Clinical trial NCT03554265: Brain and Gut Plasticity in Mild TBI or Post-acute COVID Syndrome Following Growth Hormone Therapy
Official title: Brain and Gut Plasticity in Mild TBI or Post-acute COVID Syndrome Following Growth Hormone Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Traumatic Brain Injury
Fatigue
Cognitive Impairment
COVID-19
Keywords: growth hormone
Traumatic Brain injury
concussion
mTBI
fatigue
cognitive impairment
BIAFAC
COVID-19
post-COVID syndrome
long hauler COVID-19
post-acute sequelae of SARS-CoV-2
Lead sponsor: The University of Texas Medical Branch, Galveston
Sponsor class: OTHER
First posted: 2018-06-13
Enrollment: 72
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: mTBI patients will be in the growth hormone arm PASC patients will be in the growth hormone arm Control subjects will be in the control arm
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: mTBI Inclusion criteria

1. Male or female with a diagnosis of mild TBI.
2. At least 6-month post-injury.
3. Ages 18 to 70 years.
4. Participant is willing and able to give informed consent for participation in the study.

mTBI Exclusion criteria

1. Unable to walk unassisted.
2. Significant heart, liver, kidney, blood or respiratory disease.
3. History of chest pain or coronary heart disease.
4. Uncontrolled Diabetes mellitus.
5. Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
6. Recent (within 6 months) treatment with anabolic steroids or corticosteroids.
7. Current alcohol or drug abuse.
8. Premorbid history of psychiatric disorder.
9. Premorbid history of head trauma.
10. Pregnancy or become pregnant during the trial.
11. Coumadin because of the risk of bleeding with daily injections of rhGH.
12. Subjects who are deficient in cortisol or thyroid at screening will be excluded until hormone abnormalities have been corrected.
13. 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.
14. Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
15. Other medical condition or medication administration deemed exclusionary by the study investigators.

Control Inclusion criteria

1. Ages 18 to 70 years.
2. Participant is willing and able to give informed consent for participation in the study.

Control Exclusion criteria

1. Significant heart, liver, kidney, blood or respiratory disease.
2. Uncontrolled Diabetes mellitus.
3. Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
4. Recent (within 6 months) treatment with anabolic steroids or corticosteroids.
5. Current alcohol or drug abuse.
6. Premorbid history of psychiatric disorder.
7. Premorbid history of head trauma.
8. Pregnancy or become pregnant during the trial.
9. Subjects who are deficient in thyroid at screening will be excluded until thyroid hormone is replaced.
10. Subjects with a history of inflammatory bowel disease, Celiac disease or active diverticular disease.
11. Other medical condition or medication administration deemed exclusionary by the study investigators.

PASC Inclusion criteria

1. Male or female with a history of COVID with diagnosis confirmed by PCR test.
2. Minimum of 6 months since diagnosis of COVID by PCR test.
3. Ages 18 to 70 years.
4. Score of 3 or higher on any question 1-3 of the Brief Fatigue Inventory (BFI) questionnaire.
5. Participant is willing and able to give informed consent for participation in the study.

PASC Exclusion criteria

1. Current COVID infection.
2. Unable to walk unassisted.
3. Significant heart, liver, kidney, blood or respiratory disease as determined by Principal Investigator.
4. Uncontrolled diabetes mellitus.
5. Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
6. Current alcohol or drug abuse.
7. History of psychosis.
8. Pregnancy or become pregnant during the trial.
9. Subjects who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.
10. Other medical condition or medication administration deemed exclusionary by the study investigators.

Primary outcomes:
measure: Lean Body Mass as Measured by Dual Energy X-Ray Absorptiometry (DEXA) at Baseline
timeFrame: baseline
measure: Lean Body Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at 6 Months
timeFrame: 6 months
measure: Fat Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at Baseline
timeFrame: baseline
measure: Fat Mass as Measured by Dual Energy X-Ra Absorptiometry (DEXA) at 6 Months
timeFrame: 6 months
Secondary outcomes:
measure: Basal Metabolic Rate as Measured by Resting Energy Expenditure at Baseline
timeFrame: baseline
measure: Basal Metabolic Rate as Measured by Resting Energy Expenditure at 6 Months
timeFrame: 6 months
Other outcomes:
measure: Cognitive Function as Measured by Montreal Cognitive Assessment at Baseline
timeFrame: baseline
measure: Cognitive Function as Measured by Montreal Cognitive Assessment at 6 Months
timeFrame: 6 months
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at Baseline
timeFrame: baseline
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 6 Months
timeFrame: 6 months
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 9 Months
timeFrame: 9 months
measure: Global Fatigue Score as Measured by Brief Fatigue Inventory (BFI) at 12 Months
timeFrame: 12 months
measure: Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at Baseline
timeFrame: baseline
measure: Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 6 Months
timeFrame: 6 months
measure: Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 9 Months
timeFrame: 9 months
measure: Personal Perception of Fatigue as Measured by Multidimensional Fatigue Symptom Inventory - Short Form at 12 Months
timeFrame: 12 months
measure: Gastrointestinal Health as Measured by the Gastrointestinal Symptom Rating Scale at Baseline
timeFrame: baseline
measure: Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale at 6 Months
timeFrame: 6 months
measure: Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale at 9 Months
timeFrame: 9 months
measure: Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale at 12 Months
timeFrame: 12 months
measure: Mood Measured by Profile of Mood States at Baseline
timeFrame: baseline
measure: Mood Measured by Profile of Mood States at 6 Months
timeFrame: 6 months
measure: Mood Measured by Profile of Mood States at 9 Months
timeFrame: 9 months
measure: Mood Measured by Profile of Mood States at 12 Months
timeFrame: 12 months
measure: Sleep Quality Measured by Pittsburgh Sleep Quality Index at Baseline
timeFrame: baseline
measure: Sleep Quality Measured by Pittsburgh Sleep Quality Index at 6 Months
timeFrame: 6 months
measure: Sleep Quality Measured by Pittsburgh Sleep Quality Index at 9 Months
timeFrame: 9 months
measure: Sleep Quality Measured by Pittsburgh Sleep Quality Index at 12 Months
timeFrame: 12 months
measure: Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Defiency in Adults at Baseline
timeFrame: baseline
measure: Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 6 Months
timeFrame: 6 months
measure: Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 9 Months
timeFrame: 9 months
measure: Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults at 12 Months
timeFrame: 12 months
measure: Depression Measured by the Beck Depression Inventory-II at Baseline
timeFrame: baseline
measure: Depression Measured by the Beck Depression Inventory-II at 6 Months
timeFrame: 6 months
measure: Depression Measured by the Beck Depression Inventory-II at 9 Months
timeFrame: 9 months
measure: Depression Measured by the Beck Depression Inventory-II at 12 Months
timeFrame: 12 months
measure: Walking Distance at 25% Perceptual Effort as Measured by Walking Test at Baseline
timeFrame: baseline
measure: Walking Distance at 25% Perceptual Effort as Measured by Walking Test at 6 Months
timeFrame: 6 months
measure: Walking Distance at 50% Perceptual Effort as Measured by Walking Test at Baseline
timeFrame: baseline
measure: Walking Distance at 50% Perceptual Effort as Measured by Walking Test at 6 Months
timeFrame: 6 months
measure: Walking Distance at 100% Effort as Measured by Walking Test at Baseline
timeFrame: baseline
measure: Walking Distance at 100% Effort as Measured by Walking Test at 6 Months
timeFrame: 6 months
Locations:
city: Galveston
country: United States
facility: University of Texas Medical Branch
state: Texas
Study officials:
affiliation: University of Texas
name: Randall J Urban, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wright TJ, Sheffield-Moore M, Pyles RB, Randolph KM, McGovern KA, Danesi CP, Lindsay SE, Zaidan MF, Masel BE, Urban RJ. Growth hormone treatment for neurologic symptoms of post-acute sequelae of COVID-19. Clin Transl Sci. 2024 Jun;17(6):e13826. doi: 10.1111/cts.13826.