MAINTENANCE: Individualizing Dose of Growth Hormone to Maintain Normal Growth Velocity After Fulfilled Catch up Growth in Children

• Sponsor: Göteborg University (Other)
• Overall Status: Completed
• CT.gov ID: NCT02879747
• Collaborator: Pfizer (Industry)
• Enrollment: 99
• Arms: 2
• Actual Duration (Months): 168

Study Details

Study Description

Brief Summary

The objective was to study whether normal growth velocity can be maintained with adapted GH dosage in GH treated prepubertal children who have responded to GH treatment with fulfilled catch up growth (=difference to target height reached, less than - 0.6 SDS).

Condition or Disease	Intervention/Treatment	Phase
Short Stature	Drug: Genotropin	Phase 2/Phase 3

Detailed Description

The aim of the trial is to study the effect of adapted GH treatment in order to find an individualized GH dose maintaining normal growth velocity close to target height SDS and normal metabolism after fulfilled catch up growth in prepubertal children treated with individual doses of GH within the trial 98-0198-003 (1). The overall aim is to find for the individual the lowest effective GH dose during maintenance period, maintaining normal growth velocity and metabolism, i.e. a satisfactory biological active dose.

Study Design

• Study Type: Interventional
• Actual Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Individualizing the Dose of Growth Hormone (GH) to Maintain Normal Growth Velocity After Fulfilled Catch up Growth in Children Within TR 98-0198-003
• Actual Study Start Date: Dec 1, 2003
• Actual Primary Completion Date: Mar 1, 2012
• Actual Study Completion Date: Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Interventional Unchanged dose Genotropin	Drug: Genotropin; Children were randomized to either decreased dose by 50% or unchanged dose after 2-3 years of Catch-up growth
Active Comparator: Interventional 2 reduced dose 50% Genotropin	Drug: Genotropin; Children were randomized to either decreased dose by 50% or unchanged dose after 2-3 years of Catch-up growth

Outcome Measures

Primary Outcome Measures

1. The Proportion of Children Maintaining Normal Growth Velocity [twelve months]

   The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose)

Secondary Outcome Measures

1. IGF-I [start of study to two years after start in the trial]

   Delta Insulin-like growth factor-I (24 months after start compared to start of study) expressed as ng/ml and converted to standard deviation scores (SDS) to adjust for gender and age. A standard deviation score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A mean value within +-0.5 SDS and a range within +-1.0 SDS is a favorable outcome.

2. Height SDS at Start of Puberty [1-7 years in the trial]

   Height at start of puberty measured as cm and expressed as standard deviation score (SDS) to adjust for age and gender

Other Outcome Measures

1. Changes in Height [start of study to two years after start in the trial]

   Changes in height standard deviation scores (SDS) (calculated as height in cm at start converted to SDS and height in cm after two years in the trial converted to SDS)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 4 Years to 18 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Participated in the 'GH-dose catch-up study' 98- 0198-003.

• Midparental height reached (difference less than 0.6 SDS)

• Prepubertal at start of the study (girls =B 1, boys: testes :<; 3ml).

• Signed written informed consent from the patient's parents (and the child if old enough)

Exclusion Criteria:

• Disease affecting growth other than correctly treated hypothyroidism.

• Incapable of following the study protocol (i.e. bad compliance in the previous study).

• Puberty (> breast stage 2, or testes > 4ml).

• Poor compliance.

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

• Göteborg University
• Pfizer

Investigators

• Principal Investigator: Berit Kriström, MD, Umeå University Hospital
• Principal Investigator: Nils-Östen Nilsson, MD, Halmstad Department of Pediatrics
• Principal Investigator: Maria Halldin, MD, Uppsala University Hospital
• Principal Investigator: Sten Ivarsson, MD, Prof, Malmö Academic Hospital
• Principal Investigator: Kerstin Albertsson-Wikland, MD, prof, Gothenburg University, Departments of pediatrics

Study Documents (Full-Text)

None provided.

More Information

Publications

• Wikland KA, Kriström B, Rosberg S, Svensson B, Nierop AF. Validated multivariate models predicting the growth response to GH treatment in individual short children with a broad range in GH secretion capacities. Pediatr Res. 2000 Oct;48(4):475-84.

• Responsible Party: Göteborg University
• ClinicalTrials.gov Identifier: NCT02879747
• Other Study ID Numbers: NRA 6280003
• First Posted: Aug 26, 2016
• Last Update Posted: Apr 30, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Göteborg University: treatment; growth hormone; childhood; short stature
• Additional relevant MeSH terms: Dwarfism

Study Results

Participant Flow

Recruitment Details	All children in the fix dose group and children in the individualized dose group who have reached their midparental height SDS (>- 0.6 SDS) during at least two years of GH-treatment within the 'GH-dose-catch up' study (TR 98-0198-003) and still are prepubertal were eligible in the study.
Pre-assignment Detail	If glucose levels at the day of inclusion were higher than 7.1 mmol/L, then the child was excluded before assignment.

Arm/Group Title	Decreased GH Dose	Unchanged GH Dose	Control Group
Arm/Group Description	Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group with informed consent but not randomized
Period Title: Overall Study
STARTED	27	38	33
COMPLETED	23	32	31
NOT COMPLETED	4	6	2

Baseline Characteristics

Arm/Group Title	Decreased GH Dose	Unchanged GH Dose	Control Group	Total
Arm/Group Description	Reduced dose 50% Genotropin Genotropin: Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Unchanged dose Genotropin Genotropin: Children were randomized to unchanged GH dose after 2-3 years of Catch-up growth	Control Group randomized in the previous study to fix dose. This group of children continued with fix dose in the current trial after signing informed consent.	Total of all reporting groups
Overall Participants	27	38	33	98
Age (Count of Participants)
<=18 years	27 100%	38 100%	33 100%	98 100%
Between 18 and 65 years	0 0%	0 0%	0 0%	0 0%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	8.53 (1.51)	8.52 (2.11)	8.33 (1.78)	8.52 (1.99)
Sex: Female, Male (Count of Participants)
Female	7 25.9%	11 28.9%	8 24.2%	26 26.5%
Male	20 74.1%	27 71.1%	25 75.8%	72 73.5%
Region of Enrollment (participants) [Number]
Sweden	27 100%	38 100%	33 100%	65 66.3%

Outcome Measures

1. Primary Outcome

Title	The Proportion of Children Maintaining Normal Growth Velocity
Description	The proportion of children in the intervention 1 group (=reduced dose) that maintained an individual ΔheightSDS within ±0.3 during the first year of the Maintenance trial, compared to the proportion of children in the intervention 2 group (non-reduced dose)
Time Frame	twelve months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Decreased GH Dose	Interventional 2	Control Group
Arm/Group Description	Decreased GH dose Genotropin Genotropin: Children were randomized to 50% GH dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Unchanged GH dose Genotropin: Children were randomized to unchanged dose after 2-3 years of initial GH treatment in previous trial (years depending on achieved Catch-up)	Control Group children with fix dose through the previous and current trial and with signed consent
Measure Participants	27	38	33
Count of Participants [Participants]	23 85.2%	32 84.2%	31 93.9%

2. Secondary Outcome

Title	IGF-I
Description	Delta Insulin-like growth factor-I (24 months after start compared to start of study) expressed as ng/ml and converted to standard deviation scores (SDS) to adjust for gender and age. A standard deviation score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. A mean value within +-0.5 SDS and a range within +-1.0 SDS is a favorable outcome.
Time Frame	start of study to two years after start in the trial

Outcome Measure Data

Analysis Population Description

Drop outs due to puberty or adverse events

Arm/Group Title	Unchanged Dose	Reduced Dose	Control Group
Arm/Group Description	Unchanged dose Genotropin Genotropin: Children were randomized to unchanged GH dose after 2-3 years of Catch-up growth	reduced dose 50% Genotropin Genotropin: Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Control Group treated with fix dose GH according to previous and current trial, with signed informed consent
Measure Participants	15	22	23
Mean (Standard Deviation) [standard deviation scores]	-1.10 (1.14)	0.58 (0.91)	-0.06 (1.26)

3. Secondary Outcome

Title	Height SDS at Start of Puberty
Description	Height at start of puberty measured as cm and expressed as standard deviation score (SDS) to adjust for age and gender
Time Frame	1-7 years in the trial

Outcome Measure Data

Analysis Population Description

All 98 Children were measured at start of puberty

Arm/Group Title	Decreased GH Dose	Unchanged GH Dose	Control Group
Arm/Group Description	Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth	Children were randomized to unchanged GH dose after 2-3 years of Catch-up growth	Randomized in the previous study to fix dose. This Group of Children continued with fix dose in the current trial
Measure Participants	27	38	33
Mean (Standard Deviation) [standard deviation scores]	-1.0 (1.02)	-1.06 (0.84)	-0.98 (0.91)

4. Other Pre-specified Outcome

Title	Changes in Height
Description	Changes in height standard deviation scores (SDS) (calculated as height in cm at start converted to SDS and height in cm after two years in the trial converted to SDS)
Time Frame	start of study to two years after start in the trial

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Unchanged Dose	Reduced Dose	Control Group
Arm/Group Description	Unchanged dose Genotropin Genotropin: Children were randomized to either decreased dose by 50% or unchanged dose after 2-3 years of Catch-up growth	reduced dose 50% Genotropin Genotropin: Children were randomized to either decreased dose by 50% or unchanged dose after 2-3 years of Catch-up growth	Control Group with fix dose throughout the previous and current trial. Signed informed consent.
Measure Participants	15	22	23
Mean (Standard Deviation) [standard deviation scores]	0.18 (0.16)	0.57 (0.36)	0.55 (0.26)

Adverse Events

Time Frame	Two years or in some cases up to seven prepubertal years
Adverse Event Reporting Description	No relevant information according to reviewer.
Arm/Group Title	Decreased GH Dose		Unchanged GH Dose		Control Group
Arm/Group Description	Reduced dose 50% Genotropin Children were randomized to decreased GH dose by 50% after 2-3 years of Catch-up growth		Unchanged dose Children were randomized to unchanged dose after 2-3 years of Catch-up growth		Control Group with fix dose. Children that were randomized to fix dose in the previous and current trial and signed informed consent
All Cause Mortality
	Decreased GH Dose		Unchanged GH Dose		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/27 (0%)		0/38 (0%)		0/33 (0%)
Serious Adverse Events
	Decreased GH Dose		Unchanged GH Dose		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	3/27 (11.1%)		4/38 (10.5%)		3/33 (9.1%)
Ear and labyrinth disorders
Otitis media	1/27 (3.7%)	1	0/38 (0%)	0	0/33 (0%)	0
Gastrointestinal disorders
Abdominal pain	1/27 (3.7%)	1	1/38 (2.6%)	1	0/33 (0%)	0
Infections and infestations
facial nerve palsy due to tick disease	1/27 (3.7%)	1	0/38 (0%)	0	0/33 (0%)	0
Urinary tract infection (upper)	0/27 (0%)	0	0/38 (0%)	0	2/33 (6.1%)	2
Injury, poisoning and procedural complications
accident	0/27 (0%)	0	1/38 (2.6%)	1	0/33 (0%)	0
fracture	0/27 (0%)	0	2/38 (5.3%)	2	1/33 (3%)	1
Other (Not Including Serious) Adverse Events
	Decreased GH Dose		Unchanged GH Dose		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	20/27 (74.1%)		25/38 (65.8%)		24/33 (72.7%)
Infections and infestations
virosis	20/27 (74.1%)	52	25/38 (65.8%)	46	24/33 (72.7%)	53

Limitations/Caveats

[Not Specified]

More Information

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.