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Inhalation of Granulocyte-macrophage Colony-stimulating Factor (GM-CSF) for Autoimmune Pulmonary Alveolar Proteinosis (PAP)

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ClinicalTrials.gov Identifier: NCT02243228
Recruitment Status : Unknown
Verified September 2014 by Kaifeng Xu, Peking Union Medical College Hospital.
Recruitment status was:  Recruiting
First Posted : September 17, 2014
Last Update Posted : September 17, 2014
Sponsor:
Collaborator:
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Information provided by (Responsible Party):
Kaifeng Xu, Peking Union Medical College Hospital

Brief Summary:
The purpose of the study is to evaluate if inhaled granulocyte-macrophage colony stimulating factor delay the increase in alveolar-arterial oxygen difference, compared to no treatment, for adult patients with mild-to-moderate autoimmune pulmonary alveolar proteinosis in China over a two-year period.

Condition or disease Intervention/treatment Phase
Autoimmune Pulmonary Alveolar Proteinosis Drug: GM-CSF Phase 2

Detailed Description:

Autoimmune pulmonary alveolar proteinosis (PAP, previously known as idiopathic PAP) is a rare interstitial lung disease elicited by the formation of autoantibodies which neutralize the activity of granulocyte-macrophage colony-stimulating factor (GM-CSF) which decreases macrophage clearance of surfactant.

Currently, the standard treatment strategy for PAP is whole lung lavage (WLL),which is invasive and has limitations. Inhaled GM-CSF therapy became a new option for PAP patients not only because of its effectiveness and safety, but it is convenient way for patients who are reluctant to do operation as well. We are planning to prospectively evaluate if inhaled granulocyte-macrophage colony stimulating factor would delay the increase in alveolar-arterial oxygen difference (A-aDO2, which is the most sensitive factor in evaluating APAP5), compared to placebo, for patients with mild-to-moderate autoimmune pulmonary alveolar over a two-year period.

A total of 42 subjects with APAP who meet the inclusion criteria will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower Hospital. After observe APAP patients for 3 months to rule out patients who resolved spontaneously, the participants will undergo randomization (by random number table)and stratified into two different groups by their DSS. Then they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week or no treatment for 6 months, and will be followed on an outpatient basis at 2 weeks, and 1, 3, 6, 9, 12, 15, 18, 21 and 24 months after initiation of therapy.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 42 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Prospective Study of Inhaling Granulocyte-macrophage Colony Stimulating Factor in Adult Patients With Mild-to-moderate Autoimmune Pulmonary Alveolar Proteinosis in China: a Randomized Open-label Study
Study Start Date : August 2014
Estimated Primary Completion Date : August 2017
Estimated Study Completion Date : August 2017

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: GM-CSF, nebulizer
After the patients were randomly divided into two groups, they will be treated by GM-CSF (using nebulizer, 150ug bid) every other week for 6 months.
Drug: GM-CSF
Other Name: HUABEI JIMUXIN




Primary Outcome Measures :
  1. A-aDO2 difference [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Time to relapse [ Time Frame: up to 2 years ]
    The definition of relapse were as follow: 1) newly requirement for whole lung lavage (WLL); or 2) PAP associated death; or 3) a reduction in PaO2 of more than 10mmHg, or an increase in DA-aO2 of more than 10mmHg; or 4) a worsen chest HRCT.

  2. FEV1 difference [ Time Frame: 2 years ]
  3. 6 minutes walking distance difference [ Time Frame: 2 years ]
  4. Severe adverse event [ Time Frame: 2 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Accessible population:

Adult patients with mild-to-moderate autoimmune pulmonary alveolar and without spontaneous remission will be enrolled at Peking Union Medical College Hospital and Nanjing Drum Tower Hospital.

Inclusion Criteria:

  • Adult autoimmune PAP subjects will be included: 1) a positive PAS stain from BALF or lung biopsy; 2) high level of serum anti-GM-CSF antibody (>2.39ug/ml, the cut-off point in our hospital); 3) age above 18 years old; 4) exclude hereditary and secondary PAP.
  • Able to give written informed consent and comply with the requirements of the study.
  • Patients are not eligible for the whole lung lavage (WLL), decided by clinicians.
  • Eligibility for GM-CSF inhalation: 1) Disease severity score (DSS) is 1-3; 2) No treatment with GM-CSF therapy or WLLin the 3 months prior to enrollment. Definition of DSS2: 1, no symptom and PaO2>=70mmHg;2, PaO2>=70mmHg with symptoms;3, PaO2>=60 and <70mmHg; 4, PaO2>=50 and <60mmHg; 5, PaO2<50mmHg.

Exclusion Criteria:

  • Patients will be observed for 3 months and all APAP patients who resolved spontaneously will be excluded from our study.
  • PAP resulting from another condition (e.g. occupational exposure to silica, underlying HIV, respiratory infections, myeloproliferative disorder or leukaemia);
  • A normal or low-titre serum anti-GM-CSF antibody (≤2.39ug/ml);
  • History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies;
  • Chronic lung disease associated with already existing respiratory failure (such as pulmonary emphysema or fibrosis);
  • Other serious medical conditions which, in the opinion of the investigator, would make the patient unsuitable for the study.
  • Pregnancy.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02243228


Contacts
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Contact: Kai-Feng Xu, M.D. 10-69155039 ext 86 kaifeng.xu@gmail.com
Contact: Xin-Lun Tian, M.D. 10-69155039 ext 86 xinlun_t@sina.com

Locations
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China, Beijing
Peking Union Medical College Hospital Recruiting
Beijing, Beijing, China, 100730
Contact: Kai-Feng Xu, M.D.    10-69155039 ext 86    kaifeng.xu@gmail.com   
Contact: Xin-Lun Tian, M.D.    10-69155039 ext 86    xinlun_t@sina.com   
Principal Investigator: Xin-Lun Tian, M.D.         
Sponsors and Collaborators
Peking Union Medical College Hospital
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Investigators
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Principal Investigator: Kai-Feng Xu, M.D. Peking Union Medical College Hosptial
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kaifeng Xu, MD, Peking Union Medical College Hospital
ClinicalTrials.gov Identifier: NCT02243228    
Other Study ID Numbers: XT 01
First Posted: September 17, 2014    Key Record Dates
Last Update Posted: September 17, 2014
Last Verified: September 2014
Keywords provided by Kaifeng Xu, Peking Union Medical College Hospital:
granulocyte-macrophage colony stimulating factor(GM-CSF)
Autoimmune pulmonary alveolar proteinosis (PAP)
Additional relevant MeSH terms:
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Pulmonary Alveolar Proteinosis
Autoimmune Diseases
Lung Diseases
Respiratory Tract Diseases
Immune System Diseases