Brain and Gut Plasticity in Mild TBI or Post-acute COVID Syndrome Following Growth Hormone Therapy
Study Details
Study Description
Brief Summary
Patients with a history of mild traumatic brain injury (mTBI) or post acute sequelae of SARS-CoV-2 (PASC) and abnormal growth hormone secretion, as measured by glucagon stimulation test, will be treated with replacement growth hormone therapy for a period of 6 months (mTBI) or 9 months (PASC). Testing of cognition, exercise, fatigue, brain activation and morphology, body composition and measurements of quality of life will be performed before and after the treatment period. Fecal sampling for characterization of the GI microbiome will occur monthly over the treatment period. Control subjects will be enrolled and will provide fecal samples monthly for 6 months. GI microbiomes will be compared between mTBI patients, PASC patients and controls at baseline as well as over the treatment period.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
The investigators will study subjects (aged 18-70 years) with a history of mild TBI (n=25), post-acute sequelae of SARS-CoV-2 (PASC) (n=25)and healthy controls (n=25). mTBI subjects will undergo a 6-month intervention of rhGH therapy. PASC subjects will undergo a 9-month intervention of rhGH therapy. Controls will be asked to participate in questionnaires, blood draws (amino acid analysis), and fecal sampling (GI microbiome analysis). Controls will not receive any growth hormone treatment.
mTBI group
All patients presenting with a prior mTBI will undergo a phone pre-screen including the Brief Fatigue Inventory (BFI) questions 1-3. If they score ≥ 3 on any BFI questions 1-3, and are interested in participating in the study, they will be scheduled for a formal consenting and medical screening at the UTMB Clinical Research Center (CRC). During the medical screening, eligibility will be confirmed and a glucagon stimulation test (GST) will be performed. A glucagon stimulation with a growth hormone peak of <10 ng/mL is required to qualify for enrollment.
PASC group
All patients presenting with PASC will undergo a phone pre-screen including the Brief Fatigue Inventory (BFI) questions 1-3. If they score ≥ 3 on any BFI questions 1-3, and are interested in participating in the study, they will be scheduled for a formal consenting and medical screening at the UTMB Clinical Research Center (CRC). During the medical screening, eligibility will be confirmed and a glucagon stimulation test (GST) will be performed. A glucagon stimulation with a growth hormone peak of <10 ng/mL is required to qualify for enrollment.
Control group
All controls will undergo a phone pre-screen and if interested in participating in the study, will be scheduled for a formal consenting and medical screening at the UTMB Clinical Research Center (CRC).
Experimental Protocol.
mTBI Group
Before and at completion (month 6) of the rhGH intervention, mTBI subjects will report to the UTMB Institute for Translational Sciences (ITS) Clinical Research Center (CRC) for testing, which will consist of cognitive function assessment (MoCA), determination of brain morphology and connectivity using fMRI, determination of lean mass and fat mass using DEXA, resting energy expenditure, functional testing including leg strength and 6 minute walk test, fatigue measurements, and questionnaires of mood and quality of life, gastrointestinal health, sleep, and food preferences. Blood sampling for measurement of amino acid levels, hormones, and metabolites will be drawn before and 90 minutes (+/- 10 minutes) after a standardized meal. In addition, fecal samples for analysis of the GI microbiome will be collected monthly for the duration of the study. Insulin Growth Factor 1 (IGF-1) levels will monitored at a month 1 safety visit for all mTBI subjects. The month 1 safety visit will occur +/- 5 days from the expected date based on the baseline study visit. The monthly fecal sampling will occur +/- 7 days from the expected date based on the baseline study visit. The month 6 post study will occur +/- 7 days from the expected date based on the baseline study visit. A member of the study team will contact the subject each month to coordinate fecal sample transport to UTMB, check for adverse events and overall well-being, and ensure compliance and ongoing consent.
PASC Group
Before and at month 6 of the rhGH intervention, PASC subjects will report to the UTMB Institute for Translational Sciences (ITS) Clinical Research Center (CRC) for testing, which will consist of cognitive function assessment (MoCA), determination of lean mass and fat mass using DEXA, resting energy expenditure, functional testing including leg strength and 6 minute walk test, fatigue measurements, and questionnaires of mood and quality of life, gastrointestinal health, sleep, and food preferences. Blood sampling for measurement of amino acid levels, hormones, and metabolites will be drawn before and 90 minutes (+/- 10 minutes) after a standardized meal. In addition, fecal samples for analysis of the GI microbiome will be collected monthly for the duration of the study. Insulin Growth Factor 1 (IGF-1) levels will monitored at a month 1 safety visit for all mTBI subjects. The month 1 safety visit will occur +/- 5 days from the expected date based on the baseline study visit. The monthly fecal sampling will occur +/- 7 days from the expected date based on the baseline study visit. The month 6 post study will occur +/- 7 days from the expected date based on the baseline study visit. PASC subjects will continue on rhGH treatment for an additional 3 months. GI microbiome sampling and questionnaires will occur at month 9 and month 12. PASC subjects will have an repeat glucagon stimulation test (GST) to determine growth hormone status at month 12. A member of the study team will contact the subject each month to coordinate fecal sample transport to UTMB, check for adverse events and overall well-being, and ensure compliance and ongoing consent.
Control group
Before and at month 6, controls will report to the UTMB Institute for Translational Sciences (ITS) Clinical Research Center (CRC) for testing, which will consist of questionnaires of food preferences and gastrointestinal health and blood sampling for measurement of amino acid levels, hormones, and metabolites which will be drawn before and 90 minutes (+/ 10 minutes) after a standardized meal. In addition, fecal samples for the analysis of the GI microbiome will be collected monthly for the duration of the study, as well as questionnaire assessing gastrointestinal health. The monthly fecal sampling will occur +/- 7 days from the expected date based on the baseline study visit. The post study (month 6) will occur +/- 7 days from the expected date based on the baseline study visit. A member of the study team will contact the subject each month to coordinate fecal sample transport to UTMB, check for adverse events and overall well-being, and ensure compliance and ongoing consent.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: mTBI subjects mTBI subjects will receive recombinant human growth hormone replacement therapy daily for 6 months. Drug: recombinant human growth hormone (rhgH); somatropin, Genotropin Dose: month 0 - month 1 will be dosed at 0.4 mg / day month 1 - month 6 will be dosed at 0.6 mg / day |
Drug: Somatropin
Genotropin given by injection
Other Names:
|
| No Intervention: Household Control Subjects household control subjects will not receive any intervention. |
|
| Experimental: PASC subjects PASC subjects will receive recombinant human growth hormone replacement therapy daily for 9 months. Drug: recombinant human growth hormone (rhgH); somatropin, Genotropin Dose: month 0 - month 1 will be dosed at 0.4 mg / day month 1 - month 9 will be dosed at 0.6 mg / day |
Drug: Somatropin
Genotropin given by injection
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Lean Body Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at Baseline [baseline]
Lean body mass will be measured in mTBI and PASC subjects by GE Lunar iDEXA at baseline.
- Lean Body Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at 6 months [6 months]
Lean body mass will be measured in mTBI and PASC subjects by GE Lunar iDEXA after 6 months of growth hormone treatment.
- Fat Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at Baseline [baseline]
Fat mass will be measured in mTBI and PASC subjects by GE Lunar iDEXA at baseline.
- Fat Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at 6 months [6 months]
Fat mass will be measured in mTBI and PASC subjects by GE Lunar iDEXA after 6 months of growth hormone treatment.
Secondary Outcome Measures
- Basal Metabolic rate as measured by Resting Energy Expenditure at baseline [baseline]
Resting Energy Expenditure will be measured by capturing the expired breath of mTBI and PASC subjects while at rest with a metabolic cart over a 30 minute time period. Data will be reported as kilocalories/day.
- Basal Metabolic rate as measured by Resting Energy Expenditure at 6 months [6 months]
Resting Energy Expenditure will be measured by capturing the expired breath of mTBI and PASC subjects while at rest with a metabolic cart over a 30 minute time period. Data will be reported as kilocalories/day. This will be measured after 6 months of growth hormone treatment in mTBI and PASC subjects only.
Other Outcome Measures
- Cognitive Function as measured by Montreal Cognitive Assessment at baseline [baseline]
The Montreal Cognitive Assessment (MoCA) will be used to assess cognition at baseline in mTBI and PASC subjects only. The Montreal Cognitive Assessment (MoCA) is a rapid assessment of cognition. The MoCA consists of 9 questions with the following subcategories: visuospatial/executive, naming, memory, language, abstraction, delayed recall and orientation. The MoCA has been used extensively to detect cognitive impairment in many conditions, including head trauma. Version 7.1 will be used at the Month 0 testing and Version 7.2 will be used at the Month 6 testing. Scores range from 0 to 30, higher score being a better outcome.
- Cognitive Function as measured by Montreal Cognitive Assessment at 6 months [6 months]
The Montreal Cognitive Assessment (MoCA) will be used to assess cognition after 6 months of growth hormone treatment in mTBI and PASC subjects only. The Montreal Cognitive Assessment (MoCA) is a rapid assessment of cognition. The MoCA consists of 9 questions with the following subcategories: visuospatial/executive, naming, memory, language, abstraction, delayed recall and orientation. The MoCA has been used extensively to detect cognitive impairment in many conditions, including head trauma. Version 7.1 will be used at the Month 0 testing and Version 7.2 will be used at the Month 6 testing. Scores range from 0 to 30, higher score being a better outcome.
- Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at baseline [baseline]
The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Brief Fatigue Inventory is measured in mTBI and PASC subjects at baseline.
- Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 6 months [6 months]
The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Brief Fatigue Inventory is measured in mTBI and PASC subjects after 6 months of growth hormone treatment.
- Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 9 months [9 months]
The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Brief Fatigue Inventory is measured in PASC subjects after 9 months of growth hormone treatment.
- Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 12 months [12 months]
The Brief Fatigue Inventory is a 9 item questionnaire that assesses perceptual fatigue as well as fatigue interferences (e.g. interference with enjoyment of life), with "0" being no fatigue and "10" being as bad as you can imagine. The Global Fatigue score is calculated by averaging the answers of all the questions. Brief Fatigue Inventory is measured in PASC subjects after 9 months of growth hormone treatment and 3 months off treatment (total time: 12 months).
- Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at Baseline [baseline]
Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. The MFSI is measured at baseline.
- Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 6 months [6 months]
Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. The MFSI is measured after 6 months of growth hormone treatment.
- Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 9 months [9 months]
Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. The MFSI is measured after 9 months of growth hormone treatment in PASC subjects only.
- Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 12 months [12 months]
Multidimensional Fatigue Symptom Inventory Short Form (MFSI-SF) from the Moffitt Cancer Center, University of South Florida The MFSI-SF is a 30 question assessment designed to assess the principal manifestations of fatigue. There 5 subscales used to calculate a total score. The subscales are: General Fatigue, Physical Fatigue, Emotional Fatigue, Mental Fatigue, and Vigor (an estimate of the patient's energy level). The total score is calculated with the equation: (general + physical + emotional + mental) - vigor = total score. The range of the total score is -24 to 96, with the higher the number meaning more fatigue. The MFSI is measured after 9 months of growth hormone treatment and then 3 months without treatment (total 12 months) in PASC subjects only.
- Gastrointestinal Health as measured by the gastrointestinal symptom rating scale at baseline [baseline]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly at baseline mTBI, PASC and control subjects.
- Gastrointestinal Health as measured by the gastrointestinal symptom rating scale at 1 month [1 month]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly in all subjects.
- Gastrointestinal Health as measured by the gastrointestinal symptom rating scale at 2 months [2 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly in all subjects.
- Gastrointestinal Health as measured by the gastrointestinal symptom rating scale at 3 months [3 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly in all subjects.
- Gastrointestinal Health as measured by the gastrointestinal symptom rating scale at 4 months [4 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly all subjects.
- Gastrointestinal Health measured by the gastrointestinal symptom rating scale at 5 months [5 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly in all subjects.
- Gastrointestinal Health measured by the gastrointestinal symptom rating scale at 6 months [6 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured monthly in all subjects.
- Gastrointestinal Health measured by the gastrointestinal symptom rating scale at 9 months [9 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured in month 9 in PASC subjects only.
- Gastrointestinal Health measured by the gastrointestinal symptom rating scale at 12 months [12 months]
The Gastrointestinal Symptom Rating Scale (GSRS) is a specific 15-item questionnaire. Subjects are asked to numerically score their subjective symptoms on a scale of 1-7 (1 = no discomfort at all; 7 = very severe discomfort) . The sum of the scores for all 15 items is regarded as the GSRS total score. Total scores range from 15 (best outcome) to 105 (worst outcome). GSRS will be measured in month 12 in PASC subjects only.
- Mood Measured by Profile of Mood States at Baseline [baseline]
Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being "not at all' and 4 being "extremely". There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). POMS will be measured at baseline in mTBI and PASC subjects only.
- Mood Measured by Profile of Mood States at 6 months [6 months]
Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being "not at all' and 4 being "extremely". There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). POMS will be measured after 6 months of treatment with Growth hormone in mTBI and PASC subjects only.
- Mood Measured by Profile of Mood States at 9 months [9 months]
Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being "not at all' and 4 being "extremely". There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). POMS will be measured after 9 months of treatment with Growth hormone in PASC subjects only.
- Mood Measured by Profile of Mood States at 12 months [12 months]
Profile of Mood States (POMS) is a questionnaire by MultiHealth Systems, that measures mood. In this 65 item questionnaire, subjects are asked to rate their feelings toward a statement from 0-4, with 0 being "not at all' and 4 being "extremely". There are 6 subscales which include, tension-anxiety, depression, anger-hostility, vigor, fatigue, and confusion. To calculate the total mood disturbance, which is what is reported here, the subscales tension-anxiety, depression, anger-hostility, fatigue and confusion are summed and vigor is subtracted. The scale range for total mood disturbance is 200 (worst) to -32 (best). POMS will be measured after 9 months of treatment with Growth hormone treatment and 3 months without treatment (total 12 months) in PASC subjects only.
- Sleep Quality measured by Pittsburgh Sleep Quality Index at baseline [baseline]
Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total < 5 associated with good sleep quality. Total > 5 associated with poor sleep quality. PSQI will be measured at baseline in mTBI and PASC subjects only.
- Sleep Quality measured by Pittsburgh Sleep Quality Index at 6 months [6 months]
Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total < 5 associated with good sleep quality. Total > 5 associated with poor sleep quality. PSQI will be measured after 6 months of treatment with growth hormone in mTBI and PASC subjects only.
- Sleep Quality measured by Pittsburgh Sleep Quality Index at 9 months [9 months]
Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total < 5 associated with good sleep quality. Total > 5 associated with poor sleep quality. PSQI will be measured after 9 months of treatment with growth hormone in PASC subjects only.
- Sleep Quality measured by Pittsburgh Sleep Quality Index at 12 months [12 months]
Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1 month-time interval. Minimum Score = 0 (better); Maximum Score = 21 (worse). Interpretation: Total < 5 associated with good sleep quality. Total > 5 associated with poor sleep quality. PSQI will be measured after 9 months of treatment with growth hormone and 3 months without treatment (total 12 months) in PASC subjects only.
- Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Defiency in Adults at baseline [baseline]
Symptoms of growth hormone deficiency will be measured in mTBI and PASC subjects using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms. The QoL-ADGHA will be measured at baseline in mTBI and PASC subjects only.
- Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 6 months [6 months]
Symptoms of growth hormone deficiency will be measured in mTBI and PASC subjects using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms. The QoL-ADGHA will be measured after 6 months of growth hormone treatment in mTBI and PASC subjects only.
- Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 9 months [9 months]
Symptoms of growth hormone deficiency will be measured in PASC subjects using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms. The QoL-ADGHA will be measured after 9 months of growth hormone treatment in PASC subjects only.
- Symptoms of Growth Hormone Deficiency measured by the questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 12 months [12 months]
Symptoms of growth hormone deficiency will be measured in PASC subjects using the Quality of Life - Assessment of Growth Hormone Deficiency in Adults (QoL-AGHDA). This 25-item questionnaire measures specific symptoms associated with growth hormone deficiency, with a score range of 0 to 25, with a higher score indicating worse symptoms. The QoL-ADGHA will be measured after 9 months of growth hormone treatment and then 3 months without treatment (total 12 months) in PASC subjects only.
- Depression measured by the Beck Depression Inventory-II at baseline [baseline]
The Beck Depression Inventory- II assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe. The BDI will be measured at baseline in mTBI and PASC subjects only.
- Depression measured by the Beck Depression Inventory-II at 6 months [6 months]
The Beck Depression Inventory- II assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe. The BDI will be measured after 6 months of growth hormone treatment in mTBI and PASC subjects only.
- Depression measured by the Beck Depression Inventory-II at 9 months [9 months]
The Beck Depression Inventory- II assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe. The BDI will be measured after 9 months of growth hormone treatment in PASC subjects only.
- Depression measured by the Beck Depression Inventory-II at 12 months [12 months]
The Beck Depression Inventory- II assesses depressive symptom severity. The BDI-II is comprised of 21 individual items reflecting specific cognitive, affective, and physical symptoms of depression. Each item includes four statements that vary in the description of symptom of severity. Scores range from 0 to 3, with a score of "3" indicating a severe symptoms and a score of "0" indicating an absence of concern with that particular aspect of depressive symptomology. The total score is the sum of all endorsed statements. The maximum total score is 63. The BDI-II Manual designates the following raw score classifications depression severity: ≤13 = minimal; 14-19 = mild; 20-28 = moderate; ≥ 29 = severe. The BDI will be measured after 9 months of growth hormone treatment and 3 months without treatment (total 12 months) in PASC subjects only.
- Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 at Baseline [baseline]
Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 15 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength will be measured at baseline. Measured in mTBI and PASC subjects only.
- Maximum Peak Isometric Leg Strength as Measured by Biodex Pro4 at 6 months [6 months]
Peak isometric strength is measured on a Biodex System 4 Pro. This test is isolated to the quadricep muscle of one leg. Isometric test is performed at 90 degrees with 15 seconds of force production for each contraction and 15 seconds of rest. 1 set of 3 contractions at 100% force performed. Isometric strength will be measured after 6 months of growth hormone treatment. Measured in mTBI and PASC subjects only.
- Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 at baseline [baseline]
Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured at baseline. Measured in mTBI and PASC subjects only.
- Maximum Peak Isokinetic Leg Strength as Measured by Biodex Pro4 at 6 months [6 months]
Isokinetic strength (knee extension) is measured on a Biodex System Pro 4 within a 75 degree range of motion. Subjects performed concentric contractions at a fixed speed of 120 degree/sec. 1 set of 3 contractions were performed at 100% force. Isokinetic strength will be measured after 6 months of growth hormone treatment. Measured in mTBI and PASC subjects only.
- Walking Distance at 25% Perceptual Effort as measured by walking test at baseline [baseline]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at baseline. Measured in mTBI and PASC subjects only.
- Walking Distance at 25% Perceptual Effort as measured by walking test at 6 months [6 months]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at month 6. Measured in mTBI and PASC subjects only.
- Walking Distance at 50% Perceptual Effort as measured by walking test at baseline [baseline]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at baseline. Measured in mTBI and PASC subjects only.
- Walking Distance at 50% Perceptual Effort as measured by walking test at 6 months [6 months]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at month 6. Measured in mTBI and PASC subjects only.
- Walking Distance at 100% Effort as measured by walking test at baseline [baseline]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at baseline. Measured in mTBI and PASC subjects only.
- Walking Distance at 100% Effort as measured by walking test at 6 months [6 months]
Walking performance will be assessed in mTBI and PASC patients during 6 minutes of walking in long corridor hallways. This is a standard test of walking performance that has been validated in similar studies. Here, the test will be slightly modified, with subjects asked to walk at a 25% perceived effort from minute 0 - 2, at a 50% perceived effort from minute 2 - 4, and at a 100% effort (as quickly as they can safely walk without running) from minute 4 -6. Distance traveled for each 2-minute category will be recorded. The 6-minute walking test will be completed at month 6. Measured in mTBI and PASC subjects only.
Eligibility Criteria
Criteria
mTBI Inclusion criteria
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Male or female with a diagnosis of mild TBI.
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At least 6-month post-injury.
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Ages 18 to 70 years.
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Participant is willing and able to give informed consent for participation in the study.
mTBI Exclusion criteria
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Unable to walk unassisted.
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Significant heart, liver, kidney, blood or respiratory disease.
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History of chest pain or coronary heart disease.
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Uncontrolled Diabetes mellitus.
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Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
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Recent (within 6 months) treatment with anabolic steroids or corticosteroids.
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Current alcohol or drug abuse.
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Premorbid history of psychiatric disorder.
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Premorbid history of head trauma.
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Pregnancy or become pregnant during the trial.
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Coumadin because of the risk of bleeding with daily injections of rhGH.
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Subjects who are deficient in cortisol or thyroid at screening will be excluded until hormone abnormalities have been corrected.
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Subjects with chronic pain who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.
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Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
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Other medical condition or medication administration deemed exclusionary by the study investigators.
Control Inclusion criteria
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Ages 18 to 70 years.
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Participant is willing and able to give informed consent for participation in the study.
Control Exclusion criteria
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Significant heart, liver, kidney, blood or respiratory disease.
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Uncontrolled Diabetes mellitus.
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Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
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Recent (within 6 months) treatment with anabolic steroids or corticosteroids.
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Current alcohol or drug abuse.
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Premorbid history of psychiatric disorder.
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Premorbid history of head trauma.
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Pregnancy or become pregnant during the trial.
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Subjects who are deficient in thyroid at screening will be excluded until thyroid hormone is replaced.
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Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
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Other medical condition or medication administration deemed exclusionary by the study investigators.
PASC Inclusion criteria
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Male or female with a history of COVID with diagnosis confirmed by PCR test.
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Minimum of 6 months since diagnosis of COVID by PCR test.
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Ages 18 to 70 years.
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Score of 3 or higher on any question 1-3 of the Brief Fatigue Inventory (BFI) questionnaire.
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Participant is willing and able to give informed consent for participation in the study.
PASC Exclusion criteria
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Current COVID infection.
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Unable to walk unassisted.
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Significant heart, liver, kidney, blood or respiratory disease as determined by Principal Investigator.
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Uncontrolled diabetes mellitus.
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Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
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Current alcohol or drug abuse.
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History of psychosis.
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Pregnancy or become pregnant during the trial.
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Subjects who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.
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Other medical condition or medication administration deemed exclusionary by the study investigators.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University of Texas Medical Branch | Galveston | Texas | United States | 77555 |
Sponsors and Collaborators
- The University of Texas Medical Branch, Galveston
Investigators
- Principal Investigator: Randall J Urban, MD, University of Texas
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- 17-0313