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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.
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  
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 
Overall Participants Analyzed 
[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) 
[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.
IGF-I Standard Deviations Score (SDS) [1] 
[Units: Standard deviation scores]
Mean (Standard Deviation)
 -2.72  (2.23)   -2.82  (1.97)   -2.39  (2.03)   -2.73  (2.19) 
[1] 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.
Maximum Growth Hormone (GH) Peak on Stimulation Test [1] 
[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) 
[1] 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.
Body Mass Index (BMI) [1] 
[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) 
[1] 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.
Diagnosis Leading to GHD [1] 
[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 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


Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Responsible Party: Eli Lilly and Company
ClinicalTrials.gov Identifier: NCT01088399     History of Changes
Other Study ID Numbers: 6448
B9R-MC-GDGA ( Other Identifier: Eli Lilly and Company )
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