We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

DYNamic Assessment of Multi Organ Level Dysfunction in Patients Recovering From Covid-19 (DYNAMOCovid-19)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05060497
Recruitment Status : Recruiting
First Posted : September 29, 2021
Last Update Posted : September 29, 2021
Sponsor:
Information provided by (Responsible Party):
University of Nottingham

Brief Summary:
In this study the investigators are hoping to the find out what changes occur within the body of people recovering from Covid-19 at 5-7 months and 11-13 months following discharge from hospital, compared to healthy controls, and whether these changes can help explain why some patients may experience fatigue. Measurements will be taken using state-of-the-art MRI imaging at rest and also during low intensity exercise, to mimic everyday activity. In doing so it is expected that this will inform ways to adapt exercise rehabilitation programmes, making them better suited for Covid-19 survivors.

Condition or disease
Covid19

Show Show detailed description

Layout table for study information
Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: DYNamic Assessment of Multi Organ Level Dysfunction in Patients Recovering From Covid-19
Actual Study Start Date : October 27, 2020
Estimated Primary Completion Date : January 31, 2022
Estimated Study Completion Date : August 31, 2022

Resource links provided by the National Library of Medicine


Group/Cohort
Covid patients
Participants who were treated in hospital with laboratory diagnosed Covid-19 requiring high flow oxygen, non invasive ventilation or intubation and have now recovered. They will be recruited 5-7 months post discharge from their local hospital Trust
Healthy control volunteers
Participants who are otherwise healthy, who have not had Covid-19 infection and are age, gender, BMI and ethnicity matched to patients



Primary Outcome Measures :
  1. Resting state brain structural measures - white matter and grey matter volumes [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MRI sequences to assess grey matter and white matter volume in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  2. Resting state brain structural measures - white matter microstructure [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MRI sequences to assess white matter tract distribution in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  3. Resting state cardiac structural integrity - cardiac output [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MRI sequences to assess cardiac output at rest in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  4. Resting state cardiac structural integrity - cardiac fibrosis [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MRI sequences to look for the degree of fibrosis at rest in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  5. Resting state whole-body fat and muscle volumes [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MRI sequence (mDixon) to assess whole-body fat and muscle content in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  6. Resting state myocellular fat content [ Time Frame: 5-7 months post hospital discharge for patients ]
    Use of MR spectroscopy sequence to assess intramyocellular and extramyocellular lipid content in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  7. Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral blood flow [ Time Frame: 5-7 months post hospital discharge for patients ]
    MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral blood flow in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  8. Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral perfusion [ Time Frame: 5-7 months post hospital discharge for patients ]
    MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral perfusion in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  9. Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral oxygen extraction [ Time Frame: 5-7 months post hospital discharge for patients ]
    MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cerebral oxygen extraction in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  10. Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cardiac output [ Time Frame: 5-7 months post hospital discharge for patients ]
    MRI sequences will be carried out at rest, during steady-state low level in-bore supine exercise and recovery to assess changes in cardiac output in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  11. Recovery kinetics of skeletal muscle phosphocreatine [ Time Frame: 5-7 months post hospital discharge for patients ]
    Recovery kinetics of phosphocreatine (Pcr) in the gastrocnemius will be measured following its depletion using MR spectroscopy to assess skeletal muscle quality in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  12. Muscle mitochondrial content [ Time Frame: 5-7 months post hospital discharge for patients ]
    Citrate synthetase activity will be measured in skeletal muscle samples obtained from a micro biopsy of the vastus laterals to assess mitochondrial content in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  13. Whole body glucose disposal - glucose and insulin concentrations [ Time Frame: 5-7 months post hospital discharge for patients ]
    Oral glucose tolerance test will be used to measure glucose and insulin concentration for whole body glucose disposal in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  14. Whole body glucose disposal - resting energy expenditure [ Time Frame: 5-7 months post hospital discharge for patients ]
    Indirect calorimetry will be used to measure resting energy expenditure for whole body glucose disposal in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.

  15. Motor unit size [ Time Frame: 5-7 months post hospital discharge for patients ]
    Intramuscular electromyography will be used to measure motor unit size in the vastus lateralis in patients with severe Covid-19 at 5-7 months and 11-13 months of discharge from hospital as well as non-Covid, age, gender, BMI and ethnicity matched volunteers.


Secondary Outcome Measures :
  1. Clinical and demographic data [ Time Frame: 5-7 months post hospital discharge for patients ]
    age, ethnicity, covid related hospital stay (for patients), covid related interventions (for patients), comorbidities, medications list

  2. muscle strength and function [ Time Frame: 5-7 months post hospital discharge for patients ]
    quadriceps maximum voluntary contraction using cybex dynamometer

  3. hand grip strength [ Time Frame: 5-7 months post hospital discharge for patients ]
    hand grip strength using a hand grip dynamometer will be measured

  4. Short Physical performance battery test (SPPB) [ Time Frame: 5-7 months post hospital discharge for patients ]
    SPPB will be used to assess gait speed, balance and ability to sit up from a chair. Scores within the domains will add up to 4 with 0 being the minimum score

  5. Physical activity [ Time Frame: 5-7 months post hospital discharge for patients ]
    Measuring step count using Sensewear activity arm band

  6. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Fatigue severity score - min score 7 max score 63

  7. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Quality of life as judged by SF-36 - min score 0 max score 100

  8. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Dyspnoea-12 - min score 0 max score 36

  9. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Nottingham activities of daily living - min score 0 max score 22

  10. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Mental health assessed by personal health questionnaire - min score 0 max score 27

  11. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    MoCA cognition level - min score 0 max score 30

  12. questionnaires for quality of life and symptoms [ Time Frame: 5-7 months post hospital discharge for patients ]
    Frailty as judged by Rockwood CFS - min score 1 max score 9

  13. blood biomarkers for cardiac function [ Time Frame: 5-7 months post hospital discharge for patients ]
    concentration of troponin

  14. blood biomarkers for cardiac function [ Time Frame: 5-7 months post hospital discharge for patients ]
    concentration of brain natriuretic peptide

  15. blood biomarkers for renal function [ Time Frame: 5-7 months post hospital discharge for patients ]
    calculated glomerular filtration rate

  16. blood biomarkers for liver function [ Time Frame: 5-7 months post hospital discharge for patients ]
    concentration of alanine transaminase

  17. blood biomarkers for skeletal muscle function [ Time Frame: 5-7 months post hospital discharge for patients ]
    concentration of creatine kinase

  18. blood biomarkers for inflammation [ Time Frame: 5-7 months post hospital discharge for patients ]
    concentration of cytokines such as TNF alpha, IL-6 and C-reactive peptide

  19. blood biomarkers for diabetes [ Time Frame: 5-7 months post hospital discharge for patients ]
    Measurement of HbA1c


Biospecimen Retention:   Samples Without DNA

Blood samples: Full blood count, renal function including eGFR, troponin, brain natriuretic peptide, glycosylated haemoglobin, liver function, ferritin, creatine kinase (CK), clotting and international normalized ratio (INR), TNF-alpha, IL-6 and CRP

Muscle biopsy: citrate synthetase



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
recruiting 30 patients and 10 controls
Criteria

Inclusion Criteria:

Covid patients -

  • Adults aged 18 years and over,
  • Severe, laboratory confirmed Covid-19 infection that required hospital admission,
  • 5-7 months post discharge from local hospital Trusts.

Controls -

  • No active or previous Covid infection, ie no previous positive Covid PCR test and absence of active symptoms
  • Matched for age, gender, BMI and ethnicity.

Exclusion Criteria:

  • Absolute contraindications for MR scan
  • Pre-Covid diagnosed chronic respiratory, renal, cardiovascular or cerebrovascular disease or diabetes
  • BMI<20kg/m2
  • Pregnancy
  • Those requiring oxygen therapy or non-invasive ventilation
  • Those on anticoagulation will be included but will not have a muscle biopsy
  • Active arthritis
  • Overt muscle damage, e.g. plasma creatine kinase > 300
  • Any other conditions in addition to the above that the investigators consider may affect study measurements or safety

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05060497


Contacts
Layout table for location contacts
Contact: Ayushman Gupta, MBChB, MRCPUK 01158231702 ayushman.gupta@nottingham.ac.uk

Locations
Layout table for location information
United Kingdom
NIHR Nottingham BRC Respiratory Theme, University of Nottingham and NUH Trust Recruiting
Nottingham, Nottinghamshire, United Kingdom, NG5 1PB
Contact: Ayushman Gupta    01158231702    mszag4@exmail.nottingham.ac.uk   
Sponsors and Collaborators
University of Nottingham
Investigators
Layout table for investigator information
Principal Investigator: Charlotte E Bolton, Prof NIHR Nottingham Biomedical Research Centre, Respiratory theme
Publications:

Layout table for additonal information
Responsible Party: University of Nottingham
ClinicalTrials.gov Identifier: NCT05060497    
Other Study ID Numbers: 20050
First Posted: September 29, 2021    Key Record Dates
Last Update Posted: September 29, 2021
Last Verified: September 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
COVID-19
Respiratory Tract Infections
Infections
Pneumonia, Viral
Pneumonia
Virus Diseases
Coronavirus Infections
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Lung Diseases
Respiratory Tract Diseases