Three Times Weekly (TIW) Growth Hormone Therapy in Children on Hemodialysis

This study has been completed.
Sponsor:
Collaborator:
Genentech
Information provided by (Responsible Party):
John Mahan, Nationwide Children's Hospital
ClinicalTrials.gov Identifier:
NCT00943995
First received: July 21, 2009
Last updated: August 6, 2013
Last verified: August 2013
  Purpose

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.


Condition Intervention Phase
Kidney Failure, Chronic
Renal Dialysis
Drug: somatropin
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: TIW Growth Hormone Therapy in Children on Hemodialysis

Resource links provided by NLM:


Further study details as provided by Nationwide Children's Hospital:

Primary Outcome Measures:
  • Primary Endpoints: Changes in Height SDS and Height velocity SDS [ Time Frame: Will be monitored every 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Changes in Weight SDS, lean body mass, normalized protein catabolic rate and quality of life. [ Time Frame: Will be monitored every 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: July 2010
Study Completion Date: August 2012
Primary Completion Date: August 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: somatropin
    0.35 mg/Kg/week divided into 3 doses, each dose being given at the end of the dialysis treatment.
    Other Name: Nutropin AQ
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).
  Eligibility

Ages Eligible for Study:   1 Month to 16 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic Renal Failure on Hemodialysis
  • Tanner 1
  • Bone Age <12
  • Below the 3rd %tile for height or have growth velocity < 3rd %tile and are not on SQ rGH Rx
  • At baseline, study population will also have to have documentation of normal thyroid status, secondary hyperparathyroidism will be controlled in acceptable range (iPTH < 800), adequate dialysis (Kt/V >1.2) and normal acid-base status.
  • expected to be on hemodialysis at least 6 months

Exclusion Criteria:

  • Anyone not meeting the inclusion criteria.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00943995

Locations
United States, Georgia
Children's Healthcare of Atlanta at Egleston
Atlanta, Georgia, United States, 30322
United States, Missouri
Children's Mercy Hospital
Kansas City, Missouri, United States, 64108
United States, New York
Montefiore Medical Center
Bronx, New York, United States, 10467
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
Children's Memorial Hermann Hospital-TMC
Houston, Texas, United States, 77030
Sponsors and Collaborators
Nationwide Children's Hospital
Genentech
Investigators
Principal Investigator: John D Mahan, MD Nationwide Children's Hospital
  More Information

Publications:

Responsible Party: John Mahan, Principal Investigator, Nationwide Children's Hospital
ClinicalTrials.gov Identifier: NCT00943995     History of Changes
Other Study ID Numbers: 907-M02R
Study First Received: July 21, 2009
Last Updated: August 6, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Nationwide Children's Hospital:
End Stage Kidney Disease
Kidney Failure
Short stature
Growth Hormone therapy

Additional relevant MeSH terms:
Kidney Failure, Chronic
Renal Insufficiency
Renal Insufficiency, Chronic
Kidney Diseases
Urologic Diseases
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 31, 2014