A Phase II, Randomized Controlled Trial of Recombinant Human Growth Hormone During Rehabilitation From Traumatic Brain Injury.
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 63
- 试验地点
- 3
- 主要终点
- Functional Outcome 6 Months After Injury, as Measured by the Processing Speed Index
研究概览
简要总结
Growth Hormone (GH) deficiency, defined by insufficient GH response to a variety of stimulating compounds, is found in 20-35% of adults who suffer traumatic brain injuries (TBI) requiring inpatient rehabilitation1. However, there is no accepted gold standard for diagnosing GH deficiency in this population. Further, the major effector molecule of the somatotropic axis, Insulin-Like Growth Factor-1 (IGF-1) has recently been recognized as an important neurotrophic agent. Since most repair and regeneration after TBI occurs within the first few months after injury, absolute or relative deficiencies of GH and IGF-1 in the subacute period after TBI are potentially important factors why some patients fail to make a good functional recovery. The proposed study is a randomized, double-blind, placebo-controlled trial of rhGH, starting at 1 month post TBI, continuing for 6 months.
This study has one primary hypothesis, that treatment with recombinant human Growth Hormone (rhGH) in the subacute period after TBI results in improved functional outcome 6 months after injury. As secondary hypotheses, we will investigate what is the optimal method to diagnose GH deficiency in TBI survivors and study the relationship between GH deficiency and insufficiency and functional recovery.
详细描述
- Patient selection and enrollment. Participants will be recruited into the study from subjects admitted for acute inpatient rehabilitation in the North Texas Traumatic Brain Injury Model Systems (NT-TBIMS) affiliated rehabilitation units. Our goal is to enroll participants who have the potential for neuroregeneration, but who suffered a sufficiently severe injury that the chance of full recovery (to normal pre-injury function) is low. Over a 4 year enrollment period, we plan to randomize 168 subjects into the study (with the anticipation that 71 will complete each arm of the trial).
Inclusion Criteria
-
Non-penetrating TBI
-
Age 18 - 50 years.
-
Admission to a North Texas Traumatic Brain Injury Model System-affiliated rehabilitation unit within 8 weeks of injury. Enrollment in TBI-MS database not required.
-
Randomization within 2 - 10 weeks of injury.
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Rancho Los Amigos Rating IV or better at the time of randomization. Should not be at Rancho IV level for more than 4 weeks before randomization.
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GH deficiency diagnosed by either of the following two criteria:
-
. Peak GH response to L-arginine stimulation test < 1.4 microg/L; or
-
. Plasma IGF-1 level 1 SD below the expected median for age and body weight. 6. Availability of caregiver to oversee administration of medications. 7. Reasonable expectation for completion of outcome measures 8. Residence inside the United States.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Non-penetrating TBI
- •Age 18 - 50 years.
- •Admission to a North Texas Traumatic Brain Injury Model System-affiliated rehabilitation unit within 8 weeks of injury. Enrollment in TBI-MS database not required.
- •Randomization within 2 - 10 weeks of injury.
- •Rancho Los Amigos Rating IV or better at the time of randomization. Should not be at Rancho IV level for more than 4 weeks before randomization.
- •GH deficiency diagnosed by either of the following two criteria:
- •. Peak GH response to L-arginine stimulation test < 1.4 microg/L; or
- •. Plasma IGF-1 level 1 SD below the expected median for age and body weight.
- •Availability of caregiver to oversee administration of medications.
- •Reasonable expectation for completion of outcome measures
- •Residence inside the United States
排除标准
- •History of pre-existing neurologic disease (such as epilepsy, brain tumors, meningitis, cerebral palsy, encephalitis, brain abscesses, vascular malformations, cerebrovascular disease, Alzheimer's disease, multiple sclerosis, or HIV-encephalitis)
- •History of premorbid disabling condition that interfere with outcome assessments
- •Contraindication to rhGH therapy. (hypersensitivity to rhGH or any of the components of the supplied product, including metacresol, glycerin, or benzyl alcohol)
- •Penetrating traumatic brain injury
- •Diabetes mellitus.
- •Obesity (BMI > 30).
- •Active infection.
- •Active malignant disease.
- •Acute critical illness, heart failure, or acute respiratory failure
- •Previous hospitalization for TBI > 1 day
- •Membership in a vulnerable population (prisoner)
- •Pregnancy. Women of childbearing age will be given a pregnancy test during screening to exclude pregnancy.
- •Lactating females
研究组 & 干预措施
1
The GH treatment arm will receive a starting dose of 400 microgramsg/day, with increases (or decreases) in dose by 100-200 micrograms/day each month, monitoring for side effects, until goal IGF-1 (in the upper quartile of the range for age and body weight) is reached up to maximum dose of 1,000 microgramsg/day. Dose adjustments may be modified by the investigators for participants receiving oral estrogens or other circumstances know to influence GH dosing or atypical responses to treatment.
干预措施: Recombinant human Growth Hormone (Drug)
2
Doses for participants receiving placebo will also be adjusted monthly to maintain the blinding.
干预措施: Placebo (Drug)
结局指标
主要结局
Functional Outcome 6 Months After Injury, as Measured by the Processing Speed Index
时间窗: 6 months
Processing Speed Index ages standardized score. In this scale, higher scores represent better functioning, lower scores represent poorer function. 100 = mean of a normative population. 110 = 1 standard deviation above normal; 90 = 1 standard deviation below normal 120 = 2 standard deviations above normal; 80 = 2 standard deviations below normal
次要结局
- IGF-1 Levels.(4 years)
- IGF-1 Levels(Baseline)
- Rates of Diabetes Mellitus, Arthralgias, or Peripheral Edema.(4 years)
- Processing Speed Index 1 Year After Injury(1 year)
- GH Response to L-arginine Stimulation at Baseline(1 day)
研究者
Ramon Diaz-Arrastia
Professor of Neurology
University of Pennsylvania