Gene Transfer Therapy for Severe Combined Immunodeficieny Disease (SCID) Due to Adenosine Deaminase (ADA) Deficiency: A Natural History Study

NCT00001255 | Completed

• 2 other identifiers: 90019590-HG-0195
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This study will monitor the long-term effects of gene therapy in patients with severe combined immunodeficiency disease (SCID) due to a deficiency in an enzyme called adenosine deaminase (ADA). It will also follow the course of disease in children who are not receiving gene therapy, but may have received enzyme replacement therapy with the drug PEG-ADA. ADA is essential for the growth and proper functioning of infection-fighting white blood cells called T and B lymphocytes. Patients who lack this enzyme are, therefore, immune deficient and vulnerable to frequent infections. Injections of PEG-ADA may increase the number of immune cells and reduce infections, but this enzyme replacement therapy is not a definitive cure. In addition, patients may become resistant or allergic to the drug. Gene therapy, in which a normal ADA gene is inserted into the patient's cells, attempts to correcting the underlying cause of disease. Patients with SCID due to ADA deficiency may be eligible for this study. Patients may or may not have received enzyme replacement therapy or gene transfer therapy, or both. Participants will have follow-up visits at the National Institutes of Health in Bethesda, Maryland, at least once a year for a physical examination, blood tests, and possibly the following additional procedures to evaluate immune function:

1. 1.Bone marrow sampling - A small amount of marrow from the hip bone is drawn (aspirated) through a needle. The procedure can be done under local anesthesia or light sedation.
2. 2.Injection of small amounts of fluids into the arm to study if the patient's lymphocytes respond normally.
3. 3.Administration of vaccination shots.
4. 4.Collection of white blood cells through apheresis - Whole blood is collected through a needle placed in an arm vein. The blood circulates through a machine that separates it into its components. The white cells are then removed, and the red cells, platelets and plasma are returned to the body, either through the same needle used to draw the blood or through a second needle placed in the other arm.
5. 5.Blood drawings to obtain and study the patient's lymphocytes.

Conditions

Severe Combined Immunodeficiency

Keywords

Retroviral Vector; Gene Therapy; PEG-ADA; Severe Combined Immunodeficiency (SCID); Adenosine Deaminase Deficiency (ADA)

Interventions

ADA PBSC DRUG

ADA Umbilical Cord Blood Cells DRUG

Transduced Lymphocytes DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

New patients will not be treated under protocol 90-HG-0195 as new and improved vectors and technologies have become available in the recent years. New patients with ADA deficiency, however, may be enrolled in protocol 90-HG-0195 for clinical evaluation of their immune system and pre-treatment testing of transduction procedures.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Human Genome Research Institute (NHGRI): lead

Study Sites (1)

National Human Genome Research Institute (NHGRI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Giblett ER, Anderson JE, Cohen F, Pollara B, Meuwissen HJ. Adenosine-deaminase deficiency in two patients with severely impaired cellular immunity. Lancet. 1972 Nov 18;2(7786):1067-9. doi: 10.1016/s0140-6736(72)92345-8. No abstract available.

  PMID: 4117384 BACKGROUND

• Donofrio J, Coleman MS, Hutton JJ, Daoud A, Lampkin B, Dyminski J. Overproduction of adenine deoxynucleosides and deoxynucletides in adenosine deaminase deficiency with severe combined immunodeficiency disease. J Clin Invest. 1978 Oct;62(4):884-7. doi: 10.1172/JCI109201.

  PMID: 308954 BACKGROUND

• Cohen A, Hirschhorn R, Horowitz SD, Rubinstein A, Polmar SH, Hong R, Martin DW Jr. Deoxyadenosine triphosphate as a potentially toxic metabolite in adenosine deaminase deficiency. Proc Natl Acad Sci U S A. 1978 Jan;75(1):472-6. doi: 10.1073/pnas.75.1.472.

  PMID: 272665 BACKGROUND

MeSH Terms

Conditions

Severe Combined Immunodeficiency; Severe combined immunodeficiency due to adenosine deaminase deficiency

Condition Hierarchy (Ancestors)

Primary Immunodeficiency Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Infant, Newborn, Diseases; DNA Repair-Deficiency Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Study Design

• Study Type: observational
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: September 1, 1990
• Study Completion: July 1, 2002
• Last Updated: March 4, 2008

Record last verified: 2002-07

Locations

US (1)