Crohn DiseasePhase 2/3NCT00764699
Effect of Increlex® on Children With Crohn Disease
A Phase 2/3 study testing rhIGF (Increlex) in people with Crohn Disease, run by Nationwide Children's Hospital at 1 site in United States.
Trial summary
Patients with Crohn disease often have poor weight gain and short stature, yet the etiology of the poor growth is not well defined. Studies in chronically ill patients who do not have Crohn disease have suggested that inflammation causes IGF-1 deficiency due to inadequate IGF-1 generation. Read more about this study
- Who is it for?
- Ages 5 to 15 years
- Conditions the study is for
- Crohn Disease
- What is being tested?
- rhIGF (Increlex)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2008to May 2010
- Phase
- Phase 2/3
- 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 5 to 15 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Moderate to severe Crohn Disease (PCDAI > 30)
- Chronological age 5-15 years old
- Tanner 1 - 3
- Bone age less than or equal to 13 in females and 14 in males
Who cannot join
- Identified infectious etiology
- Immunological disorder (excluding Crohn disease)
- Associated severe concomitant chronic illnesses (CF, liver failure, etc)
Trial locations and contacts
1 site in 1 country.
United States1 site
Nationwide Children's Hospital
Columbus, Ohio, 43205
About this study
Patients with Crohn disease often have poor weight gain and short stature, yet the etiology of the poor growth is not well defined. Studies in chronically ill patients who do not have Crohn disease have suggested that inflammation causes IGF-1 deficiency due to inadequate IGF-1 generation. Previous studies of GH use in Crohn patients have demonstrated improvement in linear growth, weight and bone mineralization. However, GH can cause glucose intolerance in chronically ill children, particularly those who require treatment with corticosteroids. Recently the FDA has approved recombinant IGF-1 (rhIGF) for treatment of IGF-1 deficient short stature. This medication has not been studied in Crohn disease. The purpose of this study is to test the hypothesis that poor growth in Crohn disease is associated abnormal IGF-1 generation which leads to poor linear growth, decreased weight and osteoporosis and that replacement of IGF-1 with rhIGF will correct growth and improve bone density. To test our hypothesis we will recruit 20 patients with Crohn disease from our pediatric gastroenterology practice. Each will have been previously diagnosed with Crohn disease for a minimum of one year and will be studied at baseline and six month intervals for one year while on treatment with Increlex.
Read the detailed description
- Subjects. We will recruit 20 established Crohn patients from our gastroenterology (GI) referral practice at Nationwide Children's Hospital in Columbus, Ohio. Each will have previously undergone a complete diagnostic workup and classification of disease. Information on disease activity, location and behavior are routinely recorded at each follow up visit. Medical records will be assessed for this information. These patients will be followed every three months. All of these patients will be assigned to receive rhIGF therapy for 12 months and results will be compared to medical record data. We will recruit 10 per year.
- Assessment of growth and IGF-1 generation. Each subject will undergo IGF-1 generation testing using standard published "high-dose: protocol and interpreted according to guidelines of Blum. Briefly, GH will be given as a one time per day subcutaneous injection in a dose of 0.05mg/kg/dy. IGF-1 will be measured at baseline and again after 7 days. Inadequate generation will be interpreted by an IGF-1 increase < 15 ng/dl after 7 days of GH. We will also measure baseline random GH and IGFBP-3 levels. The IGF-1, GH and IGFBP-3 levels will be measured by Esoterix laboratory (Calabasas Hills, CA). IGF-1 levels will also be measured every six months and with disease exacerbation. All patients will have a single radiological film of the left hand and wrist to determine bone age by Greulich and Pyle standards, and routine examination by the PI to determine Tanner staging.
- Anthropometric measures. Patients will be seen every three months. At every visit, we will evaluate linear growth using a calibrated stadiometer and weight with a standardized scale. Longitudinal data will be used to calculate height and weight velocity. Height velocity will be annualized for each visit compared to baseline data. All growth information, including velocity will be converted to standard deviation scores (SDS, Z score) using GenenCalc (Genentech, San Francisco, CA).
- Nutrition. To assess for low nutritional intake as the cause for poor growth (and low IGF-1 levels), each patient will complete a 3 day food journal at every visit and results will be assessed by Nutrition Pro software. We will evaluate our findings in both pubertal and prepubertal children. For this reason we will carefully measure Tanner stage as breast in girls and testicular volume in boys. We will measure testosterone levels in boys and estradiol in girls (Esoterix). Sex steroid levels will be correlated with Tanner staging and tempo of pubertal progression.
- Treatment with rhIGF (Increlex, Tercica). Patients will be followed as above for 12 months while on Increlex therapy. Increlex (rhIGF) will be administered per the following schema: First 2 weeks: 40 mcg/kg BID; Weeks 3 and 4: 80 mcg/kg BID; Subsequent weeks: 120 mcg/kg BID. Each parent and patient will be carefully trained in injection technique by the same skilled personnel. Compliance will be assessed by having subjects return empty vials to the study site.
- Bone mineral content and bone turnover. All subjects will undergo DXA scan (Lunar Prodigy) at baseline and every six months. Measurements will be compared to age- and gender- matched normals and converted to Z scores (www.bcm.edu/bodycomplab). To determine bone turnover, blood and urine will be collected at baseline and every six months. These labs will be run by Esoterix according to their methods: N-Telopeptides (reverse transcriptase PCR, urine), osteocalcin (double antibody RIA, blood), bone specific alkaline phosphatase activity (ICMA, blood), and deoxypyridinoline (ELISA, urine). Although the typical patient treated with GH demonstrates initial bone loss during the first six months, our group has documented improvement in bone mineral content within six months of starting GH therapy.
- Cytokines. We will measure the cytokines TNF-α, IL-1, and IL-6 at the initiation of the study, at 6 months and 12 months. This will better help us understand the role of cytokines on disease course, activity, and the growth hormone axis.
- Biomarkers for rhIGF-1 dosing efficacy. We will draw BL, 6 mos and 12 mos levels of IGF-1, IGFBP3 and ALS levels. The baseline level will be collected prior to the 1st dose of Increlex. At six months patients will be instructed to take their Increlex the morning of their visit and the sample will be drawn within 2 hours of dosing which will represent peak biomarker levels. The 12 month level will be obtained in the morning the day after the patient completes his/her final dose and will represent a trough level.
- Measures of Disease Activity. At each protein turnover measure we will ask subjects to bring stool samples which will be evaluated for fecal calprotectin. We will complete the Pediatric Crohn Disease Activity Index (PCDAI), a reliable and valid index for disease activity in clinical research. Subjects will complete the IMPACT-III, a valid and reliable measure of quality of life in pediatric Crohn disease.
- Conditions
- Crohn Disease
- Being tested
- rhIGF (Increlex)
- Keywords
- poor growth, inflammatory bowel disease
- Medical subject headings
- Crohn Disease, Inflammatory Bowel Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhIGF (Increlex)Drug
Also called Increlex
rhIGF will be administered as a subcutaneous injection per the following schema: First 2 weeks: 40 mcg/kg BID; Weeks 3 and 4: 80 mcg/kg BID; Subsequent weeks: 120 mcg/kg BID.
| Study group | Role | What they receive |
|---|---|---|
| rhIGF | Experimental | Treatment with rhIGF (Increlex) Receives: Drug: rhIGF (Increlex) |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Primary Outcome Variable for the Monitoring Study (Baseline, Six Months and Disease Exacerbation) Will be Longitudinal Growth as Measured by Height Velocity
Measured: Six months and 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Oct 2008 (estimated)
- Study startOct 2008
- Primary completionMay 2010
- Study completionMay 2010
Why it stopped: PI left institution
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 (4)Papers the sponsor has linked to this study.
- Other trials for Crohn DiseaseStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 3 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Tercica
- Responsible party
- Sponsor
- Investigators
- Dana S. Hardin, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00764699
- Sponsor's protocol ID
- IRB08-00213
- Status last verified
- Feb 2018
- First submitted
- 1 Oct 2008
- Last updated
- 2 Mar 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Cezard JP, Touati G, Alberti C, Hugot JP, Brinon C, Czernichow P. Growth in paediatric Crohn's disease. Horm Res. 2002;58 Suppl 1:11-5. doi: 10.1159/000064759.
PubMed 12373007Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS. Growth, body composition, and nutritional status in children and adolescents with Crohn's disease. J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):33-40. doi: 10.1097/00005176-200007000-00009.
PubMed 10896068Hardin 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.
PubMed 16117811Mauras 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.
PubMed 11782884
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Increlex® on Children With Crohn Disease
- ClinicalTrials.gov ID
- NCT00764699
- Acronym / sponsor ID
- IRB08-00213
- Conditions
- Crohn Disease
- Keywords
- poor growth, inflammatory bowel disease
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI left institution
- Enrolment
- 3 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- Tercica
- Study start
- Oct 2008
- Primary completion
- May 2010 (actual)
- Study completion
- May 2010 (actual)
- First posted
- 2 Oct 2008 (estimated)
- Results
- Posted 2 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Patients with Crohn disease often have poor weight gain and short stature, yet the etiology of the poor growth is not well defined. Studies in chronically ill patients who do not have Crohn disease have suggested that inflammation causes IGF-1 deficiency due to inadequate IGF-1 generation. Previous studies of GH use in Crohn patients have demonstrated improvement in linear growth, weight and bone mineralization. However, GH can cause glucose intolerance in chronically ill children, particularly those who require treatment with corticosteroids. Recently the FDA has approved recombinant IGF-1 (rhIGF) for treatment of IGF-1 deficient short stature. This medication has not been studied in Crohn disease. The purpose of this study is to test the hypothesis that poor growth in Crohn disease is associated abnormal IGF-1 generation which leads to poor linear growth, decreased weight and osteoporosis and that replacement of IGF-1 with rhIGF will correct growth and improve bone density. To test our hypothesis we will recruit 20 patients with Crohn disease from our pediatric gastroenterology practice. Each will have been previously diagnosed with Crohn disease for a minimum of one year and will be studied at baseline and six month intervals for one year while on treatment with Increlex.
Detailed description
- Subjects. We will recruit 20 established Crohn patients from our gastroenterology (GI) referral practice at Nationwide Children's Hospital in Columbus, Ohio. Each will have previously undergone a complete diagnostic workup and classification of disease. Information on disease activity, location and behavior are routinely recorded at each follow up visit. Medical records will be assessed for this information. These patients will be followed every three months. All of these patients will be assigned to receive rhIGF therapy for 12 months and results will be compared to medical record data. We will recruit 10 per year.
- Assessment of growth and IGF-1 generation. Each subject will undergo IGF-1 generation testing using standard published "high-dose: protocol and interpreted according to guidelines of Blum. Briefly, GH will be given as a one time per day subcutaneous injection in a dose of 0.05mg/kg/dy. IGF-1 will be measured at baseline and again after 7 days. Inadequate generation will be interpreted by an IGF-1 increase < 15 ng/dl after 7 days of GH. We will also measure baseline random GH and IGFBP-3 levels. The IGF-1, GH and IGFBP-3 levels will be measured by Esoterix laboratory (Calabasas Hills, CA). IGF-1 levels will also be measured every six months and with disease exacerbation. All patients will have a single radiological film of the left hand and wrist to determine bone age by Greulich and Pyle standards, and routine examination by the PI to determine Tanner staging.
- Anthropometric measures. Patients will be seen every three months. At every visit, we will evaluate linear growth using a calibrated stadiometer and weight with a standardized scale. Longitudinal data will be used to calculate height and weight velocity. Height velocity will be annualized for each visit compared to baseline data. All growth information, including velocity will be converted to standard deviation scores (SDS, Z score) using GenenCalc (Genentech, San Francisco, CA).
- Nutrition. To assess for low nutritional intake as the cause for poor growth (and low IGF-1 levels), each patient will complete a 3 day food journal at every visit and results will be assessed by Nutrition Pro software. We will evaluate our findings in both pubertal and prepubertal children. For this reason we will carefully measure Tanner stage as breast in girls and testicular volume in boys. We will measure testosterone levels in boys and estradiol in girls (Esoterix). Sex steroid levels will be correlated with Tanner staging and tempo of pubertal progression.
- Treatment with rhIGF (Increlex, Tercica). Patients will be followed as above for 12 months while on Increlex therapy. Increlex (rhIGF) will be administered per the following schema: First 2 weeks: 40 mcg/kg BID; Weeks 3 and 4: 80 mcg/kg BID; Subsequent weeks: 120 mcg/kg BID. Each parent and patient will be carefully trained in injection technique by the same skilled personnel. Compliance will be assessed by having subjects return empty vials to the study site.
- Bone mineral content and bone turnover. All subjects will undergo DXA scan (Lunar Prodigy) at baseline and every six months. Measurements will be compared to age- and gender- matched normals and converted to Z scores (www.bcm.edu/bodycomplab). To determine bone turnover, blood and urine will be collected at baseline and every six months. These labs will be run by Esoterix according to their methods: N-Telopeptides (reverse transcriptase PCR, urine), osteocalcin (double antibody RIA, blood), bone specific alkaline phosphatase activity (ICMA, blood), and deoxypyridinoline (ELISA, urine). Although the typical patient treated with GH demonstrates initial bone loss during the first six months, our group has documented improvement in bone mineral content within six months of starting GH therapy.
- Cytokines. We will measure the cytokines TNF-α, IL-1, and IL-6 at the initiation of the study, at 6 months and 12 months. This will better help us understand the role of cytokines on disease course, activity, and the growth hormone axis.
- Biomarkers for rhIGF-1 dosing efficacy. We will draw BL, 6 mos and 12 mos levels of IGF-1, IGFBP3 and ALS levels. The baseline level will be collected prior to the 1st dose of Increlex. At six months patients will be instructed to take their Increlex the morning of their visit and the sample will be drawn within 2 hours of dosing which will represent peak biomarker levels. The 12 month level will be obtained in the morning the day after the patient completes his/her final dose and will represent a trough level.
- Measures of Disease Activity. At each protein turnover measure we will ask subjects to bring stool samples which will be evaluated for fecal calprotectin. We will complete the Pediatric Crohn Disease Activity Index (PCDAI), a reliable and valid index for disease activity in clinical research. Subjects will complete the IMPACT-III, a valid and reliable measure of quality of life in pediatric Crohn disease.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| rhIGF | Experimental | Drug: rhIGF (Increlex)Treatment with rhIGF (Increlex) |
Who may qualify
- Ages
- 5 to 15 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Moderate to severe Crohn Disease (PCDAI > 30)
- Chronological age 5-15 years old
- Tanner 1 - 3
- Bone age less than or equal to 13 in females and 14 in males
Key exclusion criteria (3 listed)
- Identified infectious etiology
- Immunological disorder (excluding Crohn disease)
- Associated severe concomitant chronic illnesses (CF, liver failure, etc)
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 |
|---|---|---|
| rhIGF (Increlex)Also: IncrelexrhIGF will be administered as a subcutaneous injection per the following schema: First 2 weeks: 40 mcg/kg BID; Weeks 3 and 4: 80 mcg/kg BID; Subsequent weeks: 120 mcg/kg BID. | Drug | rhIGF |
Primary outcome
The Primary Outcome Variable for the Monitoring Study (Baseline, Six Months and Disease Exacerbation) Will be Longitudinal Growth as Measured by Height Velocity
Time frame: Six months and 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 12373007Cezard JP, Touati G, Alberti C, Hugot JP, Brinon C, Czernichow P. Growth in paediatric Crohn's disease. Horm Res. 2002;58 Suppl 1:11-5. doi: 10.1159/000064759.
- Background: PubMed 10896068Sentongo TA, Semeao EJ, Piccoli DA, Stallings VA, Zemel BS. Growth, body composition, and nutritional status in children and adolescents with Crohn's disease. J Pediatr Gastroenterol Nutr. 2000 Jul;31(1):33-40. doi: 10.1097/00005176-200007000-00009.
- Background: PubMed 16117811Hardin 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.
- Background: PubMed 11782884Mauras 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.
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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.
Dana S. Hardin, MD principal investigator
Nationwide Children's Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing rhIGF (Increlex) in people with Crohn Disease, run by Nationwide Children's Hospital at 1 site 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 4 inclusion and 3 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: stopped early, as of the sponsor's last update on 2 Mar 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 2 Mar 2018). 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 Primary Outcome Variable for the Monitoring Study (Baseline, Six Months and Disease Exacerbation) Will be Longitudinal Growth as Measured by Height Velocity (time frame: Six months and 1 year). 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 NCT00764699, which also lists 4 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 2 Mar 2018.