Effect of Increlex® on Children With Crohn Disease

February 23, 2018 updated by: Nationwide Children's Hospital
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

  1. 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.
  2. 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.
  3. 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).
  4. 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.
  5. 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.
  6. 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.
  7. 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.
  8. 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.
  9. 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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
3

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Ohio
      • Columbus, Ohio, United States, 43205
        • Nationwide Children's Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 11 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • Identified infectious etiology
  • Immunological disorder (excluding Crohn disease)
  • Associated severe concomitant chronic illnesses (CF, liver failure, etc)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: rhIGF
Treatment with rhIGF (Increlex)
Drug: rhIGF (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.
Other Names:
  • Increlex

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
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
Six months and 1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Nationwide Children's Hospital

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Tercica

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Dana S. Hardin, MD, The Research Institute at Nationwide Children's Hospital

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 1, 2008

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
May 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
October 1, 2008

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 1, 2008

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 2, 2008

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2018

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 23, 2018

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB08-00213

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