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

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. Identifier: NCT00490100
Recruitment Status : Terminated (Insufficient patient participation)
First Posted : June 22, 2007
Results First Posted : July 3, 2015
Last Update Posted : July 3, 2015
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

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.


Condition or disease Intervention/treatment Phase
Growth Failure X-linked Severe Combined Immunodeficiency (XSCID) Growth Hormone Resistence Drug: Increlex Phase 1 Phase 2

Detailed Description:

This is a Phase 2 protocol evaluating the safety and efficacy of standard dose insulin-like growth factor-1 (IGF-1) for the treatment of growth failure in patients diagnosed with X-linked severe combined immunodeficiency (XSCID). This condition is a fatal inherited immunodeficiency caused by defects in the common cytokine receptor gamma chain (gc), a subunit shared by many cytokine receptors. The common gamma subunit signals through the Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway, a complex intracellular signaling pathway used by many cytokines and growth factors, including growth hormone (GH). Studies have suggested that the gc defect may result in hyporesponsiveness to GH. This is supported by a report of GH hyporesponsiveness in an XSCID child that was successfully ameliorated following immune reconstitution using bone marrow transplantation (BMT). Haplo-identical BMTs for XSCID children often achieve only partial immune reconstitution, and many BMT recipients experience ongoing problems with growth failure, achieving heights well below 2 standard deviations for their chronological age. It is possible that in these partially corrected conditions, administration of IGF-1, a substance the body produces downstream in response to GH, may achieve an improved growth response.

This study proposes to evaluate the safety and efficacy of Increlex(Trademark) (recombinant human IGF-1) for the treatment of patients with XSCID who have growth failure (children with heights less than 3rd percentile for age). Increlex(Trademark) is a Food and Drug Administration-approved drug for treatment of growth hormone non-responsiveness in the general population of children with growth hormone hyporesponsiveness or primary IGF-1 deficiencies. The scientific objectives are to determine safety and to assess the efficacy of using subcutaneous IGF-1 in XSCID patients with growth failure. The long-term goal of this study is to establish improved treatment regimens for growth failure in children with XSCID.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 6 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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)
Study Start Date : June 2007
Actual Primary Completion Date : December 2012
Actual Study Completion Date : December 2012

Arm Intervention/treatment
Experimental: Treatment
Drug: Increlex

Primary Outcome Measures :
  1. Safety of Study Drug [ Time Frame: 1 year ]
    Rates of adverse events related to study drug

  2. Change in Growth Rate on Study Drug [ Time Frame: During intervention, up to 2 years ]
    Growth rate on intervention is compared with growth rate before intervention for each participant.

Information from the National Library of Medicine

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Ages Eligible for Study:   2 Years to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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


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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00490100

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United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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Principal Investigator: Suk S De Ravin, M.D. National Institute of Allergy and Infectious Diseases (NIAID)

Additional Information:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID) Identifier: NCT00490100    
Other Study ID Numbers: 070171
First Posted: June 22, 2007    Key Record Dates
Results First Posted: July 3, 2015
Last Update Posted: July 3, 2015
Last Verified: March 2014
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
X-Linked Severe Combined Immune Deficiency (XSCID)
Growth Hormone
Insulin-Like Growth Factor 1 (IGF)-1
Bone Age
Growth Failure
X-Linked Severe Combined Immunodeficiency
Additional relevant MeSH terms:
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Severe Combined Immunodeficiency
X-Linked Combined Immunodeficiency Diseases
Immunologic Deficiency Syndromes
Failure to Thrive
Immune System Diseases
Infant, Newborn, Diseases
DNA Repair-Deficiency Disorders
Metabolic Diseases
Signs and Symptoms
Genetic Diseases, X-Linked
Genetic Diseases, Inborn
Hypoglycemic Agents
Physiological Effects of Drugs
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Growth Substances