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

2014-08-27 03:37:53 | BioPortfolio


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.



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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Growth Failure


Increlex, Arginine Provocation Test, Clonidine Provocation Test, IGF-1 Generation Test, IVIG, Haplo-Identical Bone Marrow Transplant


National Institutes of Health Clinical Center, 9000 Rockville Pike
United States




National Institutes of Health Clinical Center (CC)

Results (where available)

View Results


Published on BioPortfolio: 2014-08-27T03:37:53-0400

Clinical Trials [2385 Associated Clinical Trials listed on BioPortfolio]

ATP and Capsaicin Cough Provocation Test in Chronic Cough and Bronchiectasis

This is a randomized, cross-over, single-blind trial. Eligible patients will be randomly assigned to undergo either capsaicin or adenosine triphosphate (ATP) cough provocation test, follow...

Titrated Quantitative Conjunctival Provocation Test (tqCPT)

The clinical relevance of an allergen-specific sensitization is proven e.g., by allergen challenge tests in clinical routine. Several protocols for different challenge tests such as nasal ...

Measurement of Exhaled Nitric Oxide (NO) and Bronchial Provocation Test With Mannitol as a Predictor of Response to Inhaled Corticosteroids in Chronic Cough

Chronic cough is defined by its persistence beyond 8 weeks. Many conditions can explain the existence of a bronchial inflammation. In the management of chronic cough, the search for bronch...

Nasal Provocation Test With Lysine-Acetylsalicylate (ASA) in Patients With Nonsteroidal Anti-Inflammatory Drugs (NSAIDs) Hypersensitivity

This study aims to compare the efficacy of nasal provocation test with Lysine-Acetylsalicylate in patients with history of NSAIDs hypersensitivity between mucocutaneous symptoms and respir...

Measuring Automated Behavioral Observations & Vocal Expressions (ABOVE)

The investigators propose to synchronize automated measurements of behavior - head, body, and face dynamics, gaze, and vocal prosody - with simultaneous recordings of brain activity in cli...

PubMed Articles [12438 Associated PubMed Articles listed on BioPortfolio]

Reliability of a New Symptom Score in a Titrated Quantitative Conjunctival Provocation Test Supported by an Objective Photodocumentation.

Allergen provocation tests are useful methods for proving the clinical relevance of an allergen-specific sensitization. Among these methods, the conjunctival provocation test (CPT) represents an easy-...

Conjunctival provocation tests: prediction of seasonal allergy.

The conjunctival provocation test (CPT) is often used to clearly identify the specific allergen causing the symptoms of allergic rhinoconjunctivitis but also to assess the clinical efficacy of an alle...

Combined simultaneous arginine clonidine stimulation test: Timing of peak growth hormone (GH) concentration and correlation with clinical indices of GH status.

The aims of this study were to determine if it is possible to truncate a combined simultaneous arginine clonidine stimulation test, and to correlate the outcome of the test with clinical indices of GH...

Is quantitative sIgE serology suitable to distinguish between silent sensitization and allergic rhinitis to D. pteronyssinus?

Recently, an increasing number of studies focus on the debate whether provocation tests might be replaceable by specific IgE serology in patients sensitized to airborne allergens. Objective: Our study...

Which Provocation Test Will Be Added to Routine High-resolution Manometry Protocol in Unexplained Dysphagia?

Medical and Biotech [MESH] Definitions

Application of allergens to the nasal mucosa. Interpretation includes observation of nasal symptoms, rhinoscopy, and rhinomanometry. Nasal provocation tests are used in the diagnosis of nasal hypersensitivity, including RHINITIS, ALLERGIC, SEASONAL.

Diagnostic measurement of the nose and its cavity through acoustic reflections. Used to measure nasal anatomical landmarks, nasal septal deviation, and nasal airway changes in response to allergen provocation tests (NASAL PROVOCATION TESTS).

Fluid obtained by irrigation or washout of the nasal cavity and NASAL MUCOSA. The resulting fluid is used in cytologic and immunologic assays of the nasal mucosa such as with the NASAL PROVOCATION TEST in the diagnosis of nasal hypersensitivity.

A projective test used to evaluate a broad range of personality variables including pathology of thought and perception. The subject's responses to inkblot prints are scored along with subjective interpretation by the test administrator.

A test to determine the lowest sound intensity level at which fifty percent or more of the spondaic test words (words of two syllables having equal stress) are repeated correctly.

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

Quick Search


Relevant Topics

Blood is a specialized bodily fluid that delivers necessary substances to the body's cells (in animals) – such as nutrients and oxygen – and transports waste products away from those same cells.  In vertebrates, it is composed of blo...

Endocrine Disorders
Endocrine disorders are grouped into two categories: hormone imbalance - when a gland produces too much or too little of an endocrine hormone development of lesions (such as nodules or tumors) in the endocrine system, which may or may not affect...

Searches Linking to this Trial