The PIT-TBI Pilot Study

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

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.

Study Overview

• Status: Unknown
• Conditions: Traumatic Brain Injury; Pituitary Disorders
• Intervention / Treatment: Other: Pituitary function evaluation

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada
    • CHU de Quebec - Hopital de l'Enfant-Jésus
  • Ontario
    • Ottawa, Ontario, Canada
      • The Ottawa Hospital
    • Toronto, Ontario, Canada
      • Sunnybrook Health Sciences Centre
  • Quebec
    • Montreal, Quebec, Canada
      • Hôpital du Sacré-Coeur de Montreal
    • Sherbrooke, Quebec, Canada
      • CHU de Sherbrooke - Hôpital Fleurimont

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Other: Pituitary function evaluation; 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; 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)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: CHU de Quebec-Universite Laval
• Collaborators: Canadian Institutes of Health Research (CIHR); Fonds de la Recherche en Santé du Québec; Canadian Critical Care Trials Group
• Investigators: Principal Investigator: François Lauzier, MD MSc FRCPC, CHU de Quebec Research Center

Publications and helpful links

General Publications

• Lauzier F, Turgeon AF, Boutin A, Shemilt M, Cote I, Lachance O, Archambault PM, Lamontagne F, Moore L, Bernard F, Gagnon C, Cook D. Clinical outcomes, predictors, and prevalence of anterior pituitary disorders following traumatic brain injury: a systematic review. Crit Care Med. 2014 Mar;42(3):712-21. doi: 10.1097/CCM.0000000000000046.

Helpful Links

• Related Info
• Related Info

Study record dates

Study Major Dates

• Study Start: March 1, 2015
• Primary Completion (Anticipated): March 1, 2018
• Study Completion (Anticipated): March 1, 2018

Study Registration Dates

• First Submitted: June 18, 2015
• First Submitted That Met QC Criteria: June 24, 2015
• First Posted (Estimate): June 25, 2015

Study Record Updates

• Last Update Posted (Actual): March 27, 2017
• Last Update Submitted That Met QC Criteria: March 24, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: Risk Factors; Traumatic Brain Injury; Critical Care; Outcome Research; Pituitary Disorders; Patient Oriented Research
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Wounds and Injuries; Endocrine System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Hypothalamic Diseases; Brain Injuries; Pituitary Diseases; Brain Injuries, Traumatic
• Other Study ID Numbers: C14-06-2040-21