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A Prospective Observational Study of Effect of Somatropin on Growth Hormone Deficient Adults (HypoCCS)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Eli Lilly and Company
ClinicalTrials.gov Identifier:
NCT01088399
First received: February 25, 2010
Last updated: March 25, 2014
Last verified: March 2014
Results First Received: January 13, 2014  
Study Type: Observational
Study Design: Observational Model: Cohort;   Time Perspective: Prospective
Conditions: Hypopituitarism
Pituitary Insufficiency
Growth Hormone Deficiency, Adult
Intervention: Drug: Somatropin (rDNA origin)

  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
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
Participants were initially enrolled in 2 regional observational studies (B9R-EW-GDDQ [GDDQ] initiated in 1997 and B9R-MC-GDEE [GDEE] in 1998) which were merged into the global Study B9R-MC-GDGA (GDGA, NCT01088399) in 2002. This record spans approximately 15 years from the initial enrollment in regional studies to completion of Study GDGA.

Reporting Groups
  Description
Somatropin Treated Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants.
Untreated Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
Unknown It is not known whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.

Participant Flow:   Overall Study
    Somatropin Treated     Untreated     Unknown  
STARTED     8716     1655     302  
COMPLETED     1595     308     21  
NOT COMPLETED     7121     1347     281  
Adverse Event                 211                 16                 0  
Death                 204                 45                 0  
Lack of Efficacy                 298                 7                 5  
Lost to Follow-up                 1070                 278                 58  
Physician Decision                 531                 88                 16  
Withdrawal by Subject                 544                 195                 33  
Change to or start of somatropin therapy                 234                 17                 12  
Sponsor decision                 1573                 298                 7  
Protocol Violation                 10                 1                 0  
Enrollment criteria not met                 48                 119                 70  
Study summary visit not completed                 2398                 283                 80  



  Baseline Characteristics
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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
Somatropin Treated Participants received somatropin therapy dosed according to the local product label during the study. No form of intervention was imposed on the participants.
Untreated Participants did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
Unknown It is unknown whether participants did or did not receive somatropin therapy during the study. No form of intervention was imposed on the participants.
Total Total of all reporting groups

Baseline Measures
    Somatropin Treated     Untreated     Unknown     Total  
Number of Participants  
[units: participants]
  8716     1655     302     10673  
Age, Customized  
[units: participants]
       
<20 years     421     36     10     467  
20 years to <30 years     1258     152     36     1446  
30 years to <40 years     1475     173     54     1702  
40 years to <50 years     1975     318     76     2369  
50 years to <60 years     2048     379     74     2501  
60 years to <70 years     1116     324     38     1478  
>=70 years     421     272     13     706  
unknown     2     1     1     4  
Gender  
[units: participants]
       
Female     4158     714     155     5027  
Male     4558     941     147     5646  
Race/Ethnicity, Customized  
[units: participants]
       
African Descent     226     96     14     336  
Caucasian     6058     1080     236     7374  
East/Southeast Asian     460     129     7     596  
Hispanic     153     55     16     224  
Western Asian     24     5     3     32  
Other     38     10     2     50  
Declined To Provide     387     82     12     481  
Unknown     1370     198     12     1580  
Region of Enrollment  
[units: participants]
       
Austria     77     1     1     79  
Belgium     55     1     0     56  
Canada     63     51     0     114  
Czech Republic     77     5     0     82  
Denmark     151     5     0     156  
France     452     218     6     676  
Germany     553     87     19     659  
Hungary     102     2     0     104  
Iceland     10     1     1     12  
Italy     1242     64     49     1355  
Japan     407     102     0     509  
Norway     17     0     0     17  
Spain     427     55     2     484  
Sweden     355     3     2     360  
Netherlands     460     1     0     461  
United Kingdom     538     15     6     559  
United States     3730     1044     216     4990  
Growth Hormone Deficiency (GHD) Onset Type  
[units: participants]
       
Adult     6968     1422     247     8637  
Childhood     1702     194     29     1925  
Unknown     46     39     26     111  
Insulin-like Growth Factor-I (IGF-I) [1]
[units: micrograms per liter (mcg/L)]
Mean ± Standard Deviation
  100.4  ± 78.0     75.0  ± 55.3     95.5  ± 63.7     96.4  ± 75.2  
IGF-I Standard Deviations Score (SDS) [2]
[units: standard deviation scores]
Mean ± Standard Deviation
  -2.72  ± 2.23     -2.82  ± 1.97     -2.39  ± 2.03     -2.73  ± 2.19  
Maximum Growth Hormone (GH) Peak on Stimulation Test [3]
[units: nanograms per milliliter (ng/mL)]
Mean ± Standard Deviation
       
GHRH + Arginine (Arg, n=1175, 103, 51, 1329)     2.5  ± 3.5     5.2  ± 8.1     4.4  ± 8.1     2.8  ± 4.4  
Any test except GHRH + Arg (n=6579;1178;168;7925)     1.1  ± 1.9     2.0  ± 3.7     5.2  ± 6.7     1.3  ± 2.5  
Body Mass Index (BMI) [4]
[units: kilograms per square meter (kg/m^2)]
Mean ± Standard Deviation
  29.7  ± 7.0     29.9  ± 7.0     30.0  ± 6.9     29.7  ± 7.0  
Diagnosis Leading to GHD [5]
[units: participants]
       
Pituitary adenoma     3769     865     79     4713  
Craniopharyngioma     973     125     24     1122  
Other Tumor     653     137     7     797  
Idiopathic     1381     177     88     1646  
Pituitary hemorrhage/brain injury     455     59     4     518  
Other less common specified diagnoses     1027     198     79     1304  
Causes other than listed above     458     94     21     573  
[1] Participants with available IGF-I data at baseline (n=5531, 1009, 194 with 6734 total participants). IGF-I is primary mediator of growth hormone (GH) and is used to monitor GH effectiveness, treatment adherence and IGF-I excess.
[2] Participants with available IGF-I SDS data at baseline (n=3743, 645, 113 with 4501 total participants). IGF-I is primary mediator of growth hormone (GH) and is used to monitor GH effectiveness, treatment adherence and IGF-I excess. As endogenous levels of GH, thereby IGF-I, decline throughout adulthood values are converted to age and gender adjusted standard deviation scores (SDS) based on general population normal data. The SDS is the number of standard deviations a subjects IGF-I concentration is different from the general population mean, either positive or negative.
[3] Participants with available maximum GH peak data at baseline (N=1175, 103, 51 with 1329 total participants analyzed). Maximum GH peak levels in response to medication (such as insulin or growth hormone releasing hormone (GHRH) plus arginine) or other intervention (such as exercise) was used to measure the ability of the pituitary gland to release GH and to diagnose and determine severity of GH deficiency. Severe GH deficiency in adults is a peak GH response of <3 milligrams/liter in response to an insulin tolerance test and is an accepted criterion for GH replacement therapy in adults.
[4] Participants with available BMI data at baseline (n=8263, 1452, 268, with 9983 total participants). Body mass index (BMI) is an estimate of body fat based on body weight divided by height squared.
[5] Participants with available diagnosis designation at baseline (n=8670, 1616, 276, with 10562 total participants). Other less common specified diagnoses contains participants who had histories including cranial irradiation, empty sella, hypophysitis, congenital defect resulting in GHD.



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Clinically Significant Adverse Events   [ Time Frame: Baseline to study completion (approximately 10 years) ]

2.  Secondary:   Cardiovascular Risk Factor-Change From Baseline in Body Mass Index (BMI)   [ Time Frame: Baseline, interim time point (5 years), and study completion (10 years) ]

3.  Secondary:   Cardiovascular Risk Factor-Change From Baseline in Systolic (SBP) and Diastolic Blood Pressure (DBP)   [ Time Frame: Baseline, interim time point (5 years), and study completion (10 years) ]

4.  Secondary:   Cardiovascular Risk Factor-Change From Baseline in Cholesterol and Triglycerides   [ Time Frame: Baseline, interim time point (5 years), and study completion (10 years) ]

5.  Secondary:   Cardiovascular Risk Factor-Change From Baseline in Waist Circumference   [ Time Frame: Baseline, interim time point (5 years), and study completion (10 years) ]

6.  Secondary:   Percentage of Participants Experiencing a Bone Fracture (Fracture Incidence)   [ Time Frame: Baseline through 10 years ]

7.  Secondary:   Change From Baseline in the Total Z Score of the Disease-specific Module of the Questions of Life Satisfaction (QLS-H).   [ Time Frame: Baseline, interim time point (5 years), and study completion (10 years) ]

8.  Other Pre-specified:   Number of Participants Who Died While in the Study   [ Time Frame: Study enrollment up to approximately 10 years ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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
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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 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked Other disclosure agreement that restricts the right of the PI to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Chief Medical Officer
Organization: Eli Lilly and Company
phone: 800-545-5979


No publications provided by Eli Lilly and Company

Publications automatically indexed to this study:

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01088399     History of Changes
Other Study ID Numbers: 6448, B9R-MC-GDGA
Study First Received: February 25, 2010
Results First Received: January 13, 2014
Last Updated: March 25, 2014
Health Authority: Austria: Ethikkommission
Belgium: Institutional Review Board
Canada: Ethics Review Committee
Czech Republic: Ethics Committee
France: French Data Protection Authority
France: Haute Autorité de Santé Transparency Commission
Germany: Ethics Commission
Germany: Federal Institute for Drugs and Medical Devices
Hungary: National Institute of Pharmacy
Hungary: Research Ethics Medical Committee
Italy: Ethics Committee
Japan: Institutional Review Board
Japan: Ministry of Health, Labor and Welfare
Netherlands: Independent Ethics Committee
Spain: Ministry of Health
Spain: Ethics Committee
Sweden: Regional Ethical Review Board
Sweden: Medical Products Agency
United Kingdom: Research Ethics Committee
United Kingdom: Medicines and Healthcare Products Regulatory Agency
United States: Institutional Review Board