Neuroendocrine Dysfunction in Traumatic Brain Injury: Effects of Testosterone Therapy

NCT01201863 | Completed Phase 4 Results DMC

• 1 other identifier: 10 IHA 11650
• Study Type: interventional
• Target: 46
• Locations: 1 country
• Sites: 1

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.

Conditions

Endocrine Dysfunction; Trauma; Brain Injury

Keywords

Testosterone; Traumatic Brain Injury; Hypogonadism; Endocrine Dysfunction; Low Testosterone in men with new Traumatic Brain Injury

Outcome Measures

Primary Outcomes (1)

• 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.

  Administered at baseline and every other week for up to 12 weeks with 7 total possible administrations.

Study Arms (3)

Low T Intervention - Androgel Treatment

EXPERIMENTAL

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.

Drug: Androgel (Testosterone Gel)

Low T Intervention - Placebo Treatment

PLACEBO COMPARATOR

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.

Other: Placebo gel

Normal T

NO INTERVENTION

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.

Interventions

Androgel (Testosterone Gel) DRUG

2.5 gram stickpacks administered with starting dosage of 5g increasing to a max of 10g.

Low T Intervention - Androgel Treatment

Placebo gel OTHER

2.5 gram stickpacks with starting dose of 5g increasing to max of 10g.

Low T Intervention - Placebo Treatment

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Craig Hospital: lead
• University of Colorado, Denver: collaborator

Study Sites (1)

Craig Hospital

Englewood, Colorado, 80113, United States

Location

Related Publications (1)

• 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.

  PMID: 32250330 RESULT

Related Links

• Pubmed link to Testosterone replacement in hypogonadal men during inpatient rehabilitation following traumatic brain injury

MeSH Terms

Conditions

Wounds and Injuries; Brain Injuries; Brain Injuries, Traumatic; Hypogonadism

Interventions

Testosterone

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Androstenols; Androstenes; Androstanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Testosterone Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Results Point of Contact

• Title: Don Gerber, PsyD
• Organization: Craig Hospital

dgerber@craighospital.org

303-789-8478

Study Officials

• David Ripley, MD

  Rehab Institute of Chicago

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Research

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 15, 2010
• Study Start: September 1, 2010
• Primary Completion: July 1, 2014
• Study Completion: July 1, 2014
• Last Updated: July 27, 2021
• Results First Posted: July 27, 2021

Record last verified: 2021-07

Locations

US (1)