The PIT-TBI Pilot Study

Study Overview
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Brief Summary
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Damage to the pituitary gland is a frequently overlooked but potentially important complication of traumatic brain injury (TBI). Disorders of the pituitary gland can cause dysfunction of the thyroid, adrenals, ovaries and testes. These disorders may occur immediately or several months after TBI, may delay recovery and may have a significant negative impact on quality of life. TBI is the leading cause of disability and major permanent functional impairment among adults under 45 years of age. Hormonal deficits may contribute to common symptoms experienced by TBI survivors such as fatigue, poor concentration, depression and low exercise capacity. However, the association between hormonal deficits and disability remains uncertain. The primary objective of this pilot study is to assess the feasibility of a larger study that will evaluate the impact of pituitary disorders on neurological disability and functional recovery. The results of this study will provide key findings in the impact of pituitary disorders following TBI, which is a mandatory step prior testing the effect of hormonal replacement therapy in this population in costly clinical trials. If no relationship between pituitary disorders and disability is observed, the investigators' findings will prevent unnecessary, time-consuming and costly hormonal screening and will discourage potentially harmful hormonal therapy.

Official Title
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Clinical Outcomes and Predictors of PITuitary Disorders in Patients With Moderate and Severe Traumatic Brain Injury: the PIT-TBI Prospective Multicenter Pilot Cohort Study

Conditions
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Pituitary Disorders, Traumatic Brain Injury

Intervention / Treatment
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* Other: Pituitary function evaluation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 years old) Severe or moderate blunt TBI admitted to the ICU with a Glasgow Coma Scale ≤ 12 following initial resuscitation Exclusion Criteria: Previously diagnosed or suspected pituitary disorder or disease Pregnant or lactating woman Penetrating TBI Solid malignancy with life expectation <12 months Liver Cirrhosis Child C Chronic Heart Failure (New York Heart Association class IV) End-stage chronic respiratory disease (O2 dependent) End-stage renal disease (chronic dialysis or to be expected) Neurological conditions influencing functional status (e.g. spinal cord injury, neuromuscular disease, dementia, prior TBI or stroke) No fixed address Physician refusal Brain death Unable to return to the study center to attend the follow-up visits Admission to the Intensive Care Unit of the participating center > 24 hours after TBI

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Pituitary function evaluation<br>Exams performed according to a determined schedule following admission in the intensive care unit in order to determine the risk factors and the outcome associated with pituitary disorders. | Other: Pituitary function evaluation<br>* Pituitary function evaluation performed at hospital discharge, 6 and 12 months Thyroid-stimulating hormone, free T4 and T3 Follicle stimulating hormone, luteinizing hormone, estradiol, bioavailable testosterone Adrenocorticotropic hormone stimulation test Glucagon test (growth hormone deficit) Risk factors evaluation of pituitary dysfunction Demographic data Daily data (clinical exam, secondary brain injuries) Hormone levels on day 1, 3 and 7 Biomarkers on day 1, 3 and 7 Brain CT-Scan on day 1 Pituitary MRI on day 7 Outcome measures at 6 and 12 months Neurological recovery (GOSe) Independent functioning (FIM) Quality of life (EQ-5D-5L) Life satisfaction (LISAT-11) Depression (PHQ-9)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adherence to the Protocol | Percentage of participants who underwent pituitary function evaluation and outcome measures as detailed in the Assigned Interventions section | 12 months | 
| Enrollment Rate | Number of patients recruited per month per site | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological Recovery | Glasgow Outcome Scale Extended (GOSe) | 12 months | 
| Quality of life | EuroQuol - EQ-5D-5L questionnaire | 12 months | 
| Independent functioning | Functional Independence Measure (FIM) questionnaire | 12 months | 
| Depression | Patient Health Questionnaire (PHQ-9) | 12 months | 
| Life satisfaction | Life Satisfaction Questionnaire (LISAT) | 12 months | 
| Secondary hypothyroidism |  | 12 months | 
| Secondary hypogonadism |  | 12 months | 
| Secondary adrenal insufficiency |  | 12 months | 
| Growth hormone deficit |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pituitary Disorders, Traumatic Brain Injury, Critical Care, Outcome Research, Risk Factors, Patient Oriented Research