Growth and Metabolic Response to GH and GnRHa Treatment Versus GH Alone in Boys Born SGA.
Condition: SGA and Growth
Study type: Interventional

Summary: 
      A 2-arms randomized open prospective intervention study to determine the Growth and metabolic
      response to growth hormone and gonadotropin-releasing hormone agonist treatment versus growth
      hormone alone in boys born SGA.

      All subjects will be treated with NorditropinSimplex at a dosage of 100mcg/kg/d.

      At onset of puberty, subjects will be randomized into either combined treatment with GH and
      GnRHa or GH alone.
    

Detailed description: 
      A 2-arms randomized open prospective intervention study including 20 boys, in order to
      determine the effect of growth hormone (GH) and gonadotropin-releasing hormone agonist
      treatment versus growth hormone (GnRHa) alone on growth and metabolic response.

      Objectives:

      The primary objective is to investigate the effect of delaying the pubertal process by
      pubertal suppression on growth and final height of boys who were born SGA and treated with
      GH.

      The secondary objectives are to determine the metabolic effect of the combined therapy of GH
      plus gonadotropin agonists to that of GH alone on the dietary intake, serum leptin, ghrelin,
      IGF-1, lipid and lipoprotein concentrations prior to and during treatment, and to assess the
      quality of life between the two groups.

      Study population:

      20 prepubertal boys.

      Inclusion Criteria:

        1. Ages 10-13

        2. IUGR

        3. Height of at least 2 standard deviations below the mean height for chronological age and
           sex according to the 2000 standards from the Centers for Disease Control and Prevention
           (CDC).

        4. prepubertal(Tanner stage 1) at commencement of trail.

        5. Peak GH above 10ng/ml in at least one provocative test for GH secretion.

        6. Signed informed consent form.

      Exclusion criteria:

        1. Growth retardation associated with malignancy, severe chronic disease, genetic syndromes
           and endocrine disorders.

        2. Diabetes.

        3. Treatment with any medical product which may interfere with GH effects.

      Trail design:

      A prospective, randomized controlled study assessing the impact of two years of combined
      treatment with GH and GnRHa on height of boys with severe growth failure due to SGA with
      height >2.25 SDS , compared with GH alone.

      All subjects will be treated with NorditropinSimplex at a dosage of 100mcg/kg/d. At onset of
      puberty (testicular volume greater than 4 ml in consecutive examinations) subjects will be
      randomized into either combined treatment with GH and GnRHa or GH alone.

      Methods:

        1. Urine test will be held every three months.

        2. X-ray photograph for bone age determination will be taken at baseline and every year
           after.

        3. Blood will be taken at baseline and every year after in order to evaluate the following
           parameters: Lipid and lipoprotein concentrations, ghrelin, leptin, glucose, insulin and
           HbA1c.

        4. Blood will be taken on randomization visit and three months after in order to evaluated
           the following parameters: LH, FSH and Testosterone

        5. Blood will be taken at baseline and every half a year after to evaluate levels of IGF-1.

        6. For evaluation of the growth hormone response, additional blood tests will be preformed
           one month and three months after treatment with growth hormone.

        7. On every blood and urine that will be taken, proteomic analysis will be held.

        8. Before treatment with growth hormone, one year after treatment and in the end of the
           study quality of life questionnaire, appetite questionnaire and Psychological
           questionnaires will be filled.

      The safety of growth hormone treatment will be assessed from:

        1. Monitoring of adverse events.

        2. Measurement of HbA1c.

        3. Measurement of hematology, serum biochemistry and urinalysis laboratory variables.

        4. Measurement of fasting glucose and insulin concentrations.

        5. IGF-1

        6. Physical examinations and measurements of vital signs height and body weight.

        7. Measurement of bone age.
    

Intervention name(s): growth hormone and gonadotropin-releasing hormone agonist; growth hormone
Intervention type(s): Drug; Drug
Intervention description(s): GH & GNRHa treatment; GH treatment
Intervention MeSH terms: Hormones
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: SGA; GH; GnRHa; IGF-1