sPLA2 in EBC During Acute Chest Syndrome

• ClinicalTrials.gov Identifier: NCT03250585
• Recruitment Status: Completed
• First Posted: August 15, 2017
• Last Update Posted: September 26, 2018
• Sponsor: Virginia Commonwealth University
• Information provided by (Responsible Party): Virginia Commonwealth University

Tracking Information

• First Submitted Date: August 10, 2017
• First Posted Date: August 15, 2017
• Last Update Posted Date: September 26, 2018
• Actual Study Start Date: January 19, 2018
• Actual Primary Completion Date: June 14, 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 6, 2017)

• sPLA2 Measurement in EBC during ACS [ Time Frame: Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission) ]
  sPLA2 level in EBC at Time point 1 (during acute ACS episode) as measured by ELISA
• sPLA2 Levels in EBC during ACS versus Steady-State [ Time Frame: Time point 1 to Time point 2 (at 2 week follow-up) ]
  Comparison of sPLA2 levels in EBC from Time point 1 (during acute illness) and Time Point 2 (return to baseline status at 2 week follow up).

Original Primary Outcome Measures (submitted: August 10, 2017)

• sPLAS Level [ Time Frame: Time point 1 (within 48 hours of admission) ]
  Comparison of sPLAS between EBC and plasma samples as measured by...
• sPLAS Level [ Time Frame: Time point 2 (within 48 hours of admission) ]
• sPLAS Level [ Time Frame: Time point 3 (within 48 hours of admission) ]

Current Secondary Outcome Measures (submitted: October 6, 2017)

sPLA2 levels in EBC versus Plasma [ Time Frame: Time point 1 (within either 48 hours of admission or time of diagnosis of ACS, if not present on admission)] ]

Difference in sPLA2 levels from EBC compared with Plasma during Time point 1 (during acute illness)

• Original Secondary Outcome Measures (submitted: August 10, 2017): sPLAS level [ Time Frame: 2 week follow up ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: sPLA2 in EBC During Acute Chest Syndrome
• Official Title: Secretory Phospholipases A2 in Exhaled Breath Condensate From Sickle Cell Patients With Acute Chest Syndrome: A Feasibility Study
• Brief Summary: Secretory phosholipases A2 (sPLA2) are significantly elevated in the plasma of sickle cell disease patients with acute chest syndrome (ACS), and similar enzymes have been measured in exhaled breath condensate (EBC), which is collected easily and non-invasively. The investigators hypothesize that sPLA2 will be measurable in EBC samples from sickle cell patients with acute chest syndrome.

Detailed Description

The purpose of this research study is to test the ease and effectiveness of collecting exhaled breath condensate (liquid) to measure levels of a biomarker, secretory phospholipases A2 (sPLA2) in people with sickle cell disease during an attack of acute chest syndrome. sPLA2 levels have been reported to be much higher in persons with acute chest syndrome and might be useful to diagnose and to evaluate the effects of therapy.

Serial monitoring of plasma sPLA2 levels might lead to earlier or more accurate detection of acute chest syndrome and monitoring of its progression or improvement in patients with sickle cell disease. However, there is a significant inherent risk of frequent blood collection further dropping the blood (hemoglobin) levels of an already anemic patient. If sPLA2 can be measured in exhaled breath condensate, this non-invasive and well-tolerated sample collection might allow for serial monitoring of the enzyme without depleting the patient's already diminished blood supply.

• Study Type: Observational
• Study Design: Observational Model: Case-Only; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided
• Biospecimen: Not Provided
• Sampling Method: Non-Probability Sample
• Study Population: Sickle cell patients with acute chest syndrome

Condition

• Sickle Cell Disease
• Acute Chest Syndrome

Intervention

• Diagnostic Test: Exhaled Breath Condensate (EBC)
  Serial EBC samples will be collected within 48 hours of acute chest syndrome (ACS) diagnosis and at 2 week follow up
• Diagnostic Test: Plasma Sample
  Serial plasma samples will be collected within 48 hours of acute chest syndrome (ACS) diagnosis and at 2 week follow up

Study Groups/Cohorts

Sickle Cell Patients with Acute Chest Syndrome

Sickle cell patients with active acute chest syndrome (ACS) from which samples of EBC and plasma will be collected during acute illness within 48 hours of admission with or diagnosis of ACS (Time point 1) in 3 sessions each 1 hour apart (Time point 1a, 1b, and 1c), and 2 weeks after discharge when have returned to steady-state (Time point 2). Time point 2 samples will serve as control (baseline) samples.

Interventions:

• Diagnostic Test: Exhaled Breath Condensate (EBC)
• Diagnostic Test: Plasma Sample

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: August 10, 2017): 6
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: June 14, 2018
• Actual Primary Completion Date: June 14, 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Diagnosis of sickle cell anemia (the most severe types of sickle cell disease) as demonstrated by one of the following genotypes: HbSS, HbSβ0
2. Age ≥ 7 and < 40 years
3. Diagnosis of ACS as defined below
4. EBC collection able to be initiated within 48 hours of diagnosis of ACS

Definition of acute chest syndrome to be used: New radiographic pulmonary infiltrate of at least one complete lung segment in addition to 2 or more of the following symptoms: fever, chest pain, dyspnea, tachypnea, hypoxia. Given the small number of subjects in this feasibility study, we are using the more conservative definition in order to ensure samples are from patients with true ACS. This will increase the likelihood that sPLA2 levels will be high enough for measurement.

Exclusion Criteria:

1. Blood product transfusion in the previous 3 months (due to potential alterations in biomarkers, including sPLA2)
2. Chronic inflammatory conditions other than sickle cell (due to elevation from baseline of sPLA2 in inflammatory conditions)
3. Physical inability to correctly breathe into the mouthpiece for the required amount of time without compromising respiratory status
4. Intubated patients (though EBC can be measured in intubated patients, we will not include this subpopulation for the purpose of this study)
5. Pregnancy (due to the hematologic and respiratory changes that physiologically occur during gestation)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years to 30 Years (Child, Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT03250585
• Other Study ID Numbers: HM20010698
• Has Data Monitoring Committee: Not Provided

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Virginia Commonwealth University
• Original Responsible Party: Same as current
• Current Study Sponsor: Virginia Commonwealth University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Davis D Michael, PhD; Virginia Commonwealth University

• PRS Account: Virginia Commonwealth University
• Verification Date: September 2018