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Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01929967
Recruitment Status : Completed
First Posted : August 28, 2013
Last Update Posted : June 27, 2014
Litron Laboratories
Information provided by (Responsible Party):
Terence Prendiville, Boston Children's Hospital

Brief Summary:

The investigators aim with this study is to investigate the mechanisms of immune deficiency in patients with heterotaxy syndrome through the use of novel biomarkers and a prospective questionnaire survey documenting the burden of infectious sequelae following enrollment. It is known that patients with under-active spleens (functional asplenia or hyposplenia) secondary to other (non-cardiac) conditions such as Sickle Cell Disease or Inflammatory Bowel Disease have a characteristic paucity of a B cell sub-class known as IgM memory B cell. This specific sub-class of B cell normally matures in the spleen and in those with an improperly functioning spleen a significant deficiency of this B cell class is seen on flow cytometry.

Similarly, these same patients are noted to have increased amounts of 'junk' DNA / nuclear remnant in their red cells. This is seen on microscopy as a dark particle inside the red cell and is termed a Howell Jolly Body (normally less than 2% of red cells have these dark particles present). Part of a functioning spleen's normal task is to rid the blood of red cells that contain nuclear remnants and an under-active spleen gets behind on this task with a build-up of Howell Jolly Bodies in red cells present in the bloodstream. Flow cytometry can very quickly and accurately quantify Howell Jolly Bodies as well as IgM memory B cells from a small (~1.5cc) sample of blood. Normal IgM memory B cell ranges are known for healthy children from infancy onwards allowing interpretation of results against normative data ranges.

The investigators aim to enroll 10 patients in this pilot study who have a diagnosis of heterotaxy syndrome (both asplenia and polysplenia) and to prospectively follow them after obtaining the initial biomarker sample. The family will be contacted once every two weeks for a period of 12 weeks and asked a series of simple questions taking approximately 5 minutes on any recent infectious sequelae or symptoms. The questions will elucidate history of minor illness such as low-grade fever or cough to more significant events such as admission for in-patient antibiotic therapy of bacterial sepsis. Ultimately, with this pilot study, the investigators hope to obtain sufficient data to support funding applications for a larger, multi-center trial that will allow us to develop biomarker thresholds for future risk of sepsis.

Condition or disease
Heterotaxy Syndrome

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Study Type : Observational
Actual Enrollment : 10 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Defining Immunodeficiency in Heterotaxy Syndrome: Pilot Study Data
Study Start Date : August 2013
Actual Primary Completion Date : June 2014
Actual Study Completion Date : June 2014

Heterotaxy syndrome
Patients with a diagnosis of heterotaxy syndrome, as objectively defined by visceral heterotaxy (malrotation, interrupted inferior vena cava) with either documented polysplenia or asplenia by radiological imaging

Primary Outcome Measures :
  1. Howell Jolly Body quantification [ Time Frame: At time of recruitment ]
  2. IgM Memory B Cell quantification [ Time Frame: At time of recruitment ]

Secondary Outcome Measures :
  1. Results of phone questionnaire of parents documenting infectious symptoms and sequelae [ Time Frame: Once every 2 weeks for 12 weeks following enrollment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Patients with a diagnosis of heterotaxy syndrome from inpatient and outpatient Cardiology settings at Boston Children's Hospital

Inclusion Criteria:

  • Diagnosis of heterotaxy syndrome, as objectively defined by visceral heterotaxy (malrotation, interrupted inferior vena cava) with either documented polysplenia or asplenia by radiological imaging.
  • 0-12 years old.

Exclusion Criteria:

  • Other known immunodeficiency or hyposplenic states (22q11, hypogammaglobulinemia, sickle hemoglobinopathy, liver cirrhosis or portal hypertension, organ transplantation, Fanconi syndrome, HIV or AIDS, chronic corticosteroid use, cancer, chemotherapy or other immunomodulating drug exposure, Addison's disease or pan-hypopituitarism, surgical splenectomy).
  • Red blood cell transfusion within the last 90 days as the donated red blood cells may interfere with calculation of the subject's Howell Jolly Body count. Patient enrollment will be deferred until 90 days has elapsed, assuming other eligibility requirements are met.

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 identifier (NCT number): NCT01929967

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United States, Massachusetts
Boston Children's Hospital
Boston, Massachusetts, United States, 02115
Sponsors and Collaborators
Boston Children's Hospital
Litron Laboratories
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Principal Investigator: Terence Prendiville, MB BCh BAO Boston Children's Hospital
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Responsible Party: Terence Prendiville, Pediatric Cardiology Fellow, Boston Children's Hospital Identifier: NCT01929967    
Other Study ID Numbers: IRB-P00007001
First Posted: August 28, 2013    Key Record Dates
Last Update Posted: June 27, 2014
Last Verified: June 2014
Keywords provided by Terence Prendiville, Boston Children's Hospital:
Heterotaxy syndrome
Additional relevant MeSH terms:
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Heterotaxy Syndrome
Pathologic Processes
Heart Defects, Congenital
Cardiovascular Abnormalities
Cardiovascular Diseases
Heart Diseases
Splenic Diseases
Lymphatic Diseases
Abnormalities, Multiple
Congenital Abnormalities