A Study to Optimize Growth Hormone Dosing in Children With Chronic Kidney Disease by Measuring IGF-1 Levels in Blood

Kidney Failure, Chronic Clinical Trial

Official title:

IGF-1 Generation Test in Children With Chronic Kidney Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00212758
• Other study ID #: Genentech # 303-MO1
• Status: Completed
• Phase: Phase 4
• First received: September 14, 2005
• Last updated: October 22, 2011
• Start date: January 2005
• Est. completion date: May 2010

Study information

• Verified date: October 2011
• Source: Oregon Health and Science University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: May 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 2 Years to 18 Years

Eligibility

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.

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Dwarfism, Pituitary
• Growth Hormone Deficiency
• Kidney Diseases
• Kidney Failure, Chronic
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Nutropin AQ
Nutropin AQ

Locations

Country	Name	City	State
United States	Texas Children's Hospital	Houston	Texas
United States	UT Houston Medical School	Houston	Texas
United States	Loma Linda UMC & Children's Hospital	Loma Linda	California
United States	University of California in Los Angeles (UCLA)	Los Angeles	California
United States	Legacy Emanuel Children's Hospital	Portland	Oregon
United States	Oregon Health & Science University	Portland	Oregon
United States	University of Washington, Children's Hospital & Regional Medical Center	Seattle	Washington
United States	Stanford University Medical Center	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Oregon Health and Science University	Genentech, Inc.

Country where clinical trial is conducted

United States, 

References & Publications (1)

Buckway CK, Guevara-Aguirre J, Pratt KL, Burren CP, Rosenfeld RG. The IGF-I generation test revisited: a marker of GH sensitivity. J Clin Endocrinol Metab. 2001 Nov;86(11):5176-83. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
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).	Day 1 & Day 8	No
Secondary	Change in Height at 56 Weeks		week 1, week 56	No