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Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy

Primary Purpose

Endocrine Dysfunction, Trauma, Brain Injury

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Androgel (Testosterone Gel)
Placebo gel
Sponsored by
Craig Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Endocrine Dysfunction focused on measuring Testosterone, Traumatic Brain Injury, Hypogonadism, Endocrine Dysfunction, Low Testosterone in men with new Traumatic Brain Injury

Eligibility Criteria

16 Years - 65 Years (Child, Adult, Older Adult)MaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Craig Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

No Intervention

Arm Label

Low T Intervention - Androgel Treatment

Low T Intervention - Placebo Treatment

Normal T

Arm Description

Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to the Androgel treatment group. They underwent hormonal assays, FIM ratings and NIH Toolbox testing at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization.

Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to the Placebo gel treatment group. They underwent hormonal assays, FIM ratings and NIH Toolbox testing at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization.

A subset of men with TBI meeting study criteria with normal T at screening were assessed at all data collection time points to provide a control group. Thirty-eight men obtained normal T levels at screening of which 24 were followed.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Full Information

First Posted
September 13, 2010
Last Updated
July 6, 2021
Sponsor
Craig Hospital
Collaborators
University of Colorado, Denver
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1. Study Identification

Unique Protocol Identification Number
NCT01201863
Brief Title
Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy
Official Title
Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy
Study Type
Interventional

2. Study Status

Record Verification Date
July 2021
Overall Recruitment Status
Completed
Study Start Date
September 2010 (undefined)
Primary Completion Date
July 2014 (Actual)
Study Completion Date
July 2014 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Craig Hospital
Collaborators
University of Colorado, Denver

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Endocrine Dysfunction, Trauma, Brain Injury
Keywords
Testosterone, Traumatic Brain Injury, Hypogonadism, Endocrine Dysfunction, Low Testosterone in men with new Traumatic Brain Injury

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
46 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low T Intervention - Androgel Treatment
Arm Type
Experimental
Arm Description
Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to the Androgel treatment group. They underwent hormonal assays, FIM ratings and NIH Toolbox testing at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization.
Arm Title
Low T Intervention - Placebo Treatment
Arm Type
Placebo Comparator
Arm Description
Men with TBI meeting study criteria with Low Testosterone levels were randomly assigned to the Placebo gel treatment group. They underwent hormonal assays, FIM ratings and NIH Toolbox testing at baseline and every other week for 12 weeks during inpatient rehabilitation hospitalization.
Arm Title
Normal T
Arm Type
No Intervention
Arm Description
A subset of men with TBI meeting study criteria with normal T at screening were assessed at all data collection time points to provide a control group. Thirty-eight men obtained normal T levels at screening of which 24 were followed.
Intervention Type
Drug
Intervention Name(s)
Androgel (Testosterone Gel)
Intervention Description
2.5 gram stickpacks administered with starting dosage of 5g increasing to a max of 10g.
Intervention Type
Other
Intervention Name(s)
Placebo gel
Intervention Description
2.5 gram stickpacks with starting dose of 5g increasing to max of 10g.
Primary Outcome Measure Information:
Title
Restricted Functional Independence Measure (FIM)
Description
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.

10. Eligibility

Sex
Male
Minimum Age & Unit of Time
16 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 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; Continuously hospitalized from time of injury until admission for rehabilitation; Enrolled in study within 6 months of TBI; Receiving inpatient rehabilitation for TBI at Craig Hospital; Males between the ages of 16 to 65 (inclusive); Approval by attending physician; Testosterone level below the assay normal range; Consent to study participation Exclusion Criteria: History of any conditions that would prohibit testing contained in the NIH toolbox; Non-English or non-Spanish speaking (to the extent that would limit the ability to complete study measures); History of prior psychiatric illness requiring hospitalization; Prior testosterone therapy; History of or current or suspected hormonally dependent cancer , including carcinoma of the breast or prostate cancer; Known hypersensitivity to any T gel ingredients including alcohol and soy products; Hematocrit (HCT) greater than 55% (normal range in Colorado is up to 52) or transaminase elevation >4x upper limit of the normal range. Abnormal finding on digital rectal examination such as nodule, asymmetry, or induration (Does not include enlarged prostate or abnormal rectal tone) PSA>4.0 BMI <16 or >40kg/m2 History of untreated prolactinoma 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Ripley, MD
Organizational Affiliation
Rehab Institute of Chicago
Official's Role
Principal Investigator
Facility Information:
Facility Name
Craig Hospital
City
Englewood
State/Province
Colorado
ZIP/Postal Code
80113
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
32250330
Citation
Ripley DL, Gerber D, Pretz C, Weintraub AH, Wierman ME. Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury: Results from a double-blind, placebo-controlled clinical pilot study. NeuroRehabilitation. 2020;46(3):355-368. doi: 10.3233/NRE-192992.
Results Reference
result
Links:
URL
http://pubmed.ncbi.nlm.nih.gov/32250330/
Description
Pubmed link to Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury

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Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy

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