Scientific title
Pituitary gland deficiencies after traumatic brain injury: An Outcomes and Prevalence Study
Acronym
PitSTOP
Study hypothesis
Post- traumatic brain injury (anterior) pituitary gland dysfunction (PTPD) is common following traumatic brain injury and clinical and radiological factors at the time of trauma may predict the risk of developing long-term PTPD.
Ethics approval
South East Scotland Regional Ethics Committee 02, 18/07/2017, ref: 17/SS/0043
Study design
Multi-centre cross-sectional longitudinal cohort study
Primary study design
Observational
Secondary study design
Cross sectional study
Trial setting
Hospitals
Trial type
Diagnostic
Patient information sheet
See additional fiels
Condition
Traumatic brain injury
Intervention
After informed consent, recruited participants have blood tests to assess the function of their brain. These tests are all performed between 8am and 10am and the patients have to be ‘fasted’ (nothing to eat from midnight the night before) before the blood test. The blood tests are performed at four stages during follow up:
Stage 1. In the first week after Traumatic brain injury (TBI)
Stage 2. Within the first month after TBI
Stage 3. At six months after TBI
Stage 4. At 12 months after TBI
Baseline levels of the following hormones are checked at all 4 stages. These include tests for: cortisol, insulin-like growth factor 1 (IGF-1), growth hormone (GH), prolactin, sodium, thyroid-stimulation hormone (TSH) and free thyroxine (fT4), testosterone levels in men and oestrogen levels in premenopausal women who do not have a regular menstrual cycle. All of these blood tests can be performed using 3.5mLs (approximately half a tablespoon) of blood.
Also, during the first stage, a subset of participants will also have an magnetic resonance imaging (MRI) of their brain. These scans will be done at every stage of follow-up and will be done on the same day that the patients have their blood test. The MRI scans will be done to check whether there are any structural changes in the pituitary gland that can help predict likelihood of developing long-term PTPD.
The MRI protocol lasts less than 30 minutes and will include the following sequences: T1-weighted 3-D volumetric sequences of the whole brain T2-weighted 2D sequences of the whole brain 3-D Susceptibility weighted imaging (SWI) sequences of the whole brain T1-weighted and T2-weighted fine slices (2mm) of pituitary gland 30 direction diffusion-tensor imaging (DTI) with axial and sagittal sequences
During the second, third and fourth stages of follow up, in addition to the baseline blood tests, participants also have stimulation tests for growth hormone deficiencies (GHD) and secondary hypoadrenaism (SH):
1. Stimulation test for GHD:
GHRH + Arginine test is used to test for GHD. During this test, a dose of a hormone called growth hormone release hormone (GHRH) (1 micrograms per Kg) is given with a protein called Arginine ( 30g in 100mLs) as an infusion over 30 minutes. Blood samples to check GH levels are then taken at 30 minutes and at 60 minutes after the start of the infusion.
2. Stimulation test for SH:
Short Synacthen test (SST) is used to test for SH. During this test, a sample of blood is taken and then an intramuscular injection (into muscle, usually the shoulder muscle) of Synacthen is given. Synacthen is a synthetic hormone that mimics one of the hormones of the pituitary gland called ACTH. After it has been injected, two further blood tests are done 30 minutes and 60 minutes after the injection to analyse whether the Synacthen has caused an appropriate rise in the level of a hormone called cortisol.
The injections that are given during the stimulation tests are either naturally occurring or synthetic versions of naturally occurring substances. They are tolerated by most patients but the tests are done under the supervision of an appropriate clinician, in case of any adverse reactions.
The patients selected to have an MRI scan at the first stage have the scan repeated at all follow ups stages. Finally, during the third and fourth stages, participants are asked to complete the extended Glasgow Outcome Score (GOSE) to assesses functional recovery following TBI.
This feasibility study is planned to test all aspects of the PitSTOP protocol prior to starting the main study. During this feasibility study, the first follow up stage will be omitted.
Intervention type
Biological/Vaccine
Phase
Drug names
Primary outcome measures
Prevalence of post TBI pituitary gland dysfunction (PTPD) is measured with pituitary function test (baseline measurements of serum thyroid stimulating hormone, free T4, testosterone, IGF-1 and cortisol) acutely (within 7 days), sub-acutely (within one month) and long-term (up to 6 months and up to 12 months) after TBI. Also a short synacthen test and GHRH + Arginine tests will be performed in the sub-acutely (within one month) and long-term (6 month and 12 months).
Secondary outcome measures
1. Clinical and radiological markers are measured using the clinical information available at the time of presentation to hospital and serial MRI of the pituitary gland performed acutely, within one month and long-term (6 to 12 months) in a subset of patients to try to predict the occurrence of PTPD
2. Optimal timing for surveillance for PTPD using the clinical and radiological information detailed above
3. Functional recovery of patients with PTPD using Glasgow Outcome Score (eGOS) at end of study period (six to 12 months)
Overall trial start date
01/09/2016
Overall trial end date
01/08/2020
Reason abandoned
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