Arthritis, Juvenile Rheumatoid, Crohn Disease
Conditions
Keywords
growth hormone, short stature, growth failure, chronic illness
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.
Interventions
DRUGsomatropin [rDNA origin] for injection
Genotropin will be started at 0.3 mg/kg/week administered by daily subcutaneous injection. Doses will be increased by weight at each visit. Additionally, we will monitor IGF-1 levels at month 3, and 6 and adjust the Genotropin dose to maintain IGF-1 levels in the 50th -75th percentile for ages.
Sponsors
Pfizer
Nationwide Children's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
5 Years to 17 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The Primary Outcome Variables Will be Height and Weight Z Score. | 12 months |
Secondary
| Measure | Time frame |
|---|---|
| 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. | 12 months |
Countries
United States
Participant flow
Pre-assignment details
PI left institution suddenly in 2010 and studies were closed. Study records for participants cannot be located and possibly have been destroyed.
Participants by arm
| Arm | Count |
|---|---|
| Somatropin somatropin \[rDNA origin\] for injection: Genotropin will be started at 0.3 mg/kg/week administered by daily subcutaneous injection. Doses will be increased by weight at each visit. Additionally, we will monitor IGF-1 levels at month 3, and 6 and adjust the Genotropin dose to maintain IGF-1 levels in the 50th -75th percentile for ages. | 0 |
| Total | 0 |
Baseline characteristics
| Characteristic | — |
|---|---|
| Region of Enrollment United States | — participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
The Primary Outcome Variables Will be Height and Weight Z Score.
Time frame: 12 months
Population: PI left institution suddenly in 2010 and studies were closed. Study records for participants cannot be located and possibly have been destroyed.
Secondary
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.
Time frame: 12 months
Population: PI left institution suddenly in 2010 and studies were closed. Study records for participants cannot be located and possibly have been destroyed.