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Interferon Gamma to Treat Leukocyte Adhesion Deficiency Type I

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.
 
ClinicalTrials.gov Identifier: NCT00001905
Recruitment Status : Completed
First Posted : November 4, 1999
Last Update Posted : March 4, 2008
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE November 3, 1999
First Posted Date  ICMJE November 4, 1999
Last Update Posted Date March 4, 2008
Study Start Date  ICMJE April 1999
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Interferon Gamma to Treat Leukocyte Adhesion Deficiency Type I
Official Title  ICMJE Interferon Gamma Administration in Leukocyte Adhesion Deficiency Type I
Brief Summary

This study will evaluate the safety and effectiveness of the drug, interferon gamma, in treating leukocyte adhesion deficiency type I (LAD I). Patients with this inherited immune disorder do not have enough proteins called adhesion molecules on their infection-fighting white blood cells, impairing the ability of these cells to get to the site of infection. As a result, patients have recurrent infections of soft tissues, such as the skin, gums and gastrointestinal tract, and poor wound healing. Infants with severe LAD I often die from multiple infections. Interferon gamma may increase the number of adhesion molecules on white blood cells, and thus improve their function.

Patients with LAD I who weigh more than 13 kilograms (28.5 pounds) may be eligible for this study. Candidates will have personal and family medical histories taken, a physical examination, blood and urine tests and a chest X-ray or computed tomography (CT) scan.

Participants will receive injections of interferon gamma under the skin 3 times a week for 3 months. Adult patients will be taught how to give their own injections (similar to insulin injections for diabetes) and parents will be taught how to administer the shots to their child. Blood samples, usually be between 30 to 90 milliliters (2 to 6 tablespoons), will be drawn just before starting medication and again 1 day, 1 week, 1 month, 3 months and 4 months after therapy begins. At these same time intervals, patients will provide a salt-water mouth rinse specimen, which will be tested for changes in the number of white blood cells during interferon gamma treatment.

Patients will be admitted to the NIH Clinical Center for inpatient evaluations at the start of therapy and again after 1 week, 1month, 3 months and 4 months. The initial screening visit will take a few days and subsequent visits will take 1 to 2 days.

Detailed Description Leukocyte adhesion deficiency type I (LAD I) is a primary immunodeficiency disease resulting from mutations in the gene encoding CD18. Markedly reduced or absent expression of the leukocyte integrin component CD18 causes significant impairment in leukocyte mobilization to inflammatory sites. Clinically, patients have marked leukocytosis and recurrent infections involving soft tissues such as skin, the gastrointestinal tract and gingiva. Death due to infections in early infancy is common with the severe form of LAD I (CD18 expression less than 0.5%), but patients with the moderate phenotype (CD18 expression 1-10%) may survive into young adulthood. To date, therapy consists of antibiotic treatment for infections and bone marrow transplantation when possible. LAD I is also a candidate for future gene therapy. Recently, it has been shown that in vivo administration of interferon gamma (IFN-gamma) upregulates CD18 expression in normals and alters leukocyte trafficking. We hypothesize that modest increases in CD18 expression in LAD I patients with the moderate phenotype or alterations in CD18 independent trafficking could result in detectable clinical changes and possible clinical improvement.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE Leukocyte Adhesion Deficiency Syndrome
Intervention  ICMJE Drug: Interferon gamma
Study Arms  ICMJE Not Provided
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: June¬†23,¬†2005)
5
Original Enrollment  ICMJE Same as current
Study Completion Date  ICMJE March 2002
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

PARTICIPANT INCLUSION CRITERIA:

Leukocyte Adhesion Deficiency type I, as determined by flow cytometry showing less than 10% CD18 expression in association with typical signs of LAD I .

Weight adequate to permit the blood drawing requirements of the protocol, greater than 13 kg.

Patients should be without serious, ongoing, uncontrolled infections.

Adequate hematopoietic, renal and hepatic function, defined as:

Absolute neutrophil count greater than or equal to 1500/microL;

Hemoglobin greater than or equal to 7g/dL (post transfusion or erythropoeitin);

Platelet count greater than or equal to 100,000/microL;

Creatinine less than or equal to 1.5 x upper limit of normal;

Bilirubin less than or equal to 1.5 x upper limit of normal;

AST/SGOT less than or equal to 2.5 x upper limit of normal;

ALT/SGPT less than or equal to 2.5 x upper limit of normal;

Calculated Creatinine Clearance greater than or equal to 60 mL/min.

Karnofsky Performance Status Index greater than or equal to 70.

Written signed informed consent.

PARTICIPANT EXCLUSION CRITERIA:

HIV infection.

Active malignancy.

Symptomatic cardiac disease or ongoing treatment for same.

Pregnant or lactating women.

Surgery during the two weeks prior to the start of IFN-gamma dosing.

Concurrent use of systemic corticosteroids, except for physiologic replacement.

Exposure to any investigational drug within four weeks prior to the start of dosing.

Any other major illness which, in the investigator's judgement, may substantially increase the risk associated with the patients participation in this study.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001905
Other Study ID Numbers  ICMJE 990089
99-I-0089
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 2002

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP