Brain Injury, Endocrine Dysfunction, Trauma
Conditions
Keywords
Testosterone, Traumatic Brain Injury, Hypogonadism, Endocrine Dysfunction, Low Testosterone in men with new Traumatic Brain Injury
Brief summary
The purpose of this study was to address 3 short term objectives; (1) Determine the effects of physiologic testosterone (T) therapy on neurological function and functional independence following traumatic brain injury (TBI) in hypogonadal men during inpatient rehabilitation; (2) Document the natural history of neuroendocrine dysfunction and recovery in men during inpatient rehabilitation after TBI; (3) Obtain data to validate the NIH toolbox, a novel assessment of neurological function for use in the TBI population; and 2 long-term objectives: (1) Utilize study findings to design a multicenter trial to further assess the impact of T therapy in hypogonadal men following TBI and (2) Impact TBI practice management with new information about neuroendocrine dysfunction after TBI and hormone treatments to improve outcomes.
Detailed description
This randomized, double blind, placebo-controlled pilot study assessed the hormonal status of men on admission to an inpatient TBI rehabilitation program. 498 consecutively admitted men for TBI rehabilitation were screened for participation in the study. 22 participants with low T who met all criteria were randomized into placebo (n=10), or physiologic T therapy (n=12). Of those with normal T who met all criteria, 24 were randomized into a follow up group. All participants were evaluated every two weeks for up to 12 weeks: hormone levels, FIM ratings and NIH Toolbox testing as able. There was participant drop out over time as participants were discharged from the hospital. The final analysis examined differences between the normal T, low T Treatment and low T placebo groups on hormone levels, FIM ratings and NIH Toolbox results at baseline and weeks 2, 4 and 6.
Interventions
2.5 gram stickpacks administered with starting dosage of 5g increasing to a max of 10g.
OTHERPlacebo gel
2.5 gram stickpacks with starting dose of 5g increasing to max of 10g.
Sponsors
University of Colorado, Denver
Craig Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
16 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. History of TBI as defined as damage to brain tissue caused by an external mechanical force as evidenced by loss of consciousness or post traumatic amnesia (PTA) due to brain trauma or by objective neurological findings that can be reasonably attributed to TBI on physical examination or mental status examination;82 2. Moderate to severe TBI as indicated by a Glasgow Coma Scale (GCS) score of less than or equal to 12 at emergency department admission, or post traumatic amnesia (PTA) of greater than or equal to seven days post-injury, or radiographic evidence of intracranial injury; 3. Continuously hospitalized from time of injury until admission for rehabilitation; 4. Enrolled in study within 6 months of TBI; 5. Receiving inpatient rehabilitation for TBI at Craig Hospital; 6. Males between the ages of 16 to 65 (inclusive); 7. Approval by attending physician; 8. Testosterone level below the assay normal range; 9. Consent to study participation
Exclusion criteria
10. History of any conditions that would prohibit testing contained in the NIH toolbox; 11. Non-English or non-Spanish speaking (to the extent that would limit the ability to complete study measures); 12. History of prior psychiatric illness requiring hospitalization; 13. Prior testosterone therapy; 14. History of or current or suspected hormonally dependent cancer , including carcinoma of the breast or prostate cancer; 15. Known hypersensitivity to any T gel ingredients including alcohol and soy products; 16. Hematocrit (HCT) greater than 55% (normal range in Colorado is up to 52) or transaminase elevation \>4x upper limit of the normal range. 17. Abnormal finding on digital rectal examination such as nodule, asymmetry, or induration (Does not include enlarged prostate or abnormal rectal tone) 18. PSA\>4.0 19. BMI \<16 or \>40kg/m2 20. History of untreated prolactinoma 21. History of severe heart failure or uncontrolled medical problem that would interfere with the participant's safety in the study as determined by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Restricted Functional Independence Measure (FIM) | Administered at baseline and every other week for up to 12 weeks with 7 total possible administrations. | The FIM is the most widely accepted functional assessment measure in use in the rehabilitation community in the US. It is an 18-item ordinal clinician rating scale that is useful for assessment of functional skills progress during inpatient rehabilitation. It measures levels of independent/dependent performance of 13 motor functions and 5 cognitive functions. By adding the points for each item, the possible total score ranges from 18 to 126, with higher numbers indicating better performance. A restricted FIM total score that eliminated the toileting, bladder management and bowel management items was computed and used in the final analysis with scores ranging from 14-105). The restricted FIM total score was used as the primary outcome measure. |
Countries
United States
Participant flow
Recruitment details
Male in-patients with TBI at Craig Hospital meeting study criteria were screened from November 1, 2010 through July 24, 2014:
Pre-assignment details
A total of 46 participants meeting all criteria were enrolled and randomized of which 22 had low testosterone levels, and 24 who had normal T were followed as controls. The total number who started and were followed was 46.
Participants by arm
| Arm | Count |
|---|---|
| Low T Intervention - Treatment Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to either a treatment or placebo group. They will participate in blood assays at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization. They will also be scored on the FIM (primary outcome measure) and the NIH Toolbox (Secondary Outcome Measure.
Androgel (Testosterone Gel): 2.5 gram stickpacks administered with starting dosage of 5g increasing to a max of 10g. | 12 |
| Low T Intervention - Placebo Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to either a treatment or placebo group. They will participate in blood assays at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization. They will also be scored on the FIM (primary outcome measure) and the NIH Toolbox (Secondary Outcome Measure.
Androgel Placebo: 2.5 gram stickpacks with starting dose of 5g increasing to max of 10g. | 10 |
| Normal T No Intervention - Followed A subset of men with TBI meeting study criteria with Normal Testosterone levels were assessed at all data collection time points. They will participate in blood assays at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization. They will also be scored on the FIM (primary outcome measure) and the NIH Toolbox (Secondary Outcome Measure. | 24 |
| Total | 46 |
Baseline characteristics
| Characteristic | Low T Intervention - Treatment | Low T Intervention - Placebo | Normal T No Intervention - Followed | Total |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 10 Participants | 24 Participants | 46 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 12 Participants | 10 Participants | 24 Participants | 46 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 13 | 3 / 10 | 0 / 24 |
| serious Total, serious adverse events | 0 / 13 | 0 / 10 | 0 / 24 |
Outcome results
Primary
Restricted Functional Independence Measure (FIM)
The FIM is the most widely accepted functional assessment measure in use in the rehabilitation community in the US. It is an 18-item ordinal clinician rating scale that is useful for assessment of functional skills progress during inpatient rehabilitation. It measures levels of independent/dependent performance of 13 motor functions and 5 cognitive functions. By adding the points for each item, the possible total score ranges from 18 to 126, with higher numbers indicating better performance. A restricted FIM total score that eliminated the toileting, bladder management and bowel management items was computed and used in the final analysis with scores ranging from 14-105). The restricted FIM total score was used as the primary outcome measure.
Time frame: Administered at baseline and every other week for up to 12 weeks with 7 total possible administrations.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Intervention - Treatment | Restricted Functional Independence Measure (FIM) | Baseline | 34 units on a scale |
| Intervention - Treatment | Restricted Functional Independence Measure (FIM) | Six Week | 52 units on a scale |
| Intervention Placebo | Restricted Functional Independence Measure (FIM) | Baseline | 16 units on a scale |
| Intervention Placebo | Restricted Functional Independence Measure (FIM) | Six Week | 31 units on a scale |
| No Intervention | Restricted Functional Independence Measure (FIM) | Baseline | 21 units on a scale |
| No Intervention | Restricted Functional Independence Measure (FIM) | Six Week | 36 units on a scale |
Comparison: To investigate a difference in change in outcome over time between treatment and control, a trend analysis was used in place of a profile analysis, where both control and treatment arms are described more parsimoniously i.e. by a slope (change in outcome over time) (Fitzmaurice 2011).p-value: 0.954comparison of slopes