Brain Injuries, Growth Hormone Deficiency
Conditions
Keywords
traumatic brain Injury, cognitive function
Brief summary
To establish the effects of genotropin replacement on cognitive function in patients with severe growth hormone deficiency after traumatic brain injury.
Detailed description
The study was terminated on 15-Dec-2008 due to an inability to recruit the protocol specified patient population. The study has not been terminated due to any safety concerns.
Interventions
DRUGGenotropin
Subcutaneous injection, starting dose 0.2mg/day for males and 0.3mg/day for female with dose titration at 0.1mg to 0.2 mg increments in accordance to IGF-1 results for a total duration of 36 weeks.
DRUGPlacebo
Subcutaneous injection, with dummy dose titration for a total duration of 36 weeks.
Sponsors
Pfizer
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* Have had a previous traumatic brain injury (more than 1 year and less than 20 years) prior to the screening visit. * Have an Extended Glasgow Outcome Scale (GOS-E) more than or equal to 5. * Have proven GHD deficiency
Exclusion criteria
* Active systemic malignancy or active intracranial tumor. A successfully treated tumor or malignancy is not an exclusion criterion if the patient has not had active disease for 5 years and is not currently receiving maintenance chemotherapy, (except for basal cell skin cancers. * Receiving treatment with prednisolone in doses above 10 mg/day or treatment with other oral glucocorticosteroids above replacement doses is not permitted throughout the study. Topical and inhaled corticosteroids are permitted. * History of dementia unrelated to TBI * History of benign intracranial hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in the Cognitive Function (CogState™) Composite Score at Week 36 | Baseline, Week 36 | CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Lean Body Mass and Fat Mass at Week 36 | Baseline, Week 36 | The change from Baseline values for lean body mass and fat mass is calculated as the difference between the parameter values at Visit 36, and the parameter values at Baseline. |
| Change From Baseline in Neurological Outcome as Assessed by Extended Glasgow Outcome Scale (GOS-E) at Week 36 | Baseline, Week 36 | The GOS is widely used for assessing outcome after head injury and non-traumatic acute brain insults and is performed by a physician. The GOS-E uses eight points to assess disability and handicap. The GOS-E focuses on how the injury has affected functioning in major areas of life rather than on the particular deficits and symptoms caused by injury. The overall score ranges from 1-8; 1=Death and 8=Upper Good Recovery |
| Change From Baseline in Quality of Life Using Short Form (SF)-36 Health Survey at Week 36 | Baseline, Week 36 | A subject administered scale assessing general quality of life. A subject administered score, scale, direction of scale. The SF-36 consists of 36 questions covering the following eight health domains (subscales): Physical Functioning, Bodily Pain, Role Limitations Due to Physical Problems, Role Limitations Due to Emotional Problems, General Health Perceptions, Mental Health, Social Function, Vitality. |
| Change From Baseline in CogState™ at Week 12 and 24. | Baseline, Week 12 and 24 | CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance. |
| Change From Baseline in Cardiovascular Risk | Baseline, Weeks 2, 4, 12, 24, and 36 | The cardiovascular risk parameters (low-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, total cholesterol and fasting triglycerides) was measured at all visits (Weeks 2, 4, 12, 24, and 36). |
| Change From Baseline in Weight | Baseline, Weeks 2, 4, 12, 24, and 36 | — |
| Change From Baseline in Waist Circumference | Baseline, Weeks 2, 4, 12, 24, and 36 | — |
| Change From Baseline In Assessment of Growth Hormone Deficiency in Adults (AGHDA) Questionnaires at Week 36 | Baseline, Week 36 | The AGHDA is a quality of life subject-administered questionnaire that is condition-specific and comprises of 25 'Yes' or 'No' statements covering 6 dimensions - mobility, pain, energy, sleep, emotional reactions and social isolation. The AGHDA total score change from Baseline values is calculated as the difference between the total score at Visit 6 (Week 36), and the total score at Baseline. |
Countries
France, Italy, Netherlands, Spain, Sweden, United Kingdom
Participant flow
Recruitment details
Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Participants by arm
| Arm | Count |
|---|---|
| Genotropin Initiated at 0.2 mg/day subcutaneously (SC) in men and 0.3 mg/day SC in women. Dose adapted monthly in 0.1 or 0.2 mg increments until stabilized in upper half of normal range. | 4 |
| Placebo Matching placebo injected SC. | 6 |
| Total | 10 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Terminated by Sponsor | 2 | 5 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Genotropin | Placebo | Total |
|---|---|---|---|
| Age, Customized 18 - 44 years | 4 participants | 4 participants | 8 participants |
| Age, Customized <18 years | 0 participants | 0 participants | 0 participants |
| Age, Customized 45-64 years | 0 participants | 2 participants | 2 participants |
| Age, Customized >=65 years | 0 participants | 0 participants | 0 participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 4 Participants | 6 Participants | 10 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 4 / 4 | 0 / 6 |
| serious Total, serious adverse events | 0 / 4 | 0 / 6 |
Outcome results
Primary
Change From Baseline in the Cognitive Function (CogState™) Composite Score at Week 36
CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance.
Time frame: Baseline, Week 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Secondary
Change From Baseline In Assessment of Growth Hormone Deficiency in Adults (AGHDA) Questionnaires at Week 36
The AGHDA is a quality of life subject-administered questionnaire that is condition-specific and comprises of 25 'Yes' or 'No' statements covering 6 dimensions - mobility, pain, energy, sleep, emotional reactions and social isolation. The AGHDA total score change from Baseline values is calculated as the difference between the total score at Visit 6 (Week 36), and the total score at Baseline.
Time frame: Baseline, Week 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Secondary
Change From Baseline in Cardiovascular Risk
The cardiovascular risk parameters (low-density lipoprotein-cholesterol, high-density lipoprotein cholesterol, total cholesterol and fasting triglycerides) was measured at all visits (Weeks 2, 4, 12, 24, and 36).
Time frame: Baseline, Weeks 2, 4, 12, 24, and 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Unknown | Change From Baseline in Cardiovascular Risk | Week 2 | — scores on a scale |
| Unknown | Change From Baseline in Cardiovascular Risk | Week 4 | — scores on a scale |
| Unknown | Change From Baseline in Cardiovascular Risk | Week 12 | — scores on a scale |
| Unknown | Change From Baseline in Cardiovascular Risk | Week 24 | — scores on a scale |
| Unknown | Change From Baseline in Cardiovascular Risk | Week 36 | — scores on a scale |
Secondary
Change From Baseline in CogState™ at Week 12 and 24.
CogState™: 7 tasks: Detection (Part A); Identification; One back working memory; Monitoring; One card learning; Prediction; Detection (Part B). Detection, Identification, Monitoring score range: 2 (worse) to 5 (best); One back working memory/one card learning score range: 0 (worse) to 1.57 (best); Prediction score range: 0 (worse) to 100 (best). Composite change score=average of cognitive change scores for each task at each postdrug assessment; total possible score: -300 to 300. Change=change from baseline (average of 2 postdose assessments). Positive composite score=improved performance.
Time frame: Baseline, Week 12 and 24
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Unknown | Change From Baseline in CogState™ at Week 12 and 24. | Week 12 | — scores on a scale |
| Unknown | Change From Baseline in CogState™ at Week 12 and 24. | Week 24 | — scores on a scale |
Secondary
Change From Baseline in Lean Body Mass and Fat Mass at Week 36
The change from Baseline values for lean body mass and fat mass is calculated as the difference between the parameter values at Visit 36, and the parameter values at Baseline.
Time frame: Baseline, Week 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Secondary
Change From Baseline in Neurological Outcome as Assessed by Extended Glasgow Outcome Scale (GOS-E) at Week 36
The GOS is widely used for assessing outcome after head injury and non-traumatic acute brain insults and is performed by a physician. The GOS-E uses eight points to assess disability and handicap. The GOS-E focuses on how the injury has affected functioning in major areas of life rather than on the particular deficits and symptoms caused by injury. The overall score ranges from 1-8; 1=Death and 8=Upper Good Recovery
Time frame: Baseline, Week 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Secondary
Change From Baseline in Quality of Life Using Short Form (SF)-36 Health Survey at Week 36
A subject administered scale assessing general quality of life. A subject administered score, scale, direction of scale. The SF-36 consists of 36 questions covering the following eight health domains (subscales): Physical Functioning, Bodily Pain, Role Limitations Due to Physical Problems, Role Limitations Due to Emotional Problems, General Health Perceptions, Mental Health, Social Function, Vitality.
Time frame: Baseline, Week 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
Secondary
Change From Baseline in Waist Circumference
Time frame: Baseline, Weeks 2, 4, 12, 24, and 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Unknown | Change From Baseline in Waist Circumference | Week 2 | — cm |
| Unknown | Change From Baseline in Waist Circumference | Week 4 | — cm |
| Unknown | Change From Baseline in Waist Circumference | Week 12 | — cm |
| Unknown | Change From Baseline in Waist Circumference | Week 24 | — cm |
| Unknown | Change From Baseline in Waist Circumference | Week 36 | — cm |
Secondary
Change From Baseline in Weight
Time frame: Baseline, Weeks 2, 4, 12, 24, and 36
Population: Due to poor recruitment, the study was terminated early; therefore efficacy analyses were not completed.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Unknown | Change From Baseline in Weight | Week 2 | — kg |
| Unknown | Change From Baseline in Weight | Week 4 | — kg |
| Unknown | Change From Baseline in Weight | Week 12 | — kg |
| Unknown | Change From Baseline in Weight | Week 24 | — kg |
| Unknown | Change From Baseline in Weight | Week 36 | — kg |