Three Times Weekly (TIW) Growth Hormone Therapy in Children on Hemodialysis
Condition: Kidney Failure, Chronic; Renal Dialysis
MeSH terms: Renal Insufficiency; Kidney Failure, Chronic
Study type: Interventional
Phase: Phase 3

Summary: 
      Hypotheses:

        1. The provision of thrice weekly subcutaneous (SQ) recombinant growth hormone (rGH)
           therapy to children receiving in-center hemodialysis (HD) will result in improved
           growth.

        2. The provision of thrice weekly SQ rGH therapy to children receiving in-center HD will
           result in improved lean body mass, nutritional status and quality of life.

      TIW rGH treatment regimen (0.35 mg/kg/week divided into 3 doses, each dose being given at the
      conclusion of the dialysis treatment) for up to 2 years; growth response, Dual energy X-ray
      absorptiometry (DEXA), and quality of life (QOL) will be measured. The goal is to enroll 20
      children who are Tanner 1 with decreased height SDS and/or decreased height velocity standard
      deviation scoreS (SDS).

      If this therapy is demonstrated to be efficacious and improves growth and QOL, this therapy
      could be easily implemented for all eligible children on HD, since parental acceptance should
      be better without having to administer the rGH at home and compliance for the child will be
      assured.

      The investigators thus propose an important study that has the ability to advance their
      understanding and provide evidence for the best methods to promote growth in children on
      dialysis. The results of this study will result in important information that will be of
      value to the entire pediatric nephrologist community, including health care professionals,
      patients, and families. In a real sense, this study will build on the 2006 Consensus
      Conference guidelines for evaluation and treatment of growth failure in children with chronic
      kidney disease (CKD). This will provide evidence for critical management decisions that can
      help insure better growth opportunities to more children with CKD.
    

Detailed description: 
      Objectives/Aims:

        1. To demonstrate the beneficial effects of thrice weekly SQ rGH Rx on growth in children
           on HD

        2. To demonstrate the beneficial effects of thrice weekly SQ rGH Rx in terms of improved
           lean body mass, nutritional status and quality of life in children on HD

      Study Design:

        1. Study group - Provision of standard weekly dose of SQ rGH (0.35 mg/kg/week divided into
           3 doses, each dose being given at the conclusion of dialysis therapy) for up to 2 years
           to growth retarded (Height SDS < -1.88 or Height velocity < -1.88 SD) children receiving
           HD who are naïve to rGH or who have not been on rGH for at least 12 months. Inclusion
           criteria are: medically cleared for SQ rGH Rx (14); growth potential based on Tanner
           stage 1 with open epiphyses on Bone Age radiographs (Bone age < 12 years); expected to
           require HD for at least 6 more months; at least 6 months of standardized historical
           pre-study anthropometric data (including stadiometer height). Exclusion criteria include
           all medical factors that indicate that rGH therapy should not be used (14), e.g., poor
           nutritional status, poorly controlled acidosis, poor dialysis adequacy (defined by Kt/V
           < 1.2), poorly controlled renal osteodystrophy (PTH > 800). Once the complicating factor
           is addressed and corrected, the child may be considered for the study.

        2. SQ rGH to be provided in-center at the conclusion of dialysis session three times weekly
           for up to 24 months. SQ rGH dose to be adjusted based on dry (euvolemic) weight every
           month during the intervention.

        3. Baseline and monitoring data obtained on each patient on SQ rGH Rx. This will include
           stadiometer measured height for at least 6 months prior to initiation of SQ rGH Rx to
           provide important baseline height and growth velocity to be used to determine magnitude
           of the response.

        4. For children with suboptimal response after 6 months of standard SQ rGH Rx dose
           (annualized growth rate < 2 cm more than the preceding year), the rGH dose will be
           increased to 0.70 mg/kg/week divided into 3 doses (similar to the reported "pubertal"
           dosing regimen used in some GH deficient children).

      Baseline data: Height (stadiometer), Weight, BMI, Height SDS, Height velocity SDS (historical
      past 6 months), Weight SDS, BMI SDS, Hb, BUN, nPCR, serum albumin, serum calcium, serum
      phosphorus, iPTH, electrolytes, high sensitivity CRP (as a marker of inflammation), dialysis
      adequacy (defined by single and double pool Kt/V - Kt/V is a unitless number used to quantify
      hemodialysis and peritoneal dialysis treatment adequacy: K - dialyzer clearance of urea, t -
      dialysis time, V - patient's total body water; in HD the target is 1.2), IGF-1, IGFBP-3, hip
      films and bone age (4,5,6,9). In addition, lean body mass/and fat mass will be assessed by
      DEXA (to standardize the determination of LBM, DEXA to be done mid week, after the dialysis
      treatment, to avoid the excess fluid commonly present after 2 days off dialysis each weekend)
      and quality of life will be assessed by the PedsQL 4.0 Generic Core Scales (10). The
      nutritional parameters that will be determined (wt/ht, ht SDS, BMI, nPCR and serum albumin)
      represent the currently used assessments of nutrition for these patients and have been
      validated as best measures of nutrition in children on dialysis (12).

      Assessments to be repeated at the following intervals:

        1. Height (stadiometer), Weight, Hgb, BUN, nPCR, serum albumin, serum calcium, phosphorus,
           and electrolytes, Kt/V - monthly

        2. CRP, iPTH, IGF-1, IGFBP-3 - every 3 months

        3. PedsQL - every 6 months

        4. DEXA and Bone Age - yearly (and within 1 week of renal transplant if this occurs anytime
           6 months after start of study) - DEXA and Bone Age results will be sent to Nationwide
           Children's and analyzed by our collaborating pediatric radiologist (Larry Binkovitz,
           MD).
    

Intervention name(s): somatropin
Intervention type(s): Drug
Intervention description(s): 0.35 mg/Kg/week divided into 3 doses, each dose being given at the end of the dialysis treatment.
Other intervention name(s): Nutropin AQ
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: End Stage Kidney Disease; Kidney Failure; Short stature; Growth Hormone therapy