Covid19NCT04860869
Endocrine, Metabolic and Microbiome Influence on the Post-acute Sequelae SARS-CoV-2 (PASC)
An observational study of Covid19, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
Trial summary
The aim of this study is characterize the endocrine, metabolic and microbiomes of patients with post-acute sequelae SARS-CoV-2 infection (PASC) and patients that have recovered from COVID without lingering symptoms. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Covid19
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 12 May 2021to 31 May 2022
- Phase
- Observational
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 1. Subjects recovered from COVID without lingering symptoms (nPASC) 2. Subjects with post-COVID syndrome (PASC)
Who may be able to join
- Male or female with a history of COVID with diagnosis confirmed by PCR test.
- Minimum of 6 months since diagnosis of COVID by PCR test.
- Ages 18 to 80 years.
- Participant is willing and able to give informed consent for participation in the study.
- Male or female with a history of COVID with diagnosis confirmed by PCR test.
- Has been seen at UTMB Post COVID clinic.
Show all 10Show fewer
- Minimum of 6 months since diagnosis of COVID by PCR test.
- Ages 18 to 80 years.
- Score of 3 or higher on any question 1-3 of the Brief Fatigue Inventory (BFI) questionnaire.
- Participant is willing and able to give informed consent for participation in the study.
Who cannot join
- Current COVID infection.
- Unable to walk unassisted.
- Significant heart, liver, kidney, blood or respiratory disease as determined by Principal Investigator.
- Uncontrolled diabetes mellitus.
- Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
- Current alcohol or drug abuse.
Show all 21Show fewer
- History of psychosis.
- Pregnancy or become pregnant during the trial.
- Subjects who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.
- Other medical condition or medication administration deemed exclusionary by the study investigators.
- COVID Symptomatic Subjects (PASC)
- Current COVID infection.
- Unable to walk unassisted.
- Significant heart, liver, kidney, blood or respiratory disease.
- Uncontrolled diabetes mellitus.
- Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
- Current alcohol or drug abuse.
- History of psychosis.
- Pregnancy or become pregnant during the trial.
- Subjects who are being managed with narcotics will be excluded as the effects of central nervous system depressants may interfere with study test results.
- Other medical condition or medication administration deemed exclusionary by the study investigators.
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Texas Medical Branch
Galveston, Texas, 77555
About this study
The aim of this study is characterize the endocrine, metabolic and microbiomes of patients with post-acute sequelae SARS-CoV-2 infection (PASC) and patients that have recovered from COVID without lingering symptoms.
Read the detailed description
The onset of the COVID-19 pandemic has led to a subset of patients that, once recovered from the acute infection, also experience an intractable and debilitating set of lingering symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC). The most common symptoms include anxiety, shortness of breath, continued loss of the sense of smell and taste, loss of appetite with subsequent weight loss, sleep difficulties, severe fatigue, cognitive dysfunction (foggy brain) and increased frailty. These patients frequently present to the emergency room looking for symptom management because they are unable to perform normal activities of daily living and maintain job performance. Thus, it is critical to characterize the baseline endocrine, metabolic, inflammatory and microbiome alterations in the post-COVID syndrome patients to better identify and manage the symptoms to prevent potential long-term health consequences.
University of Texas Medical Branch (UTMB) has established a post-COVID clinic for management of these patients, but it is recognized that a more complete clinical picture of the underlying mechanisms driving these lingering symptoms is needed.
Persistent and long-lasting health problems are common in patients after COVID-19 infection. In a recent study of patients that had been hospitalized with COVID-19, two months after discharge, 87% reported at least one lingering symptom (joint pain, fatigue, breathing issues, etc), more than 50% reported more than three lingering issues, and over 40% reported a reduction in their of quality of life. Another study found that at 1-month after hospitalization for COVID-19, 74% reported persistent issues related to shortness of breath and a decrease in both physical and mental health. Preliminary data from the UTMB Post-COVID Recovery clinic agree with these two recent reports. In a recent study, 1 1/2 months after COVID-19 diagnosis, patients reported on average 10 of the 18 common symptoms (with 90% having chest pain, 87% dyspnea, 75% fatigue, and 90% with cognitive changes). While the previous studies examined patients that had severe COVID-19 infections, >50% of the patients were never hospitalized, yet have numerous persistent symptoms. This has serious implications for the ability of patients to return to work, downstream effects on mental health due to sometimes drastic lifestyle and work capacity changes, and the ability to engage in activities or hobbies enjoyed prior to COVID-19 illness.
Notably, the cluster of symptoms associated with PASC include profound fatigue and cognitive dysfunction, which are strikingly consistent with a syndrome that the investigators clinical research team has described in patients after traumatic brain injury (TBI) designated Brain Injury Associated Fatigue and Altered Cognition (BIAFAC). Over the last 12 months the investigators have reported the characteristics of BIAFAC syndrome. In particular, TBI patients with BIAFAC present with lingering and profoundly debilitating symptoms including severe fatigue, cognitive dysfunction (foggy brain), sleep disturbances, and the inability to perform activities of daily living that persist for years post-injury. Mechanistically the investigators have explored the role of the gut microbiome discovering altered communities in TBI patients in long-term care facilities compared with controls. The investigators also established that many TBI patients with BIAFAC also present with abnormal growth hormone (GH) secretion, and when treated with recombinant GH, a majority of patients have significant improvement of both fatigue and impaired cognition. While studies are underway to understand the details of the mechanism causing BIAFAC and why GH treatment alleviates symptoms in these patients, the investigators are intrigued that the symptom phenotype with PASC patients overlaps with many BIAFAC symptoms. It is possible that PASC may be addressed through similar treatment strategies including the potential for prebiotic/probiotic enhancement of microbiome health.
In the current pilot proposal, the investigators will characterize the baseline endocrine, metabolic, inflammatory and gut microbiome alterations in PASC patients and patients who recovered without lingering symptoms from COVID infection. These patients will be compared to the investigators extensive database of BIAFAC patients and normal controls. From this critical baseline data, the investigators will develop carefully defined clinical research trials that will test potential treatments for alleviating the syndrome. The investigators hypothesize that an imbalanced endocrine axis stemming from COVID-19 infection leads to metabolic, inflammatory and microbial dysregulation resulting in the onset of persistent post-COVID symptoms.
Specific Aims
Specific Aim 1: Characterize the baseline physiological measures of endocrine function, metabolism, inflammation, and composition of the gut and nasal microbiome of patients reporting symptoms of PASC.
Specific Aim 2: Assess baseline neuropsychological measures of fatigue, sleep, and cognition for patients reporting symptoms of PASC.
Specific Aim 3: Correlate physiological and neuropsychological measures of PASC and compare those measures to the investigators extensive database of BIAFAC patients and normal controls.
Specific Aim 4: Characterize the microbiome of patients with PASC and compare to: a)our database of healthy control subjects, b) our database of symptomatic BIAFAC patients, c) new collected samples of patients with a history of COVID who did not develop PASC.
- Conditions
- Covid19
- Keywords
- cognitive impairment, fatigue
- Medical subject headings
- COVID-19, Cognitive Dysfunction, Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| symptomatic post-acute sequelae SARS-CoV-2 (PASC) | Patients with post-acute sequelae SARS-CoV-2 (PASC) after COVID-19 infection | |
| non-symptomatic post-COVID | Patients with that recovered without lingering symptoms after being infected with COVID |
What is being measured
The primary outcome is the main question the study is designed to answer.
Insulin-Like Growth Factor-1 (IGF1)
Insulin-Like Growth Factor-1 (IGF1) will be measured in serum. Results will be reported in ng/mL.
Measured: baseline
Follicle Stimulating Hormone (FSH)
Follicle Stimulation Hormone (FSH) will be measured in serum.
Measured: baseline
Sex Hormone Binding Globulin (SHBG)
Sex Hormone Binding Globulin (SHBG) will be measured in serum. Results will be reported in nmol/L.
Measured: baseline
Total Testosterone
Total testosterone will be measured in serum of male subjects. Results will be reported in ng/dL.
Measured: baseline
Free Testosterone
Free testosterone will be measured in serum of male subjects. Results will be reported in pg/mL.
Measured: baseline
Prolactin
Prolactin will be measured in serum. Results will be reported in ng/mL.
Measured: baseline
Thyroid Stimulating Hormone (TSH)
Thyroid Stimulating Hormone (TSH) will be measured in serum. Results will be reported in mUI/L.
Measured: baseline
C Reactive Protein (CRP)
C Reactive Protein (CRP) will be measured in serum.
Measured: baseline
Vitamin B12
Vitamin B12 will be measured in serum.
Measured: baseline
Vitamin D 25OH
Vitamin D 25OH will be measured in serum.
Measured: baseline
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Glucose will be measured in serum before (0 minutes) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Measured: Before glucose consumption
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Glucose will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Measured: 120 minutes after glucose consumption
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Insulin will be measured in serum before (0 min) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Measured: Before glucose consumption
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Insulin will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Measured: 120 minutes after glucose consumption
Glucose Derived CO2 as Measured by Breath During the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Glucose derived CO2 will be measured in breath samples at 120 minutes after oral consumption of 75g glucose isotopically labeled with 150 mg [U-13C6] glucose.
Glucose-derived breath CO2 data are analyzed by measuring the ratios of 13CO2 to 12CO2 in single breath samples using an UBiT-IR300 infrared spectrophotometer (Otsuka Electronics, Hirakata, Osaka, Japan). The UBIT-IR300 calculates the difference in 13CO2 abundance from the baseline breath sample to each timed sample and expresses this as per mille delta over baseline (%DOB).
OGTT will be performed on PASC subjects only.
Measured: 120 minutes after glucose consumption
Sleep Quality as Measured by Pittsburgh Sleep Quality Index
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.
Measured: baseline
Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of human growth hormone. 1 mg glucagon (for subjects over 90 kg, 1.5 mg glucagon) will be injected intramuscularly (IM) in the deltoid muscle of the subject and blood will be drawn at specified time points.
Results will be reported as ng/mL.
Measured: Before glucagon administration
Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at time point 90 minutes after glucagon injection to test for levels of human growth hormone.
Results will be reported as ng/mL.
Measured: 90 minutes after glucagon administration
Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 120 minutes after glucagon injection to test for levels of growth hormone.
Results will be reported as ng/mL.
Measured: 120 minutes after glucagon administration
Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 150 minutes after glucagon injection to test for levels of growth hormone.
Results will be reported as ng/mL.
Measured: 150 minutes after glucagon administration
Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 180 minutes after glucagon injection to test for levels of growth hormone.
Results will be reported as ng/mL.
Measured: 180 minutes after glucagon administration
Basal Metabolic Rate as Measured by Resting Energy Expenditure
Resting Energy Expenditure will be measured by capturing the expired breath of subjects while at rest with a metabolic cart over a 30 minute time period. Data from the first 5 minutes will be discarded and the remaining 25 minutes of data will be averaged to calculate the resting energy expenditure. Data will be reported as kilocalories/day
Procedure will be performed on PASC subjects only.
Measured: baseline
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) Before Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of cortisol. 0.25 mg Cortrosyn will be administered and additional serum (3.5 mL) will be collected at specified time points.
Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Measured: Before Cortrosyn administration
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 30 Minutes After Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 30 minutes after Cortrosyn administration to test for levels of cortisol. Procedure will be performed on PASC subjects only.
Results will be reported as ug/dL.
Measured: 30 minutes after Cortrosyn administration
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 60 Minutes After Cortrosyn Administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 60 minutes after Cortrosyn administration to test for levels of cortisol.
Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Measured: 60 minutes after Cortrosyn administration
Cognitive Function as Measured by Montreal Cognitive Assessment
The Montreal Cognitive Assessment (MoCA) will be used to assess cognition.
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. Scores range from 0 to 30, higher score being a better outcome.
Measured: baseline
Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale
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 average of the scores for all 15 items is regarded as the GSRS total score. A higher score indicates a worse outcome.
Measured: baseline
Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory
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.
Measured: baseline
Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults
Symptoms of growth hormone deficiency will be measured 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.
Measured: baseline
Depression Measured by the Beck Depression Inventory-II
The Beck Depression Inventory- II (BDI-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.
Measured: baseline
Secondary outcomes (1)
Free T4
Free T4 measured at baseline
Measured: baseline
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Apr 2021
- Study start12 May 2021
- Primary completion31 May 2022
- Study completion31 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Covid19Studies of the same condition, open and under way.
- More trials run by The University of Texas Medical Branch, GalvestonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Randall Urban, MD, Principal investigator, University of Texas
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04860869
- Sponsor's protocol ID
- 20-0361
- Status last verified
- Aug 2024
- First submitted
- 3 Mar 2021
- Last updated
- 28 Oct 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2024 Jan 1;579:112071. doi: 10.1016/j.mce.2023.112071. Epub 2023 Oct 8.
PubMed 37816478
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endocrine, Metabolic and Microbiome Influence on the Post-acute Sequelae SARS-CoV-2 (PASC)
- ClinicalTrials.gov ID
- NCT04860869
- Acronym / sponsor ID
- 20-0361
- Conditions
- Covid19
- Keywords
- cognitive impairment, fatigue
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- The University of Texas Medical Branch, GalvestonUniversity, hospital or other
- Study start
- 12 May 2021 (actual)
- Primary completion
- 31 May 2022 (actual)
- Study completion
- 31 May 2022 (actual)
- First posted
- 27 Apr 2021 (actual)
- Results
- Posted 28 Oct 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this study is characterize the endocrine, metabolic and microbiomes of patients with post-acute sequelae SARS-CoV-2 infection (PASC) and patients that have recovered from COVID without lingering symptoms.
Detailed description
The onset of the COVID-19 pandemic has led to a subset of patients that, once recovered from the acute infection, also experience an intractable and debilitating set of lingering symptoms termed post-acute sequelae SARS-CoV-2 infection (PASC). The most common symptoms include anxiety, shortness of breath, continued loss of the sense of smell and taste, loss of appetite with subsequent weight loss, sleep difficulties, severe fatigue, cognitive dysfunction (foggy brain) and increased frailty. These patients frequently present to the emergency room looking for symptom management because they are unable to perform normal activities of daily living and maintain job performance. Thus, it is critical to characterize the baseline endocrine, metabolic, inflammatory and microbiome alterations in the post-COVID syndrome patients to better identify and manage the symptoms to prevent potential long-term health consequences.
University of Texas Medical Branch (UTMB) has established a post-COVID clinic for management of these patients, but it is recognized that a more complete clinical picture of the underlying mechanisms driving these lingering symptoms is needed.
Persistent and long-lasting health problems are common in patients after COVID-19 infection. In a recent study of patients that had been hospitalized with COVID-19, two months after discharge, 87% reported at least one lingering symptom (joint pain, fatigue, breathing issues, etc), more than 50% reported more than three lingering issues, and over 40% reported a reduction in their of quality of life. Another study found that at 1-month after hospitalization for COVID-19, 74% reported persistent issues related to shortness of breath and a decrease in both physical and mental health. Preliminary data from the UTMB Post-COVID Recovery clinic agree with these two recent reports. In a recent study, 1 1/2 months after COVID-19 diagnosis, patients reported on average 10 of the 18 common symptoms (with 90% having chest pain, 87% dyspnea, 75% fatigue, and 90% with cognitive changes). While the previous studies examined patients that had severe COVID-19 infections, >50% of the patients were never hospitalized, yet have numerous persistent symptoms. This has serious implications for the ability of patients to return to work, downstream effects on mental health due to sometimes drastic lifestyle and work capacity changes, and the ability to engage in activities or hobbies enjoyed prior to COVID-19 illness.
Notably, the cluster of symptoms associated with PASC include profound fatigue and cognitive dysfunction, which are strikingly consistent with a syndrome that the investigators clinical research team has described in patients after traumatic brain injury (TBI) designated Brain Injury Associated Fatigue and Altered Cognition (BIAFAC). Over the last 12 months the investigators have reported the characteristics of BIAFAC syndrome. In particular, TBI patients with BIAFAC present with lingering and profoundly debilitating symptoms including severe fatigue, cognitive dysfunction (foggy brain), sleep disturbances, and the inability to perform activities of daily living that persist for years post-injury. Mechanistically the investigators have explored the role of the gut microbiome discovering altered communities in TBI patients in long-term care facilities compared with controls. The investigators also established that many TBI patients with BIAFAC also present with abnormal growth hormone (GH) secretion, and when treated with recombinant GH, a majority of patients have significant improvement of both fatigue and impaired cognition. While studies are underway to understand the details of the mechanism causing BIAFAC and why GH treatment alleviates symptoms in these patients, the investigators are intrigued that the symptom phenotype with PASC patients overlaps with many BIAFAC symptoms. It is possible that PASC may be addressed through similar treatment strategies including the potential for prebiotic/probiotic enhancement of microbiome health.
In the current pilot proposal, the investigators will characterize the baseline endocrine, metabolic, inflammatory and gut microbiome alterations in PASC patients and patients who recovered without lingering symptoms from COVID infection. These patients will be compared to the investigators extensive database of BIAFAC patients and normal controls. From this critical baseline data, the investigators will develop carefully defined clinical research trials that will test potential treatments for alleviating the syndrome. The investigators hypothesize that an imbalanced endocrine axis stemming from COVID-19 infection leads to metabolic, inflammatory and microbial dysregulation resulting in the onset of persistent post-COVID symptoms.
Specific Aims
Specific Aim 1: Characterize the baseline physiological measures of endocrine function, metabolism, inflammation, and composition of the gut and nasal microbiome of patients reporting symptoms of PASC.
Specific Aim 2: Assess baseline neuropsychological measures of fatigue, sleep, and cognition for patients reporting symptoms of PASC.
Specific Aim 3: Correlate physiological and neuropsychological measures of PASC and compare those measures to the investigators extensive database of BIAFAC patients and normal controls.
Specific Aim 4: Characterize the microbiome of patients with PASC and compare to: a)our database of healthy control subjects, b) our database of symptomatic BIAFAC patients, c) new collected samples of patients with a history of COVID who did not develop PASC.
Study design
- Observational model
- Cohort
- Time perspective
- Cross-sectional
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| symptomatic post-acute sequelae SARS-CoV-2 (PASC) | – | –Patients with post-acute sequelae SARS-CoV-2 (PASC) after COVID-19 infection |
| non-symptomatic post-COVID | – | –Patients with that recovered without lingering symptoms after being infected with COVID |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- 1. Subjects recovered from COVID without lingering symptoms (nPASC) 2. Subjects with post-COVID syndrome (PASC)
Key inclusion criteria (10 listed)
- Male or female with a history of COVID with diagnosis confirmed by PCR test.
- Minimum of 6 months since diagnosis of COVID by PCR test.
- Ages 18 to 80 years.
- Participant is willing and able to give informed consent for participation in the study.
- Male or female with a history of COVID with diagnosis confirmed by PCR test.
Key exclusion criteria (21 listed)
- Current COVID infection.
- Unable to walk unassisted.
- Significant heart, liver, kidney, blood or respiratory disease as determined by Principal Investigator.
- Uncontrolled diabetes mellitus.
- Any history of a recently (12 months) diagnosed cancer other than a skin cancer (excluding melanoma).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Insulin-Like Growth Factor-1 (IGF1)
Time frame: baseline
Insulin-Like Growth Factor-1 (IGF1) will be measured in serum. Results will be reported in ng/mL.
Follicle Stimulating Hormone (FSH)
Time frame: baseline
Follicle Stimulation Hormone (FSH) will be measured in serum.
Sex Hormone Binding Globulin (SHBG)
Time frame: baseline
Sex Hormone Binding Globulin (SHBG) will be measured in serum. Results will be reported in nmol/L.
Total Testosterone
Time frame: baseline
Total testosterone will be measured in serum of male subjects. Results will be reported in ng/dL.
Free Testosterone
Time frame: baseline
Free testosterone will be measured in serum of male subjects. Results will be reported in pg/mL.
Prolactin
Time frame: baseline
Prolactin will be measured in serum. Results will be reported in ng/mL.
Thyroid Stimulating Hormone (TSH)
Time frame: baseline
Thyroid Stimulating Hormone (TSH) will be measured in serum. Results will be reported in mUI/L.
C Reactive Protein (CRP)
Time frame: baseline
C Reactive Protein (CRP) will be measured in serum.
Vitamin B12
Time frame: baseline
Vitamin B12 will be measured in serum.
Vitamin D 25OH
Time frame: baseline
Vitamin D 25OH will be measured in serum.
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Time frame: Before glucose consumption
Glucose will be measured in serum before (0 minutes) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Glucose Tolerance as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Time frame: 120 minutes after glucose consumption
Glucose will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) Before Glucose Consumption
Time frame: Before glucose consumption
Insulin will be measured in serum before (0 min) oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Insulin as Measured by the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Time frame: 120 minutes after glucose consumption
Insulin will be measured in serum at 120 minutes after oral consumption of 75g glucose. OGTT will be performed on PASC subjects only.
Glucose Derived CO2 as Measured by Breath During the Oral Glucose Tolerance Test (OGTT) 120 Minutes After Glucose Consumption
Time frame: 120 minutes after glucose consumption
Glucose derived CO2 will be measured in breath samples at 120 minutes after oral consumption of 75g glucose isotopically labeled with 150 mg [U-13C6] glucose. Glucose-derived breath CO2 data are analyzed by measuring the ratios of 13CO2 to 12CO2 in single breath samples using an UBiT-IR300 infrared spectrophotometer (Otsuka Electronics, Hirakata, Osaka, Japan). The UBIT-IR300 calculates the difference in 13CO2 abundance from the baseline breath sample to each timed sample and expresses this as per mille delta over baseline (%DOB). OGTT will be performed on PASC subjects only.
Sleep Quality as Measured by Pittsburgh Sleep Quality Index
Time frame: 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.
Growth Hormone as Measured by Glucagon Stimulation Test Before Glucagon Administration
Time frame: Before glucagon administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of human growth hormone. 1 mg glucagon (for subjects over 90 kg, 1.5 mg glucagon) will be injected intramuscularly (IM) in the deltoid muscle of the subject and blood will be drawn at specified time points. Results will be reported as ng/mL.
Growth Hormone as Measured by Glucagon Stimulation Test 90 Minutes After Glucagon Administration
Time frame: 90 minutes after glucagon administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at time point 90 minutes after glucagon injection to test for levels of human growth hormone. Results will be reported as ng/mL.
Growth Hormone as Measured by Glucagon Stimulation Test 120 Minutes After Glucagon Administration
Time frame: 120 minutes after glucagon administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 120 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Growth Hormone as Measured by Glucagon Stimulation Test 150 Minutes After Glucagon Administration
Time frame: 150 minutes after glucagon administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 150 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Growth Hormone as Measured by Glucagon Stimulation Test 180 Minutes After Glucagon Administration
Time frame: 180 minutes after glucagon administration
Growth hormone secretion will be measured using the glucagon stimulation test. Serum will be collected at timepoint 180 minutes after glucagon injection to test for levels of growth hormone. Results will be reported as ng/mL.
Basal Metabolic Rate as Measured by Resting Energy Expenditure
Time frame: baseline
Resting Energy Expenditure will be measured by capturing the expired breath of subjects while at rest with a metabolic cart over a 30 minute time period. Data from the first 5 minutes will be discarded and the remaining 25 minutes of data will be averaged to calculate the resting energy expenditure. Data will be reported as kilocalories/day Procedure will be performed on PASC subjects only.
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) Before Cortrosyn Administration
Time frame: Before Cortrosyn administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected for the baseline (time: 0 minutes) to test for levels of cortisol. 0.25 mg Cortrosyn will be administered and additional serum (3.5 mL) will be collected at specified time points. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 30 Minutes After Cortrosyn Administration
Time frame: 30 minutes after Cortrosyn administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 30 minutes after Cortrosyn administration to test for levels of cortisol. Procedure will be performed on PASC subjects only. Results will be reported as ug/dL.
Cortisol as Measured by the Adrenocorticotropic Hormone Stimulation Test (ACTH) 60 Minutes After Cortrosyn Administration
Time frame: 60 minutes after Cortrosyn administration
Cortisol secretion will be measured using the ACTH stimulation test. Serum will be collected at time point 60 minutes after Cortrosyn administration to test for levels of cortisol. Results will be reported as ug/dL. Procedure will be performed on PASC subjects only.
Cognitive Function as Measured by Montreal Cognitive Assessment
Time frame: baseline
The Montreal Cognitive Assessment (MoCA) will be used to assess cognition. 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. Scores range from 0 to 30, higher score being a better outcome.
Gastrointestinal Health Measured by the Gastrointestinal Symptom Rating Scale
Time frame: 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 average of the scores for all 15 items is regarded as the GSRS total score. A higher score indicates a worse outcome.
Fatigue as Measured by the Multidimensional Fatigue Symptom Inventory
Time frame: 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.
Symptoms of Growth Hormone Deficiency Measured by the Questionnaire Quality of Life - Assessment of Growth Hormone Deficiency in Adults
Time frame: baseline
Symptoms of growth hormone deficiency will be measured 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.
Depression Measured by the Beck Depression Inventory-II
Time frame: baseline
The Beck Depression Inventory- II (BDI-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.
1 secondary outcome
Free T4
Time frame: baseline
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 37816478Wright TJ, Pyles RB, Sheffield-Moore M, Deer RR, Randolph KM, McGovern KA, Danesi CP, Gilkison CR, Ward WW, Vargas JA, Armstrong PA, Lindsay SE, Zaidan MF, Seashore J, Wexler TL, Masel BE, Urban RJ. Low growth hormone secretion associated with post-acute sequelae SARS-CoV-2 infection (PASC) neurologic symptoms: A case-control pilot study. Mol Cell Endocrinol. 2024 Jan 1;579:112071. doi: 10.1016/j.mce.2023.112071. Epub 2023 Oct 8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Randall Urban, MD principal investigator
University of Texas
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid19, run by The University of Texas Medical Branch, Galveston at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 28 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Insulin-Like Growth Factor-1 (IGF1) (time frame: baseline). The study lists 30 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04860869, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2024.