Kidney Failure, ChronicPhase 4NCT00212758
A Study to Optimize Growth Hormone Dosing in Children With Chronic Kidney Disease by Measuring IGF-1 Levels in Blood
A Phase 4 study testing Nutropin AQ in people with Kidney Failure, Chronic and Growth Hormone Deficiency, run by Oregon Health and Science University at 8 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 2 to 18 years
- Conditions the study is for
- Kidney Failure, Chronic, Growth Hormone Deficiency
- What is being tested?
- Nutropin AQ
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 17 participants
- Where
- 8 sitesUnited States
- Study dates
- Jan 2005to May 2010
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Texas Children's Hospital
Houston, Texas, 77030
UT Houston Medical School
Houston, Texas, 77030
Loma Linda UMC & Children's Hospital
Loma Linda, California, 92350
University of California in Los Angeles (UCLA)
Los Angeles, California, 90095-1752
Legacy Emanuel Children's Hospital
Portland, Oregon, 97227
Oregon Health & Science University
Portland, Oregon, 97239
University of Washington, Children's Hospital & Regional Medical Center
Seattle, Washington, 98105
Stanford University Medical Center
Stanford, California, 94305-5208
About this study
Official title: IGF-1 Generation Test in Children With Chronic Kidney Disease
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.
Read the 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.
- Conditions
- Kidney Failure, Chronic, Growth Hormone Deficiency
- Being tested
- Nutropin AQ
- Keywords
- Short stature, children, kidney failure, chronic, Growth
- Medical subject headings
- Kidney Failure, Chronic, Dwarfism, Pituitary, Dwarfism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nutropin AQDrug
Also called Growth hormone
Nutropin AQ
| Study group | Role | What they receive |
|---|---|---|
| Low- Standard GH dose | Active comparator | This arm will receive Low dose of growth hormone (GH) (Nutropin AQ), for 7 days in a cross over design. Low dose GH will be 0.025 mg/kg/day. This will be followed by 2 weeks of wash out, then subjects will receive and the standard dose of Nutropin AQ (GH) at 0.05 mg/kg/dose given subcutaneously for another 7 days. IGF-I levels are measured after 7 days of the Low and the Standard dose of GH. After that all subjects will be treated with the standard dose of GH therapy of 0.05 mg/kg/day for 6 months and re-evaluated. If growth is adequate then subjects will continue on standard dose of GH for another 6 months for a total of 12 months. Receives: Drug: Nutropin AQ |
| Standard-Low GH dose (7 Days) | Active comparator | This arm will receive Standard dose of growth hormone (GH) (Nutropin AQ), for 7 days in a cross over design. Standard dose GH will be 0.5 mg/kg/day. This will be followed by 2 weeks of wash out, then subjects will receive and the Low dose of Nutropin AQ (GH) at 0.025 mg/kg/dose given subcutaneously for another 7 days. IGF-I levels are measured after 7 days of the Low and the Standard dose of GH. After that all subjects will be treated with the standard dose of GH therapy of 0.05 mg/kg/day for 6 months and re-evaluated. If growth is adequate then subjects will continue on standard dose of GH for another 6 months for a total of 12 months. Receives: Drug: Nutropin AQ |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1 & Day 8
Secondary outcomes (1)
Change in Height at 56 Weeks
Measured: week 1, week 56
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2005 (estimated)
- Study startJan 2005
- Primary completionMay 2008
- Study completionMay 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Kidney Failure, ChronicStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Collaborators
- Genentech, Inc.
- Responsible party
- Principal investigator, Amira Al-Uzri, Oregon Health and Science University
- Investigators
- Amira Y Al-Uzri, M.D., Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00212758
- Sponsor's protocol ID
- Genentech # 303-MO1
- Status last verified
- Oct 2011
- First submitted
- 14 Sep 2005
- Last updated
- 26 Oct 2011
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
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. doi: 10.1210/jcem.86.11.8019.
PubMed 11701674Al-Uzri A, Swinford RD, Nguyen T, Jenkins R, Gunsul A, Kachan-Liu SS, Rosenfeld R. The utility of the IGF-I generation test in children with chronic kidney disease. Pediatr Nephrol. 2013 Dec;28(12):2323-33. doi: 10.1007/s00467-013-2570-0. Epub 2013 Sep 7.
PubMed 24013497
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- IGF-1 Generation Test in Children With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00212758
- Acronym / sponsor ID
- Genentech # 303-MO1
- Conditions
- Kidney Failure, Chronic, Growth Hormone Deficiency
- Keywords
- Short stature, children, kidney failure, chronic, Growth
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Collaborators
- Genentech, Inc.
- Study start
- Jan 2005
- Primary completion
- May 2008 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 21 Sep 2005 (estimated)
- Results
- Posted 26 Oct 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Low- Standard GH dose | Active comparator | Drug: Nutropin AQThis arm will receive Low dose of growth hormone (GH) (Nutropin AQ), for 7 days in a cross over design. Low dose GH will be 0.025 mg/kg/day. This will be followed by 2 weeks of wash out, then subjects will receive and the standard dose of Nutropin AQ (GH) at 0.05 mg/kg/dose given subcutaneously for another 7 days. IGF-I levels are measured after 7 days of the Low and the Standard dose of GH. After that all subjects will be treated with the standard dose of GH therapy of 0.05 mg/kg/day for 6 months and re-evaluated. If growth is adequate then subjects will continue on standard dose of GH for another 6 months for a total of 12 months. |
| Standard-Low GH dose (7 Days) | Active comparator | Drug: Nutropin AQThis arm will receive Standard dose of growth hormone (GH) (Nutropin AQ), for 7 days in a cross over design. Standard dose GH will be 0.5 mg/kg/day. This will be followed by 2 weeks of wash out, then subjects will receive and the Low dose of Nutropin AQ (GH) at 0.025 mg/kg/dose given subcutaneously for another 7 days. IGF-I levels are measured after 7 days of the Low and the Standard dose of GH. After that all subjects will be treated with the standard dose of GH therapy of 0.05 mg/kg/day for 6 months and re-evaluated. If growth is adequate then subjects will continue on standard dose of GH for another 6 months for a total of 12 months. |
Who may qualify
- Ages
- 2 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- 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.
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nutropin AQAlso: Growth hormoneNutropin AQ | Drug | Low- Standard GH dose, Standard-Low GH dose (7 Days) |
Primary outcome
The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1)
Time frame: Day 1 & Day 8
We will measure the amount of serum IGF-I generated after 7 days of growth hormone therapy (Day8-Day1).
1 secondary outcome
Change in Height at 56 Weeks
Time frame: week 1, week 56
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2011.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 11701674Buckway 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. doi: 10.1210/jcem.86.11.8019.
- Derived from this study: PubMed 24013497Al-Uzri A, Swinford RD, Nguyen T, Jenkins R, Gunsul A, Kachan-Liu SS, Rosenfeld R. The utility of the IGF-I generation test in children with chronic kidney disease. Pediatr Nephrol. 2013 Dec;28(12):2323-33. doi: 10.1007/s00467-013-2570-0. Epub 2013 Sep 7.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Amira Y Al-Uzri, M.D. principal investigator
Oregon Health and Science University
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Nutropin AQ in people with Kidney Failure, Chronic and Growth Hormone Deficiency, run by Oregon Health and Science University at 8 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Oct 2011. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The Change in Amount of Insulin Like Growth Factor (IGF-I) Generated (Day 8-day 1) (time frame: Day 1 & Day 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00212758, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2011.