Protocol Number: 07-I-0171

Title:

Treatment for Growth Failure in Patients with X-Linked Severe Combined Immunodeficiency (XSCID): A Phase 2 Study Assessing Safety and Clinical Response to Treatment with Insulin-like Growth Factor-1 (IGF-1)

Number:

07-I-0171

Summary:

This study will evaluate the safety and effectiveness of insulin-like growth factor-1 (IGF-1) to treat patients with X-linked severe combined immunodeficiency (XSCID). Those who have XSCID lack white blood cells that protect their bodies from invasion by all types of germs. IGF-1 is the main hormone responsible for the body's growth and metabolism. As a medication, IGF-1 is Increlex[™ (Trademark)] (mecasermin),

Patients ages 2 to 20 who have not yet begun puberty, have a diagnosis of XSCID, and are shorter than the 3rd percentile for their age may be eligible for this study. This study will last about 3 years, and patients' visits will be scheduled at 3-month intervals. Patients will have a physical history and exam, X-rays, electrocardiogram, blood tests, and body measurements.

Patients will take estradiol orally for 2 days, to help avoid false results of growth hormone (GH) levels in blood samples. Then provocation testing is done, with two tests back to back. It determines blood levels of GH and the body's response to testing with drugs called arginine and clonidine. Patients are admitted to the pediatric inpatient unit and will have an intravenous (IV) line placed in the arm. Arginine is given by IV over 30 minutes, and blood samples are taken. Right after arginine testing, the clonidine tablet is given. The IGF-1 generation test is then done to see if the body makes IGF-1 as a product in response to injections of GH for 5 consecutive days. This test does not require that patients are inpatients, but after Day 8, patients must be admitted to the pediatric unit to have blood sampling, start Increlex injections, and start close monitoring of blood sugar levels. They will learn how to do a self-injection and follow other advice. They will complete records about the injection site, symptoms, and side effects-keeping records for at least the first 2 days after going home, with each dose change, and as needed. Patients stick their fingertip and place a small drop of blood on a blood sugar monitoring strip. The strip is put into a glucometer-a small hand-held device to measure the blood sugar level. Patients will be instructed to always have a source of sugar available in case blood sugar is too low.

Sponsoring Institute:

National Institute of Allergy and Infectious Diseases (NIAID)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): None

Eligibility Criteria:

INCLUSION CRITERIA:

Participants Must:

-Have a diagnosis of XSCID

-Have NO fusion of epiphyses/closed growth plates as determined by X-ray of left wrist and hand (special skeletal age film)

-Be between 2 years to 20 years old and have not completed puberty

-Consent to permit blood and/or tissue samples for storage

-Demonstrate short stature: height below the 3 rd percentile for chronological age

-Have a primary care physician at home

-Demonstrate growth failure, defined as growth velocity (measured as linear growth) that is less than 5% to 10% of that expected for children of the same age group, over the past 12 months

-Willingness to remain hospitalized for several days

-Provide evidence of serum IGF-1 level performed within the preceding 6 months and the results fall below normal limits for age

EXCLUSION CRITERIA:

Participants Must NOT:

-Have fusion of epiphyseal plates

-Be under the age of 2 years or have reached completion of puberty

-Have a serum IGF-1 level that is within normal limits for age

-Be above the 3rd percentile height for chronological age

-Demonstrate any history of anaphylactic reaction or hypersensitivity to mecasermin or any component of the drug's formulation

-Have any active or suspected neoplasia

-Demonstrate signs of intracranial hypertension as evidenced by papilledema upon examination by fundoscopy

-Have any condition that, in the investigator's opinion, places the patient at undue risk by participating in the study

-Be unwilling to undergo testing or procedures associated with this protocol

Special Instructions:

Currently Not Provided

Keywords:

X-Linked Severe Combined Immune Deficiency (XSCID)

Growth Hormone

Insulin-Like Growth Factor 1 (IGF)-1

Bone Age

Growth Failure

Recruitment Keyword(s):

XSCID

X-Linked Severe Combined Immunodeficiency

Growth Failure

Condition(s):

Growth Failure

X-linked Severe Combined Immunodeficiency (XSCID)

Growth Hormone Resistence

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Drug: Increlex

Procedure/Surgery: Arginine Provocation Test

Procedure/Surgery: Clonidine Provocation Test

Procedure/Surgery: IGF-1 Generation Test

Drug: IVIG

Procedure/Surgery: Haplo-Identical Bone Marrow Transplant

Supporting Site:

National Institute of Allergy and Infectious Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Buckley RH, Schiff RI, Schiff SE, et al. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997;130:378-387

Puck JM, Pepper AE, Henthorn PS, et al. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood. 1997;89:1968-1977

Leonard WJ, Shores EW, Love PE. Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev. 1995;148:97-114

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Networks and Applications, CC.

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