The Longitudinal Evaluation of Autoimmune Pulmonary Alveolar Proteinosis (LongPAP)

June 21, 2021 updated by: Children's Hospital Medical Center, Cincinnati
The major goal of this study is to conduct a prospective, longitudinal study of autoimmune PAP to examine outcome measures for disease severity of potential use in clinical practice and/or clinical research studies. These results will impact the field by: 1) improving an understanding of the clinical course of autoimmune PAP, 2) providing information on various clinical outcome and quality of life outcome measures to guide patients and physicians in making treatment choices, and 3) facilitate the development of pharmaco-therapeutics for autoimmune PAP and 4) better informing PAP researchers.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Detailed Description

PAP is a rare syndrome of surfactant accumulation and resulting hypoxemic respiratory failure that occurs in a number of diseases classified pathogenically into three groups: primary PAP (caused by disruption of GM-CSF signaling - autoimmune PAP, hereditary PAP), secondary PAP (caused by reduction in alveolar macrophage numbers and/or functions), and surfactant dysfunction-related PAP (caused by mutations in genes required for normal surfactant production). In current clinical practice, PAP is diagnosed based on a lung biopsy; an approach that is not able to identify the PAP-causing disease in anyone. Current therapy involves the physical removal of surfactant by a procedure in which the lungs are repeatedly filled with saline and emptied - whole lung lavage, which is invasive, inefficient, and not widely available, especially for children. Importantly, research advances have elucidated the pathogenesis of diseases causing PAP in most patients and have identified new diagnostic and therapeutic approaches. Simple blood-based research tests can now identify the PAP-causing disease in about 95% of patients. Further, several promising potential disease-specific therapies are currently in development. The long-term goals of the Rare Lung Diseases Consortium include improving the diagnosis and therapy of people with PAP. A major goal of this protocol is to conduct a prospective, longitudinal study of autoimmune PAP to examine outcome measures for disease severity for potential use in clinical practice and/or clinical research studies. The investigator's central hypothesis is that a prospective, longitudinal study of autoimmune PAP patients will facilitate the identification of useful outcome measures for use in clinical practice and/or clinical research studies. The specific objectives of the study are to: 1) evaluate blood-based biomarkers of PAP lung disease over time in autoimmune PAP patients, 2) evaluate the natural history/clinical course of autoimmune PAP over time, 3) evaluate quality of life measures over time in autoimmune PAP patients, 4) evaluate physiologic measures of disease over time in autoimmune PAP patients, and 5) evaluate radiologic measures of lung disease progression over time in autoimmune PAP patients. The study design will be observational and will involve recruitment, screening, and enrollment of eligible participants and annual collection of clinical data. The experimental approach will be to assess the rate of change in GM-CSF signaling assay parameters from baseline to 24 months. GM-CSF signaling assay parameters include GM-CSF autoantibody (GMAb) level, pSTAT5-Max, STAT5-phosphorylation index (STAT5-PI), GM-CSF signaling index (GM-SI), and GM-CSF EC50. The study will also assess the progression of autoimmune PAP, including but not limited to use of treatment options, the number and types of infections and other inter-current medical issues with quality of life measures, exercise tolerance, and radiologic imaging. Experimental outcomes will evaluate SP-D, cholestenoic acid, and lipid levels. Anticipated results will establish a natural history/clinical course of autoimmune PAP to better serve patients and providers, to better inform PAP researchers, and validate outcome measures and biomarkers for use in future clinical studies of PAP. These results will impact the field by: 1) improving an understanding of the clinical course of autoimmune PAP, 2) providing information on various clinical outcome and quality of life outcome measures to guide patients and physicians in making treatment choices, and 3) facilitate the development of pharmacotherapeutics for autoimmune PAP and 4) better informing PAP researchers.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
29

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Cincinnati, Ohio, United States, 45229
        • Cincinnati Children's Hospital Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • ADULT
  • OLDER_ADULT
  • CHILD

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

Patients with Pulmonary Alveolar Proteinosis

Description

Inclusion Criteria:

  • Written informed consent must be provided by:

    • Participant if at least 18 years old -OR-
    • Parent/legal guardian if participant is less than 18 years old -AND-
    • Participant provides assent when appropriate

  • History of diagnosis of autoimmune as indicated by a:

    • History of chest CT or x-ray findings compatible with PAP -AND-
    • History of a Positive (Abnormal) serum GMAb test

Exclusion Criteria:

  • Individuals who have a serious medical illness that, in the opinion of the investigator, is likely to interfere with completion of the study will be excluded.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Longitudinal evaluation of GM-CSF autoantibody levels
Time Frame: Baseline, 1 year, and 2 years
Change in GM-CSF autoantibody levels in autoimmune PAP patients over time
Baseline, 1 year, and 2 years
Longitudinal evaluation of the maximal phospho-STAT5 level after GM-CSF stimulation
Time Frame: Baseline, 1 year, and 2 years
Change in phospho-STAT5 levels in autoimmune PAP patients over time
Baseline, 1 year, and 2 years
Longitudinal evaluation of the STAT5 Phosphorylation Index
Time Frame: Baseline, 1 year, and 2 years
Change in the STAT5 phosphorylation index in autoimmune PAP patients over time
Baseline, 1 year, and 2 years
Longitudinal evaluation of the GM-CSF Signaling Index
Time Frame: Baseline, 1 year, and 2 years
Change in GM-CSF signaling index in autoimmune PAP patients over time
Baseline, 1 year, and 2 years
Longitudinal evaluation of the dose GM-CSF to stimulation 1/2 maximal STAT5 phosphorylation (EC50)
Time Frame: Baseline, 1 year, and 2 years
Change in GM-CSF EC50 level in autoimmune PAP patients over time
Baseline, 1 year, and 2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Frequency of therapeutic intervention
Time Frame: Baseline, 1 year, and 2 years
Change over time in the patient's history of a need for therapeutic intervention
Baseline, 1 year, and 2 years
Concurrent infections
Time Frame: Baseline, 1 year, and 2 years
Change over time in the patient's history of concurrent infections
Baseline, 1 year, and 2 years
Blood SP-D
Time Frame: Baseline, 1 year, and 2 years
Change over time in serum SP-D levels
Baseline, 1 year, and 2 years
Blood cholestenoic acid
Time Frame: Baseline, 1 year, and 2 years
Change over time in cholestenoic acid levels
Baseline, 1 year, and 2 years
Blood lipid levels
Time Frame: Baseline, 1 year, and 2 years
Change over time in blood lipid levels
Baseline, 1 year, and 2 years
Quality of Life measured by St. George Respiratory Questionnaire
Time Frame: Baseline, 1 year, and 2 years
Change over time in the overall health, daily life, and perceived well-being in patients with obstructive airways disease. The questionnaire is divided into two parts: Part 1: Symptoms component (frequency & severity) with a 1, 3 or 12-month recall (best performance with 3- and 12-month recall); Part 2: Activities that cause or are limited by breathlessness; Impact components (social functioning, psychological disturbances resulting from airways disease) refer to current state as the recall.
Baseline, 1 year, and 2 years
Shortness of breath measured by San Diego Dyspnea Score
Time Frame: Baseline, 1 year, and 2 years
Change over time in the severity of shortness of breath on a 6-point scale (0 = Not at all, 5 = Maximally or unable to do because of breathlessness) during 21 activities of daily living associated with varying levels of exertion. Three additional questions ask about fear of harm from overexertion, limitations, and fear caused by shortness of breath, for a total of 24 items. If patients do not routinely perform an activity, they are asked to estimate their anticipated shortness of breath. A total sum score ranges from 0 to 120.
Baseline, 1 year, and 2 years
Minimum SpO2 during a standardized exercise protocol
Time Frame: Baseline, 1 year, and 2 years
Change over time in the minimum SpO2 during exercise on a scale of 0 to 100. The study will be stopped if the Sp02 reaches 88%.
Baseline, 1 year, and 2 years
Time during standardized exercise protocol required for SpO2 to fall below 88%
Time Frame: Baseline, 1 year, and 2 years
Change over time in the time for the SpO2 to fall below 88% during the standardized exercise protocol while patients step onto and off of a step for 5 minutes.
Baseline, 1 year, and 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital Medical Center, Cincinnati

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Heart, Lung, and Blood Institute (NHLBI)
Rare Diseases Clinical Research Network

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Bruce Trapnell, MD, Children's Hospital Medical Center, Cincinnati

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 19, 2018

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
September 16, 2020

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
September 16, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
May 7, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 18, 2018

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 22, 2018

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 24, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 21, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2017-7514
  • U54HL127672 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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