Brain and Gut Plasticity in Mild TBI or Post-acute COVID Syndrome Following Growth Hormone Therapy

Phase 3

Completed

• Conditions: Traumatic Brain Injury; Fatigue; Cognitive Impairment; COVID-19
• Interventions: Drug: Somatropin

• Registration Number: NCT03554265
• Lead Sponsor: The University of Texas Medical Branch, Galveston

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.

Study Timeline

• Study First Submitted: 2018-04-09
• Study First Submitted QC: 2018-05-30
• Study First Posted: 2018-06-13
• Study Start: 2018-08-06
• Primary Completion: 2023-10-04
• Study Completion: 2023-10-04
• Status Verified: 2024-01
• Last Update Submitted: 2024-01-18
• Last Update Posted: 2024-01-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 83

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
mTBI subjects	Somatropin	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
PASC subjects	Somatropin	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

Primary Outcome Measures

Name	Time	Method
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.
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 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

Name	Time	Method
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.

Trial Locations

Locations (1)

University of Texas Medical Branch; 🇺🇸 Galveston, Texas, United States