Growth Hormone Deficiency, Traumatic Brain Injury
Conditions
Keywords
Concussion, Persistent post-concussion symptoms, Traumatic brain injury, Growth hormone deficiency, Hypopituitarism, Quality of Life, Growth hormone replacement therapy, Post-traumatic hypopituitarism
Brief summary
The goal of this observational study is to characterize the impact of growth hormone deficiency (GHD) on quality of life, symptom burden, and sleep in adults with traumatic brain injury (TBI), and to evaluate whether these outcomes improve with growth hormone replacement therapy. The main questions it aims to answer are: * Does quality of life, as measured by the Quality of Life Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA), differ between adults with TBI and GHD compared to those with TBI and no GHD? * Do fatigue, cognition, mood, post-concussion symptoms, body image, libido, perceived stress, and sleep architecture differ between these two groups? * Among participants with GHD who begin growth hormone replacement therapy, do symptom burden and quality of life improve over a 12-week treatment period? Eligible participants will be asked to complete baseline questionnaires and undergo testing for growth hormone deficiency (glucagon stimulation testing). A subset of participants will also complete objective sleep assessments using actigraphy and at-home polysomnography. For those who are diagnosed with growth hormone deficiency and choose to pursue treatment, questionnaires will be repeated bi-weekly while receiving growth hormone replacement therap
Detailed description
Growth hormone deficiency (GHD) is the most common chronic hormone deficit following traumatic brain injury (TBI) with variable prevalence (average of 10-15%), likely a reflection of the timing and methods of testing, age, and injury severity. Previous guidelines recommend assessment of GHD with serum IGF-1. However, studies have found IGF-1 lacks specificity and sensitivity and does not correlate with dynamic testing in patients with mild TBI and GHD. The primary objective of this observational study is to determine whether the Quality of Life in Adult Growth Hormone Deficiency Assessment (QoL-AGHDA) can aid in predicting GHD in patients with mild TBI. Patients aged 18-75 years with a diagnosis of mild TBI (American congress of rehabilitation 2023 guidelines and Centre for disease control and prevention definition of traumatic brain injury) with persistent symptoms at 1-year post-injury attending the Calgary Brain Injury program and the chronic pain centre will be screened for suspected GHD by physicians. Eligible participants will complete the QoL-AGHDA along with other symptom based measures and will be referred to endocrinology for provocative testing for GHD (glucagon stimulation testing). The secondary objective is to determine if the QoL-AGHDA can provide an objective measure of growth hormone treatment efficacy in patients with TBI and GHD. To address this, participants found to have GHD (peak GH of \<3mcg/L following glucagon stimulation test) will be provided with growth hormone replacement (Genotropin, Pfizer) for 3 months. Participants will be asked to repeat questionnaires (QoL-AGHDA and additional symptom measures) bi-weekly throughout the 3-months of treatment. Exploratory sleep assessment: 1. Participants will be invited to participate in one or both optional sleep components of the study. All participants will be offered 6 consecutive days and nights of wrist actigraphy (MotionWatch8, CamNtech) following completion of the glucagon stimulation test or initial endocrinology appointment. The wrist-worn accelerometer will objectively measure sleep patterns, duration, and rest-activity cycles, while participants will complete a brief daily electronic sleep diary to capture subjective sleep characteristics. Participants diagnosed with GHD will be invited to repeat the actigraphy protocol and sleep diary after 3 months of growth hormone replacement therapy. 2. A subset of approximately 30 participants will also complete two consecutive nights of at-home polysomnography (PSG) using the Nox SAS Solution (Nox Medical, Reykjavik, Iceland). Participants will receive written and video instructions for self-application of the device. The second night of PSG will be used for analysis to characterize objective sleep architecture and identify sleep disturbances using physiological measures including brain activity, respiratory parameters, oxygen saturation, heart rate, body position, and movement. The PSG subgroup will include approximately 10 healthy controls, 10 participants with persistent symptoms following mild TBI without GHD, and 10 participants with persistent symptoms following mild TBI and GHD. Healthy controls will complete baseline demographic and medical history forms, medication use questionnaires, and the Epworth Sleepiness Scale prior to PSG.
Interventions
Not applicable (observational study)
Sponsors
University of Calgary
Pfizer
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Adults aged 18-70 years must be referred and have a diagnosis of mTBI made by a brain injury specialist physician and meet the 2023 ACRM diagnostic criteria (Appendix A, Panel A) or the NIH diagnostic criteria for moderate/severe TBI (Appendix A, Panel B). All participants must be symptomatic for at least one-year post-injury (determined by the Glasgow Extended Scale score of less than 8 for moderate/severe TBI and a Rivermead Post-Concussion Questionnaire score of \> 13 with 3 or more symptoms scored \> 3 for mTBI), at the time of screening. All participants must also be fluent in English and be able to either complete questionnaires online or over the phone. In terms of concomitant therapies and medication, all prescription and non-prescription medications (e.g., over-the-counter drugs and herbal supplements) and therapies will be recorded by participants during baseline assessments. Participants with GHD on treatment will be asked to disclose any changes in medications/and or therapies at each bi-weekly follow up questionnaires.
Exclusion criteria
include untreated pituitary deficits to minimize confounding factors (unless treated/consulted with Dr. Debert and/or Dr. Lithgow), other intracranial abnormalities, chronic neurological conditions, untreated medical conditions, major medical conditions in the past 6 months such as stroke, and current or planned pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Quality of Life in Adult Growth Hormone Deficiency Assessment (Qol-AGHDA) | To be completed at baseline and repeated bi-weekly during Genotropin treatment and treatment completion (3 months) | A 25-question, self-administered, condition specific quality of life measure used to determine the extent to which growth hormone deficiency has affected the patient's quality of life. Participants are instructed to answer "yes" or "no" to statements relating to problems with memory and concentration, tiredness, tenseness, social isolation and self-confidence. Higher scores indicate greater symptom burden and lower quality of life. |
| Glucagon Stimulation Testing | Baseline | Provocative glucagon stimulation testing completed by endocrinology. Peak growth hormone of less than 3mcg/L indicative of growth hormone deficiency |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Saint Louis University Mental Status Examination (SLUMS) | To be assessed at baseline and at completion of treatment (3 months) | Assesses for mild cognitive impairment. Total possible score ranges from 0 to 30, with higher scores indicative of better outcomes. |
| Fatigue and Altered Cognition Scale (FACS) | To be repeated bi-weekly during Genotropin treatment and treatment completion (3 months) | A 20-item self-reported questionnaire that measures central fatigue and altered cognition, , with 10 items comprising each subscale. Items are rated on an electronic visual analog scale (0-100), with higher scores indicating greater symptom severity. |
| Patient Health Questionnaire - 9 (PHQ-9) | To be assessed at baseline, bi-weekly during Genotropin treatment and at completion of treatment (3 months) | Assesses depressive symptoms. Total possible score ranges from 0-27, with higher scores indicative of worse outcomes. |
| Generalized Anxiety Disorder -7 (GAD-7) | To be assessed at baseline, bi-weekly during Genotropin treatment and at completion of treatment (3 months) | Assesses feelings of anxiety. Total possible score ranges from 0-21, with higher scores indicative of worse outcomes. |
| Rivermead Post-Concussion Symptom Questionnaire (RPQ) | To be assessed at baseline, bi-weekly during Genotropin treatment and at completion of treatment (3 months) | Assesses the severity of 16 commonly experienced PCS symptoms. Participants are instructed to rate the extent to which they have suffered from each of the listed symptoms in the past 24 hours, as compared to pre-injury levels, using a scale of 0 ("not experienced at all") to 4 ("a severe problem"). The RPQ has been demonstrated as a valid measure of PPCS with a minimal clinically important difference (MCID) of 4.5 points. It is advised to analyze this assessment as two separate scales (RPQ-13 and RRQ-3). The RPQ-3 has a total possible score of 0-12, with higher scores indicative of worse outcomes. The RPQ-13 has a total possible score of 0-52, with higher scores indicative of worse outcomes. Using these sub-scales, the instrument has good test-retest reliability and external construct validity. This questionnaire probes the separate cognitive, emotional and somatic components of PPCS. |
| Glasgow outcome scale extended (GOSE) | To be assessed at baseline, bi-weekly during Genotropin treatment and at completion of treatment (3 months) | Assesses outcomes following brain injury. Scores range from 1 to 8 with higher scores meaning better outcomes. |
| Sleep and Concussion Questionnaire | To be assessed at baseline, bi-weekly during Genotropin treatment and at completion of treatment (3 months) | A self-reported 6-item questionnaire to identify and quantify changes in sleep in response to concussion and monitor these changes over time. |
| Sexual Desire Inventory (SDI | To be assessed at baseline, 4-weeks post-treatment starts and at completion of treatment (3 months) | A 14-item self-report tool that measures sexual desire, distinguishing between dyadic (with others) and solitary (by oneself) desire. This provides insight into sexual motivation, and any changes over time. |
| Godin Leisure-Time Questionnaire: | To be assessed at baseline and at completion of treatment (3 months) | A brief self-report tool that measures frequency of mild, moderate, and strenuous physical activity during free time in a typical week, and how this has changed following injury. |
| Body Image Scale (BIS): | To be assessed at baseline, 4-weeks post-treatment starts and at completion of treatment (3 months) | A 10-item self-report questionnaire that assesses affective, behavioral, and cognitive aspects of body image perception. |
| Epworth Sleepiness Scale (ESS) | To be assessed at baseline, 4-weeks post-treatment starts and at completion of treatment (3 months) | An 8-item self-report questionnaire that assesses daytime sleepiness by rating the likelihood of dozing in common daily situations, producing a total score where higher values indicate greater levels of daytime sleepiness. |
| Perceived Stress Scale (PSS) | To be assessed at baseline, treatment start, 4-weeks post-treatment start and at completion of treatment (3 months) | A 10-item self-report questionnaire that evaluates the degree to which individuals perceive their lives as unpredictable, uncontrollable, and overwhelming over the past month. Respondents rate how often they experienced specific thoughts and feelings on a 5-point Likert scale (0 = never to 4 = very often), with total scores ranging from 0 to 40, where higher scores indicate greater perceived stress. |
| Waist Circumference: | To be assessed at baseline and at completion of treatment (3 months) | Waist circumference will be measured using a flexible measuring tape placed midway between the last rib and the top of the iliac crest, with the participant standing comfortably. The measurement will be recorded to the nearest 0.1 cm. |
| Hand Grip Strength | To be assessed at baseline and at completion of treatment (3 months) | Hand grip strength will be assessed using a hand grip dynamometer. Participants will complete three trials with each hand, and the average of the three trials for each hand will be calculated and used for analysis. |
| Wrist Based Actigraphy | If participants have GHD, they will be asked to repeat the same actigraphy protocol for 6 nights/days with daily sleep diary completion at the 3-month post treatment mark. | At the time of the GST or initial endocrinology appointment, all participants will be asked to wear a wrist-based actigraph on their non-dominant hand (MotionWatch8, CamNtech), an accelerometer that tracks movement and activity, for six consecutive days and nights after the GST has been completed. During each actigraphy recording period, participants will complete a brief daily digital sleep diary. This will allow for objective measurement of sleep patterns, duration, and rest-activity cycles, which will be compared with participants' subjective perceptions of sleep recorded in the sleep diary. |
| At-home polysomnography (PSG) | Baseline | A subset of participants will be invited to complete a two-night at-home sleep study using a portable polysomnography device (Nox SAS Solution, Nox Medical, Reykjavik, Iceland). The Nox device records multiple sleep-related physiological signals during sleep, including breathing patterns, oxygen saturation, heart rate, body position, and movement. Participants will be provided with video and written instructions to guide them through the self-setup of the device and sensors prior to the recording period. The sleep study will be completed in the participant's home over two consecutive nights. Data collected from the Nox system will be used to characterize objective sleep patterns and identify potential sleep disturbances. Approximately 30 participants will be recruited for this exploratory component, including: 10 healthy controls with no history of concussion or traumatic brain injury, 10 participants with persisting symptoms following mTBI without GHD, 10 participants with GHD \& mTBI |
Countries
Canada
Contacts
CONTACTChantel T Debert, MD MSc FRCPC CSCN
CONTACTChristina Campbell, MSc
PRINCIPAL_INVESTIGATORChantel T Debert, MD MSc FRCPC CSCN
University of Calgary
Outcome results
None listed