Growth Hormone Deficiency, Kidney Failure, Chronic
Conditions
Keywords
Short stature, children, kidney failure, chronic, Growth
Brief 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.
Detailed description
The study will involve 30 children with chronic kidney disease and failure to grow. The study will last for 14 months. There will be a screening clinic visit if the child qualifies for the study, Week -8. Each clinic visit will include, getting a medical history, a physical exam, and a blood test. Also an x-ray of the wrist to calculate bone age. If abnormal blood values are found as a result of kidney failure then an attempt will be made to correct them over the next 2 months before enrollment in the study. Also children will be asked to keep track of all of the foods for 3 days every month during the study. A study nutritionist will call them once each month to go over the food diary. At study Week -4, children will come again for a clinic visit. Then at Week 0 of the study, a decision will be made randomly based on the level of kidney function to what dose of growth hormone a child will receive. This will be either a low dose of growth hormone or a high dose of growth hormone. At the Week 1 and Week 4 visits, children will come for a clinic visit. Children will take growth hormone (through a needle under the skin) every night for a full 7 days during each of the two weeks. In the mornings before the 1st and after the 7th dose both weeks, children will have their blood drawn to check IGF-1 levels. During Weeks 2 and 3, children will not take any growth hormone in order to allow the body to clear, or wash-out, the medication from the system before Week 4. At Week 5, children will begin taking growth hormone each evening and continue to do so every day through Week 28. Then, for Weeks 29 and 30, children will have another wash-out period with no growth hormone treatment. At Week 31, blood will be drawn in the mornings before the 1st and after the 7th dose of growth hormone treatment. From Week 32 on, children will take growth hormone every evening and continue to do so through Week 56, the end of the study. Also at week 1, skin fold measurements to assess body fat will be done on all subjects. A DEXA scan, a test that measures body fat and muscle mass will be done on the older children in the study on an optional basis on Weeks 1, 28 and 56. Another wrist X-ray for bone age will be repeated at 56 weeks of the study.
Interventions
DRUGNutropin AQ
Nutropin AQ
Sponsors
Genentech, Inc.
Oregon Health and Science University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 18 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1) | Day 1 & Day 8 | We will measure the amount of serum IGF-I generated after 7 days of growth hormone therapy (Day8-Day1). |
Secondary
| Measure | Time frame |
|---|---|
| Change in Height at 56 Weeks | week 1, week 56 |
Countries
United States
Participant flow
Recruitment details
This is a multicenter trial. Patients were recruited from pediatric nephrology clinics at various centers.
Pre-assignment details
A two month run-in period was implemented to stabilize subjects and correct any metabolic abnormalities that may affect growth. This two month period may be waived per the center PI if patient was deemed stable. Patients were randomized to either a low or standard dose of GH (Nutropin AQ)used in the IGF-I generation.
Participants by arm
| Arm | Count |
|---|---|
| All Participants Subjects will be randomized to either a low or standard arm. The low dose will get 0.025 mg/kg/day of growth hormone therapy and the standard dose arm will receive 0.05 mg/kg/dose given subcutaneously. After one week of therapy and 2 weeks of wash out, subjects will change the dose of GH therapy and will receive the alternate dose for another week. After that all subjects will be treated with the standard dose of GH therapy of 0.05 mg/kg/day for 6 months, re-evaluate growth velocity and then continue for another 6 months on GH. | 17 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Standard Therapy of GH (12 Months) | Adverse Event | 1 | 0 |
| Standard Therapy of GH (12 Months) | Lost to Follow-up | 1 | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 17 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 7.6 years STANDARD_DEVIATION 4 |
| Region of Enrollment United States | 17 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 |
Outcome results
Primary
The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1)
We will measure the amount of serum IGF-I generated after 7 days of growth hormone therapy (Day8-Day1).
Time frame: Day 1 & Day 8
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose GH | The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1) | 115 mcg/L | Standard Deviation 104 |
| Standard Dose GH | The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1) | 129 mcg/L | Standard Deviation 112 |
Secondary
Change in Height at 56 Weeks
Time frame: week 1, week 56
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Low Dose GH | Change in Height at 56 Weeks | 10.3 cm | Standard Deviation 1.1 |