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

NCT00490100 | Terminated Phase 1 Results DMC

• 2 other identifiers: 07017107-I-0171
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief 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. ...

Conditions

Growth Failure; X-linked Severe Combined Immunodeficiency (XSCID); Growth Hormone Resistence

Keywords

X-Linked Severe Combined Immune Deficiency (XSCID); Growth Hormone; Insulin-Like Growth Factor 1 (IGF)-1; Bone Age; Growth Failure; XSCID; X-Linked Severe Combined Immunodeficiency

Outcome Measures

Primary Outcomes (2)

• Safety of Study Drug

  Rates of adverse events related to study drug

  1 year

• Change in Growth Rate on Study Drug

  Growth rate on intervention is compared with growth rate before intervention for each participant.

  During intervention, up to 2 years

Study Arms (1)

Treatment

EXPERIMENTAL

Treatment

Drug: Increlex

Interventions

Increlex DRUG

Treatment

Eligibility Criteria

• Age: 2 Years - 20 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Buckley RH, Schiff RI, Schiff SE, Markert ML, Williams LW, Harville TO, Roberts JL, Puck JM. Human severe combined immunodeficiency: genetic, phenotypic, and functional diversity in one hundred eight infants. J Pediatr. 1997 Mar;130(3):378-87. doi: 10.1016/s0022-3476(97)70199-9.

  PMID: 9063412 BACKGROUND

• Puck JM, Pepper AE, Henthorn PS, Candotti F, Isakov J, Whitwam T, Conley ME, Fischer RE, Rosenblatt HM, Small TN, Buckley RH. Mutation analysis of IL2RG in human X-linked severe combined immunodeficiency. Blood. 1997 Mar 15;89(6):1968-77.

  PMID: 9058718 BACKGROUND

• Leonard WJ, Shores EW, Love PE. Role of the common cytokine receptor gamma chain in cytokine signaling and lymphoid development. Immunol Rev. 1995 Dec;148:97-114. doi: 10.1111/j.1600-065x.1995.tb00095.x.

  PMID: 8825284 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Failure to Thrive; X-Linked Combined Immunodeficiency Diseases

Interventions

mecasermin

Condition Hierarchy (Ancestors)

Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Severe Combined Immunodeficiency; Primary Immunodeficiency Diseases; Infant, Newborn, Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Limitations and Caveats

Due to limited subject participation, there is insufficient complete data to generate meaningful statistics for the outcome measures. Instead, this data will be reported as a case series.

Results Point of Contact

• Title: De Ravin, SukSee
• Organization: National Institute of Allergy and Infectious Diseases

sderavin@mail.nih.gov

+1 301 496 6772

Study Officials

• Suk S De Ravin, M.D.

  National Institute of Allergy and Infectious Diseases (NIAID)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 21, 2007
• First Posted: June 22, 2007
• Study Start: June 1, 2007
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: July 3, 2015
• Results First Posted: July 3, 2015

Record last verified: 2014-03

Locations

US (1)