Clinical trial NCT00511329: Growth Hormone in Children With Juvenile Rheumatoid Arthritis (JRA) and With Crohn's Disease
Official title: Growth and the Effect of Genotropin in Chronically Ill Children With Juvenile Rheumatoid Arthritis and With Crohn's Disease
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Arthritis, Juvenile Rheumatoid
Crohn Disease
Keywords: growth hormone
short stature
growth failure
chronic illness
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-08-03
Enrollment: 10
Sex: ALL
Minimum age (years): 5
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The investigators hypothesize that the anabolic effects of Genotropin (somatropin) will improve the height and weight of children with inflammatory based chronic illness who have failed to grow despite receiving adequate nutrition. The investigators will test the hypothesis by treating 32 chronically ill children (16 JRA and 16 Crohn's) with growth hormone (GH) for 12 months and comparing them to baseline.

Detailed description: 1. To determine the effect of GenotropinTM on height, height velocity, body weight and lean body mass. Growth records from previous years will be assessed to determine growth velocity and weight gain. We will measure height and weight during the study using a standardized stadiometer and scale. These parameters will be converted to Z scores (GenenCalcTM, Genentech). Lean body mass (LBM) will be measured by DXA every six months. This specific aim tests the hypothesis that GH significantly improves height, height velocity, weight, weight velocity and LBM in chronically ill children who have grown poorly despite adequate nutritional rehabilitation.
2. To determine the effect of GenotropinTM on whole body protein turnover (WBPT), IGF-1 levels and cytokines. Utilizing the stable isotope 1-\[13C\] leucine, we will measure WBPT. Measurements of WBPT will be correlated with LBM and changes in height and weight velocity. This data will be compared to that from age matched normal children (archival data maintained by the PI). We will measure IGF-1 and the cytokines TNF-α, IL-6 and IL-10 at baseline and very six months. These measures will be correlated with height and weight velocity and IGF-1 levels. Cytokine levels will also be correlated with protein catabolism. This specific aim tests the hypothesis that chronically ill children have increased catabolism, caused by high levels of circulating cytokines and low levels of IGF-1, and that these abnormalities improve with GenotropinTM.
3. Evaluation of bone mineral content (BMC) and bone turnover. At baseline and every six months we will measure BMC of the whole body, hip and spine using DXA. Results will be compared to those from age-matched normal children whose results are archived in the body composition laboratory of Dr. Ken Ellis (Children's Nutrition Research Center, Houston). At baseline and every six months we will also measure bone mineral turnover markers including: osteocalcin, bone specific alkaline phosphatase activity, and deoxypyridinoline. All findings will be related to cytokine levels and to use of glucocorticoids. This specific aim tests the hypothesis that bone density is low in chronically ill children secondary to increased osteoclast activity correlating with elevated cytokine levels.

Eligibility criteria: Inclusion Criteria:

1. Referral for continued poor growth (growth velocity less than the 25th percentile)
2. Height less than the 10th percentile
3. Weight less than the 10th percentile compared to age and gender- matched normal values.

Exclusion Criteria:

1. Previous diagnosis with diabetes, chronic fevers (temp \> 101.5) or chronic bacterial infection
2. Previous treatment with GH
3. Bone age \> 17

Primary outcomes:
measure: The Primary Outcome Variables Will be Height and Weight Z Score.
timeFrame: 12 months
Secondary outcomes:
measure: Secondary Outcome Variables Will Include Change in Lean Body Mass, Change in Bone Mineral Content, Change in Inflammatory Mediated Cytokine Levels and Change in Bone Turnover.
timeFrame: 12 months
Other outcomes:
Locations:
city: Columbus
country: United States
facility: Columbus Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: Dana S Hardin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bechtold S, Ripperger P, Muhlbayer D, Truckenbrodt H, Hafner R, Butenandt O, Schwarz HP. GH therapy in juvenile chronic arthritis: results of a two-year controlled study on growth and bone. J Clin Endocrinol Metab. 2001 Dec;86(12):5737-44. doi: 10.1210/jcem.86.12.8083.
citation: Mauras N, George D, Evans J, Milov D, Abrams S, Rini A, Welch S, Haymond MW. Growth hormone has anabolic effects in glucocorticosteroid-dependent children with inflammatory bowel disease: a pilot study. Metabolism. 2002 Jan;51(1):127-35. doi: 10.1053/meta.2002.28972.
citation: Hardin DS, Ellis KJ, Dyson M, Rice J, McConnell R, Seilheimer DK. Growth hormone decreases protein catabolism in children with cystic fibrosis. J Clin Endocrinol Metab. 2001 Sep;86(9):4424-8. doi: 10.1210/jcem.86.9.7822.
citation: Hardin DS, Rice J, Doyle ME, Pavia A. Growth hormone improves protein catabolism and growth in prepubertal children with HIV infection. Clin Endocrinol (Oxf). 2005 Sep;63(3):259-62. doi: 10.1111/j.1365-2265.2005.02331.x.
citation: Hardin DS, Adams-Huet B, Brown D, Chatfield B, Dyson M, Ferkol T, Howenstine M, Prestidge C, Royce F, Rice J, Seilheimer DK, Steelman J, Shepherds R. Growth hormone treatment improves growth and clinical status in prepubertal children with cystic fibrosis: results of a multicenter randomized controlled trial. J Clin Endocrinol Metab. 2006 Dec;91(12):4925-9. doi: 10.1210/jc.2006-1101. Epub 2006 Oct 3.