Dubiel et al. (2018)

United States

RCT

PEDro=7

N=40

Population: Mean age=31.1yr; Gender: Male=34, Female=6; Mean Time Post-injury=64.1d. GCS: mild=4, Moderate=3, Severe=32, unknown=1.

Intervention: Individuals were randomized to receive either recombinant human growth hormone or placebo. Follow-up was at 1-mo, 3-mo, 6-mo and 12-mo. 1-mo and 3-mo follow-up was only taken for IGF-1 concentrations.

Outcome Measure: Disability rating scale scores (DRS), Functional Independence Measure (FIM) motor, FIM Cognitive, FIM total, IGF-1, Peak L-Arginine, California Verbal Learning Test (CVLT), Trail making test-A, Trail Making test-B.

1.        At 3-mo and 6-mo follow-up the rhGH group had significantly higher IGF-1 concentrations (p=0.035, p=0.005), these were not observed at 1-mo or 12-mo follow-up.

2.        At 6-mo follow-up the rhGH group had a significantly higher positive change in FIM motor scores (p=0.02), FIM cognitive scores (p=0.02), and total change in FIM scores (p=0.02). There were no other significant differences at 6-mo.

3.        At 12-mo follow-up the rhGH group had maintained significantly higher positive scores in FIM motor scores (p=0.02), and total FIM change (p=0.01). There were no other significant differences at 12-mo follow-up.

High Jr et al. (2010)

USA

RCT

PEDro=8

N=23

Population: TBI. Placebo (n=11): Mean Age=39.1 yr; Time Post Injury=5.1 yr.Active rhGH (n=12): Mean Age=36.1 yr; Time Post Injury=11 yr.

Intervention: Participants were randomized to either a growth hormone replacement injection (rhGH) group or a placebo injection. Initially the drug was administered at 200 ug, followed by a 200 ug increase every month until the dosage reached 600 ug. Both groups received these injections for one year.

Outcome Measure: Wechsler Adult Intelligence Scale-III, Delis-Kaplan Executive Function System.

1.        Overall study results did not show great improvements on the majority of assessments between groups.

2.        There was a significant improvement on the Finger tapping demonstrated in the treatment group.

3.        Processing Speed Index: the treatment group improved significantly over the one-year period (p<0.050). The control group showed improvement at the end of the first 6 mo (p<0.010) but this was not seen at the end of the 1 yr.

4.        Significant improvement was also noted on the Wisconsin Card Sorting Test (executive functioning) for the treatment group (p<0.010).

Hatton et al. (1997)

USA

RCT

PEDro=5

N=33

Population: TBI; Intervention Group (n=17): Mean Age=27.6yr; Gender: Male=14, Female=3; Mean GCS=7; Mean Time Post Injury=56.5hr; Control Group (n=16): Mean Age=27.8yr; Gender: Males=14, Females=2; Mean GCS=6.1; Mean Time Post Injury=57.1 hr.

Intervention: Patients were randomly allocated to receive either continuous IV IGF-1 (0.01mg/kg/hr, treatment) or no IV treatment (control). IGF-I treatment began within 72hr of injury and continued for up to 14d. Both groups received nutritional support and neurosurgical intensive care. Patient assessments were made on 15d, 30d, discharge, and 3 and 6mo follow-up.

Outcome Measure: Glasgow Outcome Scale (Klionsky et al.), Weight Loss, Glucose Concentrations, Nitrogen Balance.

1.        IGF-1 treatment resulted in lower daily glucose concentration and nitrogen output (p=0.03) when compared to placebo.

2.        Patients receiving IGF-1 treatment showed weight gain while those receiving placebo showed significant weight loss (p=0.02).

3.        In patients with GCS=5-7, those receiving IGF-1 showed better outcome on GOS than those receiving placebo (p=0.06).

Mossberg et al. (2017) United States Pre-Post N=15

Population: TBI=15: Mean Age=45.5yr; Gender: Males=10, Females=5; Mean Time Post-Injury=11.2yr.

Intervention: Daily injections of recombinant human growth hormone (rhGH) for 12 mo.

Outcome Measure: Cardiorespiratory symptoms, Muscle force testing, Body composition, Cognitive function (BDI, Fatigue Severity Scale (FSS)).

1.        There were no significant differences between pre and post measures of cardiorespiration (oxygen uptake, heart rate, minute ventilation, respiratory exchange ratio, oxygen pulse).

2.        Although skeletal muscle fatigue did not decrease over the course of treatment, there was a strong trend for a decrease in perceived fatigue (p=0.06).

3.        There was a strong trend for an increase in lean mass (p=0.06) post-treatment.

4.        There was a significant improvement in both BDI (p=0.019) and FSS (p=0.039) scores post-treatment.

Gardner et al. (2015)

Sweden

Case Control

N=1429

Population: TBI (n=161): Mean Age=42.6yr; Gender: Male=93, Female=68. Tumour (n=1268): Mean Age=53.2yr; Gender: Male=786, Female=482.

Intervention: Participants diagnosed with GHD and treated with GH therapy were included in retrospective analysis.

Outcome Measures: Quality of Life Assessment of GHD in Adults (QOL-AGHDA).

1.        At baseline, mean QOL-AGHDA scores were significantly worse in the TBI group than in the Tumour group (p<0.0001).

2.        After 1yr of treatment, mean improvement in QOL-AGHDA was greater in the TBI group than in the Tumour group (p=0.04), but the score remained worse in the TBI group.

3.        Over 8 yr of treatment, mean improvement in QOL-AGHDA was maintained in both groups, but the score remained worse in the TBI group.

Devesa et al. (2013)

Spain

Pre-Post N=12

Population: TBI; Mean Age=28.4yr; Gender: Male=8, Female=4; Mean Time Post Injury=5.3yr.

Intervention: Participants received GH therapy (1mg/d, 5d/wk, 8mo) and clinical rehabilitation (3-4hr/d, 5d/wk, 6-12mo). Diagnosis of GHD was made by the following criteria: plasma GH <7ng/mL.

Outcome Measures: Plasma IGF-1.

1.        GHD was diagnosed in 42% of participants.

2.        Before treatment, mean plasma IGF-1 levels were significantly lower in the GHD group than in the non-GHD group (p<0.05).

3.        After treatment, mean plasma IGF-1 levels significantly increased in both the GHD group (p<0.01) and non-GHD group (p<0.05), such that the two groups were no longer significantly different (p>0.05).

4.        Percentage increase in IFG-1 levels was significantly higher in the GHD group than in the non-GHD group (p<0.01).

Moreau et al. (2013b)

France

PCT

N=50

Population:  TBI. Treatment Group (TG, n=23): Mean Age=37.9 yr; Gender: Male=19, Female=4; Mean Time Post Injury=7.8 yr; Mean GCS=8.1. Control Group (CG, n=27): Mean Age=37.1 yr; Gender: Male=24, Female=3; Mean Time Post Injury=5.5 yr; Mean GCS=9.4.

Intervention: Participants were allocated to receive GH therapy (TG, 0.2-0.6mg/d) or no treatment (CG) for 1yr. Outcomes were assessed before (T1) and after (T2) treatment.

Outcome Measures: Activities of Daily Living (ADL); Quality of Life Brain Injury (QOLBI); Verbal Memory (VM); Rey Complex Figure (RCF); Reaction Time (RT).

1.        Both groups showed significant improvement in instrumental ADL (iADL, p=0.001) at T2, but not personal ADL (pADL).

2.        Both groups showed significant improvement in QOLBI total scores (p=0.019) and intellectual (p=0.001), functional (p=0.023), and personal (p=0.044) subscores at T2, but not physical, psychological, and social subscores.

3.        Both groups showed significant improvement (p<0.050) in aspects of attention (RT), memory (VM), and visuospatial (RCF) abilities at T2.

4.        The TG showed significantly greater improvement in QOLBI functional (p=0.023) and personal (p=0.019) subscores, as well as RCF (p=0.037), but no significant difference was found for other outcome measures.

5.        There was a significant correlation (p<0.050) between QOLBI total and pADL (r=0.49).

6.        There was a significant negative correlation (p<0.01) between attention (RT) and pADL (r=-0.59) and iADL (r=-0.56).

Reimunde et al. (2011)

Spain

Cohort

N=19

Population: TBI; Gender: Male=19, Female=0. With Growth Hormone Deficiency (GHD) Group (n=11): Mean Age=53.36 yr; Mean Time Post Injury=44.55 mo. Without GHD group (n=8): Mean Age=47.12 yr; Mean Time Post Injury=46.6 mo.

Intervention: Those with GHD received recombinant human GH (rhGH), subcutaneously (0.5 mg/d for 20d then 1 mg/d for 5 d). Those without GHD were given a placebo. Cognitive rehabilitation was given to everyone (1 hr/d, 5d for 3 mo).

Outcome Measure: Weschler Adult Intelligence Scale (WAIS).

1.        Results of the WAIS indicated that the control group improved significantly on the digits and manipulative intelligence quotient (p<0.050).

2.        For those in the treatment groups improvement was noted in cognitive parameters: understanding digits, numbers and incomplete figures (p<0.050) and similarities vocabulary, verbal IQ, Manipulative IQ, and total IQ (p<0.010).