Treatment for Growth Failure in Patients With X-Linked Severe Combined Immunodeficiency: Phase 2 Study of Insulin-Like Growth Factor-1

• Status: Terminated
• Trial end date: 2012-12-01
• Target enrollment: 0
• Participant gender: All

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.

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• Phase: Phase 1/Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Treatments: Insulin; Mecasermin; Mitogens

Criteria

• INCLUSION CRITERIA:

Participants Must:

• Have a diagnosis of XSCID

• 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

• 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