and have positive AFB smear or culture for mycobacterial infection at least three months prior to the date of enrollment. Patients with only histological evidence of mycobacterial infection without positive smear or culture will not qualify for this protocol even if they meet the ATS diagnostic criteria for nontuberculous mycobacterial lung infection.
- A patient must have radiographic evidence on high resolution computerized tomography of changes that are consistent with pulmonary mycobacterial infection. These include, but are not limited to: multiple small nodules (less than 5 mm), and cylindrical bronchiectasis.
- The patient must be on a treatment regimen based on ATS guidelines that has been stable for at least three months. By stable, we mean that the patient has been tolerating the regimen without any significant adverse reactions, and that no new agents have been begun in the last three months.
- The patient must be female and can be post-menopausal (either through natural menopause or surgical removal of her ovaries) or menstruating. If the patient is still menstruating and randomized to a study group receiving a cytokine she must agree to monthly pregnancy testing, while on study, as well as to utilizing a barrier type of contraception or abstinence. She must not be under 40 years of age at the time of enrollment in the study.
- The patient must be enrolled in protocol # 01-I-0202 ("Natural History, Genetics, Phenotype, and Treatment of Non-Tuberculoid Mycobacterial Infections").
Who cannot join
- Patients with pulmonary MAC disease who do not meet the above entry criteria.
- Patients with any of the following preexisting medical conditions:
- HIV positive
- asthma
- active cancer requiring treatment
- hepatic disease (defined as either a history of cirrhosis, or grade 3 or 4 hepatic toxicity by the Toxicity Table in Appendix II of protocol)
Show all 28Show fewer
- Patients who are unable to tolerate bronchoscopy. This will be defined by the following criteria:
- A pulse oximetry reading less than 100% when given supplemental oxygen at 100% FiO2.
- Clinically significant reactive airway disease that does not respond to bronchodilators.
- Patients with the following laboratory abnormalities:
- creatinine greater than 1.5 mg/dL
- Hemoglobin less than 9 mg/dL
- WBC less than 3,000
- Platelets less than 150,000
- ALT greater than 82 U/L, or AST greater than 78 U/L.
- Bilirubin greater than 2.0 mg/dL
- Alkaline phosphates greater than 232 U/L
- Patients with a preexisting allergy or history of allergic reactions to study or protocol medications. These include, but are not necessarily limited to: IFN-gamma, GM-CSF, azithromycin/ clarithromycin, ethambutol, rifampin/ rifabutin, anesthetic agents employed in bronchoscopy, or any yeast-derived products.
- Patients who are unable to maintain the described follow up schedule. Likewise, patients who are unable to give informed consent are excluded from the study.
- Patients with clinical diagnosis of cystic fibrosis.
- Patients who are either currently smoking, or have a previous history of smoking that exceeds 20 pack years.
- Patients with prior treatment with either IFN-gamma or GM-CSF within the last three months.
- Patients with known history of cardiac, endocrine, neurologic or other medical conditions that the principal investigator deems dangerous or unsuitable for enrollment will be excluded.
- Patients who are either pregnant or lactating. Also, menstruating patients who are randomized to a study group receiving a cytokine and refuse to use appropriate barrier forms of contraception or abstinence during this trial be excluded.
- Patients who, at any time during this trial, have an active lung infection caused by either Staphylococcus or a gram negative rod are excluded from this trial until this infection has been successfully treated.
- Patients that need to use supplemental oxygen.
- Patients who have a Forced Vital Capacity less than 40% predicted.
- Patients who are unable to walk and participate in the 6MWT.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: A Study of Adjuvant Cytokine Therapy in Pulmonary Mycobacterium Avium Complex and Other Pulmonary Nontuberculous Mycobacterial Infections
Mycobacterium avium complex (MAC) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. With half or more of all patients failing standard three-drug therapy, this is an insidious disease with a poor prognosis. Under the natural history protocol of nontuberculous mycobacterial infection (NTM; #01-I-0202), 46 patients with diagnosed pulmonary MAC disease are being studied. Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection. Cytokines are particularly important in the activaction of macrophages, which help to clear mycobacterial infection. Interferon gamma 1b (Actimmune) and GM-CSF (Leukine) are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution, respectively. A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection. Given the poor outcomes of therapy and the persistent, debilitating nature of the disease, new therapies are desperately needed, and many are being tried without benefit of scientific foundation. Currently, there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously. This protocol proposes to perform a pilot study to evaluate the effects, if any, of these macrophage stimulating cytokines in the context of ongoing pulmonary MAC infection.
Aims:
Read more
To determine the local and systemic effect, if any, of adjuvant IFN gamma and GM-CSF in pulmonary MAC patients.
Methods:
Fifteen patients will be randomized into three treatment groups of five patients each. The first group will receive a standard drug regimen, based on the 1997 ATS guidelines. The second and third groups, in addition to receiving the standard therapy, will also receive three months of (IFN{gamma}) and GM-CSF, respectively. All patients will undergo bronchoscopy with bronchoalveolar lavage (BAL) at the beginning of the study, after three months, and at six months.
In addition to obtaining traditional subjective and objective clinical measures, both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs. In vitro studies on typ...
Read the detailed description
Mycobacterium avium complex (MAC) and other pulmonary nontuberculous mycobacteria (P-NTM) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. With half or more of all patients failing standard three-drug therapy, this is an insidious disease with a poor prognosis. Under the natural history protocol of nontuberculous mycobacterial infection (NTM; #01-I-0202), 46 patients with diagnosed pulmonary MAC disease, 20 patients with M. abscessus disease, and 14 with other types of mycobacteria (M. fortuitum, M. massiliense, M. mucogenicum and M. chelonae) are being studied.
Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection. Cytokines are particularly important in the activation of macrophages, which help to clear mycobacterial infection. Interferon gamma 1b (Actimmune) and GM-CSF (Leukine) are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution, respectively. A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection. Given the poor outcomes of therapy and the persistent, debilitating nature of the disease, new therapies are desperately needed, and many are being tried without benefit of scientific foundation. Currently, there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously. This protocol proposes to perform a pilot study to evaluate the effects, if any, of these macrophage stimulating cytokines in the context of ongoing pulmonary mycobacterial infection.
Aims:
To determine the local and systemic effect, if any, of adjuvant IFN gamma and GM-CSF in P-NTM patients.
Methods:
Fifteen patients will be randomized into three treatment groups of five patients each. The first group will receive a standard drug regimen, based on the 1997 ATS guidelines. The second and third groups, in addition to receiving the standard therapy, will also receive three months of (IFN{gamma}) and GM-CSF, respectively. All patients will undergo bronchoscopy with bronchoalveolar lavage (BAL) at the beginning of the study, after, after three months, and at six months.
In addition to obtaining traditional subjective and objective clinical measures, both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs, In vitro studies on type II alveolar macrophages culled from these patients before and after cytokine therapy will also be performed.
- Being tested
- Cytokine therapy, Interferon Gamma, GM-CSF
- Keywords
- Mycobacterial, Interferon, GM-CSF, Microarray, Proteomics, Mycobacterium Avium Complex Infection, MAC
- Medical subject headings
- Mycobacterium avium-intracellulare Infection
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cytokine therapyProcedure or surgery
Interferon Gamma, GM-CSFDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 May 2005 (estimated)
- Study start13 May 2005
- Primary completion4 Aug 2010
- Study completion4 Aug 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Mycobacterium Avium-Intracellulare InfectionStudies of the same condition, open and under way.
- More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The 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 1
- Primary purpose
- Treatment
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00111397
- Sponsor's protocol ID
- 050156
- Other IDs
- 05-I-0156
- Status last verified
- 4 Aug 2010
- First submitted
- 19 May 2005
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Prince DS, Peterson DD, Steiner RM, Gottlieb JE, Scott R, Israel HL, Figueroa WG, Fish JE. Infection with Mycobacterium avium complex in patients without predisposing conditions. N Engl J Med. 1989 Sep 28;321(13):863-8. doi: 10.1056/NEJM198909283211304.
PubMed 2770822Iseman MD, Buschman DL, Ackerson LM. Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. Am Rev Respir Dis. 1991 Oct;144(4):914-6. doi: 10.1164/ajrccm/144.4.914.
PubMed 1928970Chalermskulrat W, Gilbey JG, Donohue JF. Nontuberculous mycobacteria in women, young and old. Clin Chest Med. 2002 Sep;23(3):675-86. doi: 10.1016/s0272-5231(02)00010-2.
PubMed 12371003
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Study of Adjuvant Cytokine Therapy in Pulmonary Mycobacterium Avium Complex and Other Pulmonary Nontuberculous Mycobacterial Infections
- ClinicalTrials.gov ID
- NCT00111397
- Acronym / sponsor ID
- 050156
- Keywords
- Mycobacterial, Interferon, GM-CSF, Microarray, Proteomics, Mycobacterium Avium Complex Infection, MAC
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
- Study start
- 13 May 2005
- Primary completion
- 4 Aug 2010 (actual)
- Study completion
- 4 Aug 2010 (actual)
- First posted
- 20 May 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Mycobacterium avium complex (MAC) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. With half or more of all patients failing standard three-drug therapy, this is an insidious disease with a poor prognosis. Under the natural history protocol of nontuberculous mycobacterial infection (NTM; #01-I-0202), 46 patients with diagnosed pulmonary MAC disease are being studied. Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection. Cytokines are particularly important in the activaction of macrophages, which help to clear mycobacterial infection. Interferon gamma 1b (Actimmune) and GM-CSF (Leukine) are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution, respectively. A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection. Given the poor outcomes of therapy and the persistent, debilitating nature of the disease, new therapies are desperately needed, and many are being tried without benefit of scientific foundation. Currently, there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously. This protocol proposes to perform a pilot study to evaluate the effects, if any, of these macrophage stimulating cytokines in the context of ongoing pulmonary MAC infection.
Aims:
To determine the local and systemic effect, if any, of adjuvant IFN gamma and GM-CSF in pulmonary MAC patients.
Methods:
Fifteen patients will be randomized into three treatment groups of five patients each. The first group will receive a standard drug regimen, based on the 1997 ATS guidelines. The second and third groups, in addition to receiving the standard therapy, will also receive three months of (IFN{gamma}) and GM-CSF, respectively. All patients will undergo bronchoscopy with bronchoalveolar lavage (BAL) at the beginning of the study, after three months, and at six months.
In addition to obtaining traditional subjective and objective clinical measures, both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs. In vitro studies on typ...
Detailed description
Mycobacterium avium complex (MAC) and other pulmonary nontuberculous mycobacteria (P-NTM) are ubiquitous organisms that cause isolated pulmonary disease in otherwise healthy patients with yet undefined susceptibilities. Patients typically present with a history of chronic cough, eventually progressing to hemoptysis, fever, and hypoxia. With half or more of all patients failing standard three-drug therapy, this is an insidious disease with a poor prognosis. Under the natural history protocol of nontuberculous mycobacterial infection (NTM; #01-I-0202), 46 patients with diagnosed pulmonary MAC disease, 20 patients with M. abscessus disease, and 14 with other types of mycobacteria (M. fortuitum, M. massiliense, M. mucogenicum and M. chelonae) are being studied.
Numerous studies have suggested that a dysregulation in cytokine production may make these patients susceptible to mycobacterial infection. Cytokines are particularly important in the activation of macrophages, which help to clear mycobacterial infection. Interferon gamma 1b (Actimmune) and GM-CSF (Leukine) are two cytokine therapies that have been approved in the treatment of chronic granulomatous disease and post-transplantation hematopoietic reconstitution, respectively. A number of in vitro studies suggest that either or both of these therapies may help to clear MAC infection. Given the poor outcomes of therapy and the persistent, debilitating nature of the disease, new therapies are desperately needed, and many are being tried without benefit of scientific foundation. Currently, there are no prospective trials that show any effect of these drugs in the lung delivered subcutaneously. This protocol proposes to perform a pilot study to evaluate the effects, if any, of these macrophage stimulating cytokines in the context of ongoing pulmonary mycobacterial infection.
Aims:
To determine the local and systemic effect, if any, of adjuvant IFN gamma and GM-CSF in P-NTM patients.
Methods:
Fifteen patients will be randomized into three treatment groups of five patients each. The first group will receive a standard drug regimen, based on the 1997 ATS guidelines. The second and third groups, in addition to receiving the standard therapy, will also receive three months of (IFN{gamma}) and GM-CSF, respectively. All patients will undergo bronchoscopy with bronchoalveolar lavage (BAL) at the beginning of the study, after, after three months, and at six months.
In addition to obtaining traditional subjective and objective clinical measures, both proteomic and genomic analysis of the BAL will be performed to determine if cytokine therapy effects any detectable change in the lungs, In vitro studies on type II alveolar macrophages culled from these patients before and after cytokine therapy will also be performed.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Diagnosed with M. avium complex (MAC) lung disease or other pulmonary mycobacterial infection based on the 1997 version of American Thoracic Society (ATS) diagnostic criteria and have positive AFB smear or culture for mycobacterial infection at least three months prior to the date of enrollment. Patients with only histological evidence of mycobacterial infection without positive smear or culture will not qualify for this protocol even if they meet the ATS diagnostic criteria for nontuberculous mycobacterial lung infection.
- A patient must have radiographic evidence on high resolution computerized tomography of changes that are consistent with pulmonary mycobacterial infection. These include, but are not limited to: multiple small nodules (less than 5 mm), and cylindrical bronchiectasis.
- The patient must be on a treatment regimen based on ATS guidelines that has been stable for at least three months. By stable, we mean that the patient has been tolerating the regimen without any significant adverse reactions, and that no new agents have been begun in the last three months.
- The patient must be female and can be post-menopausal (either through natural menopause or surgical removal of her ovaries) or menstruating. If the patient is still menstruating and randomized to a study group receiving a cytokine she must agree to monthly pregnancy testing, while on study, as well as to utilizing a barrier type of contraception or abstinence. She must not be under 40 years of age at the time of enrollment in the study.
- The patient must be enrolled in protocol # 01-I-0202 ("Natural History, Genetics, Phenotype, and Treatment of Non-Tuberculoid Mycobacterial Infections").
Key exclusion criteria (28 listed)
- Patients with pulmonary MAC disease who do not meet the above entry criteria.
- HIV positive
- asthma
- active cancer requiring treatment
- hepatic disease (defined as either a history of cirrhosis, or grade 3 or 4 hepatic toxicity by the Toxicity Table in Appendix II of protocol)
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 |
|---|---|---|
| Cytokine therapy | Procedure or surgery | – |
| Interferon Gamma, GM-CSF | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 2770822Prince DS, Peterson DD, Steiner RM, Gottlieb JE, Scott R, Israel HL, Figueroa WG, Fish JE. Infection with Mycobacterium avium complex in patients without predisposing conditions. N Engl J Med. 1989 Sep 28;321(13):863-8. doi: 10.1056/NEJM198909283211304.
- Background: PubMed 1928970Iseman MD, Buschman DL, Ackerson LM. Pectus excavatum and scoliosis. Thoracic anomalies associated with pulmonary disease caused by Mycobacterium avium complex. Am Rev Respir Dis. 1991 Oct;144(4):914-6. doi: 10.1164/ajrccm/144.4.914.
- Background: PubMed 12371003Chalermskulrat W, Gilbey JG, Donohue JF. Nontuberculous mycobacteria in women, young and old. Clin Chest Med. 2002 Sep;23(3):675-86. doi: 10.1016/s0272-5231(02)00010-2.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Cytokine therapy and Interferon Gamma, GM-CSF in people with Mycobacterium Avium-Intracellulare 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 6 inclusion and 28 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 2 Jul 2017. 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 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.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00111397, 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 2 Jul 2017.