A Study to Optimize Growth Hormone Dosing in Children With Chronic Kidney Disease by Measuring IGF-1 Levels in Blood
Condition: Kidney Failure, Chronic; Growth Hormone Deficiency
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Failure, Chronic
Intervention: Nutropin AQ
Intervention description: Nutropin AQ
Intervention MeSH terms: Hormones
Phase: Phase 4
Study type: Interventional
Primary purpose: Diagnostic
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: None (Open Label)
Enrollment: 17.0
Sex: All
Minimum age: 2 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Short stature; children; kidney failure, chronic; Growth

Summary:

      Treatment with growth hormone (GH; a hormone made by the body that stimulates growth) has
      been shown to be helpful in treating children with chronic kidney disease who fail to grow.
      The amount of growth that is seen in children treated with growth hormone varies widely for
      unknown reasons. Growth hormone works by producing another hormone in the liver called
      insulin-like growth factor-1, or IGF-1 for short. IGF-1 stimulates the bones to grow. The
      amount of IGF-1 in the blood may directly affect the amount of growth in each child. At this
      time, growth hormone therapy in children depends on giving a certain dose of growth hormone
      for each child based on his or her weight. If after 3-6 months on this dose of growth hormone
      the change in height is not enough, then the dose of growth hormone is increased until enough
      growth is seen. This method of dosing of growth hormone may take a long time and is
      complicated and time-consuming.

      The purpose of this study is to measure the amount of IGF-1 produced by the body as a result
      of giving 2 different doses of growth hormone in children for 7 days only. The study
      investigator hopes to find the most favorable level of IGF-1 generated after 7 days of growth
      hormone that correlates with good growth of children with kidney disease. Then instead of
      dosing growth hormone by weight, like is done now, researchers can dose growth hormone by the
      amount of IGF-1 that the body produces. Being able to dose more effectively will save
      valuable time for the child to grow and will shorten the overall duration of growth hormone
      therapy.

      The investigators will also determine the effect of inflammatory cytokines Il-6 and TNF-alpha
      on growth hormone insensitivity and hence IGF-1 generation test in the same population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Males and females between 2-18 years of age with chronic renal failure.

          -  Estimated creatinine clearance between 25-75 ml/min/1.73 m2 calculated by the Schwartz
             formula.

          -  Height standard deviation score (SDS) more than -1.88 or annual height velocity SD of
             more than -2.0 for age and sex for the preceding 6 months.

          -  No history of growth hormone therapy.

          -  Cystinosis subjects may qualify for the study if they meet other inclusion criteria
             and have an estimated creatinine clearance of 25-75 ml/min/1.73 m2.

          -  Bone age less than 16 years for boys and less than 13 years for girls.

          -  Subjects with chronic kidney failure who are off steroid therapy or other drugs that
             interfere with growth for at least 6 months.

        Exclusion Criteria:

          -  Subjects on dialysis and kidney transplant recipients.

          -  Patients with significant renal osteodystrophy or an intact parathyroid (PTH) level
             more than 500 pg/ml over the last 3 months prior to enrollment.

          -  Diabetes mellitus.

          -  History of malignancy.