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Growth Hormone Deficiency in Mild Traumatic Brain Injury

Primary Purpose

Growth Hormone Treatment, Growth Hormone Deficiency, Concussion, Mild

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Growth Hormone
Placebo
Sponsored by
University of Calgary
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Growth Hormone Treatment focused on measuring Growth Hormone Deficiency, Persistent Post-concussion Symptoms, Growth Hormone Therapy, Clinical Trial

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Sustained a concussion according to the American Congress of Rehabilitation Medicine criteria with persistent symptoms 6-months following concussion Peak growth hormone of < 3 mcg/L following glucagon stimulation test Exclusion Criteria: Untreated pituitary dysfunction Moderate/severe TBI Intracranial abnormalities Chronic neurologic conditions

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Growth Hormone

    Placebo

    Arm Description

    Participants will perform daily at-home subcutaneous GH injections after receiving thorough at-home education training provided by a pharmaceutical nurse before and research personnel. The GH will be provided be Pfizer. Starting doses will be 0.2 ug/L and 0.3 ug/L for women taking exogenous oral estrogen.

    Participants will perform daily at-home subcutaneous placebo injections after receiving thorough at-home education training provided by a pharmaceutical nurse before and research personnel. Starting doses will be 0.2 ug/L and 0.3 ug/L for women taking exogenous oral estrogen.

    Outcomes

    Primary Outcome Measures

    Baseline QoL-AGHDA
    Adult Growth Hormone Deficiency Assessment Quality of Life Questionnaire. A high score indicates a lower quality of life.
    3-months QoL-AGHDA
    Adult Growth Hormone Deficiency Assessment Quality of Life Questionnaire. A high score indicates a lower quality of life.

    Secondary Outcome Measures

    Baseline RBANS
    Repeatable Battery for the Assessment of Neuropsychological Status. A higher score indicates better outcomes.
    3-months RBANS
    Repeatable Battery for the Assessment of Neuropsychological Status. A higher score indicates better outcomes.
    Baseline GAD-7
    General Anxiety Disorder 7. A higher score indicates worse outcomes.
    3-months GAD-7
    General Anxiety Disorder 7. A higher score indicates worse outcomes.
    Baseline PHQ-9
    Personal Health Questionnaire 9. A higher score indicates worse outcomes.
    3-months PHQ-9
    Personal Health Questionnaire 9. A higher score indicates worse outcomes.
    Baseline RPQ
    Rivermead Post-Concussion Symptom Questionnaire. A higher score indicates worse outcomes.
    3-months RPQ
    Rivermead Post-Concussion Symptom Questionnaire. A higher score indicates worse outcomes.
    Baseline QoLIBRI
    Quality of Life after Brain Injury. A higher score indicates better outcomes.
    3-months QoLIBRI
    Quality of Life after Brain Injury. A higher score indicates better outcomes.
    Baseline Sleep and Concussion Questionnaire
    Sleep and Concussion Questionnaire. A higher score indicates worse outcomes.
    3-months Sleep and Concussion Questionnaire
    Sleep and Concussion Questionnaire. A higher score indicates worse outcomes.

    Full Information

    First Posted
    December 13, 2022
    Last Updated
    December 13, 2022
    Sponsor
    University of Calgary
    Collaborators
    Pfizer
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05660356
    Brief Title
    Growth Hormone Deficiency in Mild Traumatic Brain Injury
    Official Title
    Growth Hormone Deficiency in Patients With Persistent Symptoms Following Concussion
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    December 2022
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    February 2023 (Anticipated)
    Primary Completion Date
    February 2024 (Anticipated)
    Study Completion Date
    February 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    University of Calgary
    Collaborators
    Pfizer

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The goal of this randomized control trial is to test if growth hormone therapy is a safe and effective treatment for patients suffering from growth hormone deficiency and persistent post-concussion symptoms. The main questions it aims to answer are: Is growth hormone therapy effective at mitigating persisting post-concussion symptoms in patients with growth hormone deficiency? Is it feasible to conduct a larger trial to examine efficacy of growth hormone therapy in patients with persistent post-concussion symptoms and growth hormone deficiency? Participants will be asked to complete an initial assessment for study inclusion and to complete clinical outcome questionnaires. If a participant meets study criteria they will be randomized to receive either growth hormone therapy (provided by Pfizer) or a placebo (provided by Pfizer). Participants will be instructed on how to self-administer their assigned drug daily for three months. Monthly follow-up visits will include a blood draw to measure a biomarker and clinical outcome questionnaires. At the final follow-up visit after three months, participants will learn what group they were assigned and given the option to complete the growth hormone therapy if they were originally assigned to the placebo group. Researchers will compare the growth hormone therapy group to the placebo group to identify any potential differences in outcomes.
    Detailed Description
    Annually, over 250,000 Canadians and over 40 million individuals worldwide will suffer an uncomplicated concussion (head injury with no intracranial abnormalities seen on imaging). Most individuals will recover within weeks of injury but over 30% will have persistent profound symptoms (PPCS) that impedes daily function, work and social activities. To date, there are few evidence-based treatments available for patients suffering PPCS leaving patients and clinicians grasping for answers to improve health. The culminative numbers of Canadians that are living with PPCS following a concussion are staggering and symptoms impact individual's ability to work and actively contribute to society, increasing demands on health care resources, draining public supports and diminishing contribution to the national workforce. To date, there are no recommended evidence-based treatments available to improve PPCS. Current PPCS treatments are extrapolated from other conditions and often include trial and error. Hypopituitarism has been studied extensively in patients with more severe traumatic brain injuries (TBI), with growth hormone deficiency (GHD) being the most common hormone abnormality. Previous studies have examined GHD in patients with TBI due to complicated mild (evidence of intercranial abnormalities on imaging), moderate and severe TBI, but never uncomplicated mTBI (no intercranial abnormality on imaging) or concussion (terms used interchangeably in this document). These studies have shown GH therapy can significantly improve symptoms and function in patients with TBI often allowing them to return to previous work and social activities. Recent retrospective studies completed by CTD and collaborators found approximately 35-41% of patients with concussion referred for GH testing were GHD and 78% had a significant improvement in symptoms at 3 months post-treatment1. Treatment with GH provided significant improvement in symptoms, often allowing them to return to productive jobs, caregiver activities, leisure activities and greatly improving overall quality of life. This research project is incredibly important and novel as it will be the first study to prospectively follow patients with persistent symptoms following concussion to determine prevalence of growth hormone deficiency (GHD) and implement a randomized double blinded placebo controlled cross-over trial to explore the response to GH therapy. A randomized double-blinded placebo control cross-over trial will be completed to determine efficacy of GH treatment in this population as well as feasibility of a larger trial. We will recruit 20 individuals for this pilot study. Inclusion criteria will include 1) persistent symptoms 6-months following concussion and 2) Peak GH of < 3 mcg/L following glucagon stimulation test (GST). We will exclude patients with other untreated pituitary hormone deficits (gonadotrophin, TSH, ACTH, diabetes insipidus). We will perform a pilot trial in order to (1) determine GH therapy efficacy in patients with concussion and GHD and (2) assess the feasibility of a larger prospective study of this nature. We will collect demographic information, injury characteristics, symptom questionnaires, and results from GST and other endocrine testing. Primary outcome will include improvement on the QoL-AGHDA questionnaire (a quality of life questionnaire that has been validated in individuals with GHD) from baseline to 3 months following therapy. Secondary assessments will include cognition (RBANS - repeatable battery for the assessment of neuropsychological status), depression (PHQ9), anxiety (GAD7) and rivermead post-concussion symptom questionnaire (RPQ) pre-treatment and 3 months post-treatment. A Clinical follow-up and IGF-1 levels will be performed at 1 month intervals. Unblinding will occur at 3 months, and patients in the placebo group will have the opportunity to cross-over to the treatment group if they choose. Patients that cross over will complete an additional QoL-AGHDA questionnaire after three months of therapy.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Growth Hormone Treatment, Growth Hormone Deficiency, Concussion, Mild, Concussion Post Syndrome
    Keywords
    Growth Hormone Deficiency, Persistent Post-concussion Symptoms, Growth Hormone Therapy, Clinical Trial

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    Model Description
    Treatment group and placebo group. Participants assigned placebo group will be given the option to complete...
    Masking
    Participant
    Masking Description
    Participants will be masked to their assigned group. Following completion of the study, participants will be informed of their group allocation and be given the option to complete the treatment group if they were originally assigned to the placebo group.
    Allocation
    Randomized
    Enrollment
    20 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Growth Hormone
    Arm Type
    Experimental
    Arm Description
    Participants will perform daily at-home subcutaneous GH injections after receiving thorough at-home education training provided by a pharmaceutical nurse before and research personnel. The GH will be provided be Pfizer. Starting doses will be 0.2 ug/L and 0.3 ug/L for women taking exogenous oral estrogen.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will perform daily at-home subcutaneous placebo injections after receiving thorough at-home education training provided by a pharmaceutical nurse before and research personnel. Starting doses will be 0.2 ug/L and 0.3 ug/L for women taking exogenous oral estrogen.
    Intervention Type
    Drug
    Intervention Name(s)
    Growth Hormone
    Other Intervention Name(s)
    Growth Hormone Therapy
    Intervention Description
    Pfizer provided GH therapy
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Other Intervention Name(s)
    Placebo (no active therapy)
    Intervention Description
    Pfizer provided placebo
    Primary Outcome Measure Information:
    Title
    Baseline QoL-AGHDA
    Description
    Adult Growth Hormone Deficiency Assessment Quality of Life Questionnaire. A high score indicates a lower quality of life.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months QoL-AGHDA
    Description
    Adult Growth Hormone Deficiency Assessment Quality of Life Questionnaire. A high score indicates a lower quality of life.
    Time Frame
    3-months after baseline
    Secondary Outcome Measure Information:
    Title
    Baseline RBANS
    Description
    Repeatable Battery for the Assessment of Neuropsychological Status. A higher score indicates better outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months RBANS
    Description
    Repeatable Battery for the Assessment of Neuropsychological Status. A higher score indicates better outcomes.
    Time Frame
    3-months after baseline
    Title
    Baseline GAD-7
    Description
    General Anxiety Disorder 7. A higher score indicates worse outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months GAD-7
    Description
    General Anxiety Disorder 7. A higher score indicates worse outcomes.
    Time Frame
    3-months after baseline
    Title
    Baseline PHQ-9
    Description
    Personal Health Questionnaire 9. A higher score indicates worse outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months PHQ-9
    Description
    Personal Health Questionnaire 9. A higher score indicates worse outcomes.
    Time Frame
    3-months after baseline
    Title
    Baseline RPQ
    Description
    Rivermead Post-Concussion Symptom Questionnaire. A higher score indicates worse outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months RPQ
    Description
    Rivermead Post-Concussion Symptom Questionnaire. A higher score indicates worse outcomes.
    Time Frame
    3-months after baseline
    Title
    Baseline QoLIBRI
    Description
    Quality of Life after Brain Injury. A higher score indicates better outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months QoLIBRI
    Description
    Quality of Life after Brain Injury. A higher score indicates better outcomes.
    Time Frame
    3-months after baseline
    Title
    Baseline Sleep and Concussion Questionnaire
    Description
    Sleep and Concussion Questionnaire. A higher score indicates worse outcomes.
    Time Frame
    Minimum 6-months following injury (no maximum)
    Title
    3-months Sleep and Concussion Questionnaire
    Description
    Sleep and Concussion Questionnaire. A higher score indicates worse outcomes.
    Time Frame
    3-months after baseline

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Sustained a concussion according to the American Congress of Rehabilitation Medicine criteria with persistent symptoms 6-months following concussion Peak growth hormone of < 3 mcg/L following glucagon stimulation test Exclusion Criteria: Untreated pituitary dysfunction Moderate/severe TBI Intracranial abnormalities Chronic neurologic conditions
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Chantel T Debert, MD, MSc
    Phone
    4039444500
    Email
    cdebert@ucalgary.ca
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Chantel T Debert, MD, MSc
    Organizational Affiliation
    University of Calgary
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    Citations:
    PubMed Identifier
    33879807
    Citation
    Mercier LJ, Kruger N, Le QB, Fung TS, Kline GA, Debert CT. Growth hormone deficiency testing and treatment following mild traumatic brain injury. Sci Rep. 2021 Apr 20;11(1):8534. doi: 10.1038/s41598-021-87385-7.
    Results Reference
    result

    Learn more about this trial

    Growth Hormone Deficiency in Mild Traumatic Brain Injury

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