Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

This study has been completed.

Sponsor:

Collaborator:

Genentech

Information provided by (Responsible Party):

Children's Hospital Medical Center, Cincinnati

ClinicalTrials.gov Identifier:

NCT00109473

First received: April 28, 2005

Last updated: October 10, 2011

Last verified: October 2011

History of Changes

Results First Received: June 24, 2011

Study Type:	Interventional
Study Design:	Allocation: Randomized; Endpoint Classification: Efficacy Study; Intervention Model: Parallel Assignment; Masking: Open Label; Primary Purpose: Treatment
Condition:	Crohn's Disease
Interventions:	Drug: growth hormone Drug: cortecosteroid

Participant Flow

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Recruitment Details

Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
98 subjects were assessed for eligibility, 76 did not meet inclusion criteria, 21 refused to participate

Pre-Assignment Details

Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
21 subjects enrolled, one withdrew consent prior to randomization.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Participant Flow for 3 periods

Period 1: Baseline (0 Through 12 Weeks)

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
STARTED	10 ^[1]	10
Analyzed	10	10
COMPLETED	10	9 ^[2]
NOT COMPLETED	0	1

[1]	11 subjects allocated to Group A; one withdrew consent, only 10 receieved intervention.
[2]	One subject discontinued intervention because of active disease requiring imfliximab

Period 2: Week 12 to Week 24

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
STARTED	10	9
Analyzed	9	9
COMPLETED	9 ^[1]	9 ^[2]
NOT COMPLETED	1	0

[1]	One subject withdrew consent
[2]	one subject discontinued intervention due to active disease requiring surgery

Period 3: 52 Week Extension Phase

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
STARTED	9	8
Analyzed	9	8
COMPLETED	5 ^[1]	3 ^[1]
NOT COMPLETED	4	5

[1]	Extension phase ends when subjects discontinue intervention due to active disease or reaches week 64

Baseline Characteristics

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Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician
Total	Total of all reporting groups

Baseline Measures

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)	Total
Number of Participants [units: participants]	10	10	20
Age [units: participants]
<=18 years	10	10	20
Age [units: years] Mean ± Standard Deviation	12 ± 3	13 ± 3	13 ± 3
Gender [units: participants]
Female	2	2	4
Male	8	8	16
Region of Enrollment [units: participants]
United States	10	10	20

Outcome Measures

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1. Primary:

Crohn's Disease Histologic Index of Severity (CDHIS) [ Time Frame: Baseline and 12 weeks ]

Measure Type	Primary
Measure Title	Crohn's Disease Histologic Index of Severity (CDHIS)
Measure Description	The CDHIS was developed and validated in order to determine the effect of therapies upon histologic disease activity in Crohn's Disease. It has been used to assess mucosal healing in response to infliximab and 6-MP/AZA.It contains eight items which reflect epithelial injury, mucosal inflammation, and the extent of involvement. Scores range from 0-16, with patients with moderate to severely active CD typically having scores of 6-12. It was computed by a GI pathologist. The higher the score indicates worsening of disease, the lowest score is 0 and highest possible is 16
Time Frame	Baseline and 12 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Crohn's Disease Histologic Index of Severity (CDHIS) [units: scores on a scale] Number ( 95% Confidence Interval )
Baseline	7 ( 5 to 9 )	8 ( 6 to 10 )
Week 12	6 ( 4 to 8 )	8 ( 5 to 10 )

No statistical analysis provided for Crohn's Disease Histologic Index of Severity (CDHIS)

2. Secondary:

Serum IGF-1 (Insulin-like Growth Factor 1)z Score [ Time Frame: Baseline, 12 weeks, 24 weeks ]

Measure Type	Secondary
Measure Title	Serum IGF-1 (Insulin-like Growth Factor 1)z Score
Measure Description	Elevated serum IGF-1 levels have been implicated in the development of colorectal cancer, both in the general population and in patients with an excess of growth hormone production. The serum IGF-1 levels were monitored to maintain them in the physiologic range during growth hormone therapy to reduce the risk of tumorigenesis. The levels are reported as a z score, a statistical way of standardizing data. The standard deviation is the unit of measurement of the z-score. Each z score corresponds to a point in a normal distribution, describing how much a point deviates from a mean.
Time Frame	Baseline, 12 weeks, 24 weeks
Safety Issue	Yes

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Serum IGF-1 (Insulin-like Growth Factor 1)z Score [units: Z score] Mean ± Standard Error
Baseline	-0.4 ± 0.6	-0.7 ± 0.3
Week 12	1.8 ± 1	-1 ± 0.3
Week 24	3.3 ± 1.5	3.8 ± 1

No statistical analysis provided for Serum IGF-1 (Insulin-like Growth Factor 1)z Score

3. Secondary:

IMPACT III Score [ Time Frame: Baseline, 12 weeks, 24 weeks ]

Measure Type	Secondary
Measure Title	IMPACT III Score
Measure Description	Health-related quality of life (QOL)was assessed using the IMPACT 111 questionnnaire. It is a self-administered 35 item questionnaire which typically takes 10-15 minutes to complete. Scores range from 0-350, with higher scores reflecting better perceived quality of life.
Time Frame	Baseline, 12 weeks, 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
IMPACT III Score [units: Scores on a scale] Mean ( 95% Confidence Interval )
Baseline	134 ( 120 to 148 )	132 ( 119 to 146 )
Week 12	143 ( 129 to 157 )	136 ( 123 to 150 )

No statistical analysis provided for IMPACT III Score

4. Secondary:

Pediatric Crohn's Disease Activity Index (PCDAI) [ Time Frame: Baseline, 12 and 24 weeks ]

Measure Type	Secondary
Measure Title	Pediatric Crohn's Disease Activity Index (PCDAI)
Measure Description	The PCDAI is a previously validated measure of clinical disease activity for children with CD. It contains three self-report items which reflect patient abdominal pain, diarrhea, and general well being; three laboratory values; height and weight velocity; and three physical examination parameters reflecting abdominal tenderness, perirectal disease, and extra-intestinal manifestations. Scores may range from 0-100. Remission is defined as 0-10, mild disease as 10-30, and moderate to severe disease as greater than 30.
Time Frame	Baseline, 12 and 24 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Pediatric Crohn's Disease Activity Index (PCDAI) [units: Scores on a scale] Mean ( 95% Confidence Interval )
Baseline	32 ( 20 to 43 )	33 ( 25 to 40 )
Week 12	8 ( 2 to 14 )	22 ( 14 to 30 )
Week 24	9 ( 2 to 14 )	6 ( 1 to 10 )

Statistical Analysis 1 for Pediatric Crohn's Disease Activity Index (PCDAI)

Groups ^[1]	All groups
Method ^[2]	Mixed Models Analysis
P Value ^[3]	0.02
Mean Difference (Final Values) ^[4]	14

[1]	Additional details about the analysis, such as null hypothesis and power calculation:
	No text entered.
[2]	Other relevant information, such as adjustments or degrees of freedom:
	No text entered.
[3]	Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
	No text entered.
[4]	Other relevant estimation information:
	No text entered.

5. Secondary:

Crohn's Disease Endoscopic Index of Severity (CDEIS) [ Time Frame: Baseline and 12 weeks ]

Measure Type	Secondary
Measure Title	Crohn's Disease Endoscopic Index of Severity (CDEIS)
Measure Description	Measure of mucosal disease at baseline and week 12 obtained during colonoscopy. The CDEIS score generally ranges from 0–30. A higher score indicates more severe mucosal inflammation.
Time Frame	Baseline and 12 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Crohn's Disease Endoscopic Index of Severity (CDEIS) [units: Scores on a scale] Mean ( 95% Confidence Interval )
Baseline	9 ( -1 to 18 )	8 ( 2 to 13 )
Week 12	3 ( 1 to 6 )	6 ( 1 to 12 )

No statistical analysis provided for Crohn's Disease Endoscopic Index of Severity (CDEIS)

6. Secondary:

Height Velocity [ Time Frame: Baseline, week 12, 24 and 48 ]

Measure Type	Secondary
Measure Title	Height Velocity
Measure Description	Height velocity was computed every 12 weeks up to week 64 and then yearly during the Maintenance study. Since 40 to 80% of children with Crohn's disease have significant growth failure at diagnosis, height velocity is used to track for changes in height. It is calculated by measuring height at two points of time and then dividing the change by the amount of time.
Time Frame	Baseline, week 12, 24 and 48
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Height Velocity [units: cm/year] Mean ± Standard Error
Baseline	5 ± 1	3 ± 1
Week 12	8 ± 1	3 ± 1
Week 24	9 ± 1	7 ± 1

No statistical analysis provided for Height Velocity

7. Secondary:

Fecal Calprotectin [ Time Frame: At 24 and 64 weeks ]

Measure Type	Secondary
Measure Title	Fecal Calprotectin
Measure Description	Fecal calprotectin is a previously validated stool marker of intestinal inflammation in Crohn's Disease.
Time Frame	At 24 and 64 weeks
Safety Issue	No

Population Description

Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups

	Description
Growth Hormone Plus Corticosteroid (CTX)	Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Corticosteroid (CTX)	Subjects took corticosteroid as prescribed by their physician

Measured Values

	Growth Hormone Plus Corticosteroid (CTX)	Corticosteroid (CTX)
Number of Participants Analyzed [units: participants]	10	10
Fecal Calprotectin [units: micrograms per gram (microg/g)] Mean ( 95% Confidence Interval )
Baseline	863 ( 517 to 1209 )	904 ( 540 to 1269 )
Week 12	868 ( 523 to 1214 )	656 ( 310 to 1002 )

No statistical analysis provided for Fecal Calprotectin

8. Secondary:

Total Corticosteroid Use [ Time Frame: 12 weeks, 24 weeks ]

Results not yet posted. Anticipated Posting Date: No text entered. Safety Issue: No

Serious Adverse Events

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Other Adverse Events

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More Information

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Certain Agreements:

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.

Results Point of Contact:

Name/Title: Lee A. Denson
Organization: Cincinnati Children's Hospital Medical Center
phone: 513-636-7575
e-mail: lee.denson@cchmc.org

No publications provided

Responsible Party:	Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:	NCT00109473 History of Changes
Other Study ID Numbers:	CCHMC IRB #: 04-12-06, IND # 71,344
Study First Received:	April 28, 2005
Results First Received:	June 24, 2011
Last Updated:	October 10, 2011
Health Authority:	United States: Food and Drug Administration

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