DYNamic Assessment of Multi Organ Level Dysfunction in Patients Recovering From Covid-19
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 31
- 试验地点
- 1
- 主要终点
- Resting state brain structural measures - white matter microstructure
研究概览
简要总结
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.
详细描述
Purpose and design Covid-19 manifests as a spectrum of multi-organ damage and dysfunction. Skeletal muscle wasting and strength loss from heightened inflammatory burden and hospital immobilisation, together with vascular dysfunction and lung damage, combine to create a profound insult resulting in severe deconditioning and long-lasting functional insufficiencies. Marked physiological deficits likely prevail due to the multi-organ nature of this insult, but clear understanding of breadth and magnitude is lacking.
Whilst susceptible groups exist, patients surviving this critical illness also include those who were previously fit and well, many of younger and working age, but a unifying trait is the inability to mount a dynamic physiological response to simple every-day activities, such as walking. Greater effort to address the multi-organ nature of this lack of physiological resilience is urgently warranted, it is essential to understand the relative regional contribution of the disease to pathophysiology and frailty. Further, understanding the dynamic response across organs will be fundamental in developing optimal interventions to facilitate recovery.
This project will combine state-of-the-art, validated techniques and research expertise in human physiology, MRI/MRS and clinical medicine to provide novel insight of the impact of Covid-19 on physiological resilience at a multi-organ level (here, muscle, heart and brain related to fatigue/physical activity), using exercise as a stressor. This will provide a unique clinically valuable perspective of whole body dysfunction that will underpin global rehabilitative programmes designed to maximise patient recovery and functionality.
The urgent priority to define Covid-19 multi-organ damage and optimise the rehabilitation package underpins the rapidity of this call.
There are other multi-organ MRI projects post Covid-19 (for example coverscan and C-More) which will take cohorts of patients. DYNAMO differs as it has been developed specifically to mechanistically study the cause for the persisting symptoms such as fatigue, atrophy, impaired exercise tolerance, poor vascular and metabolic health, and cognitive impairment and delineate the targets for rehabilitation. Detailed whole-body and organ level metabolic and physiological assessments will be collected using dynamic magnetic resonance imaging (MRI) and MR spectroscopy measures, with exercise as a stressor, only under stress will some deficits become apparent. This is highly novel, and will deliver unprecedented insight into the mechanisms driving persisting symptoms. DYNAMO will complement other projects, and the objectives and detailed physiological phenotyping described in DYNAMO is not covered elsewhere in other funded imaging studies. Moreover, DYNAMO will provide an important evidence-based foundation for optimising future rehabilitation.
研究设计
- 研究类型
- Observational
- 观察模型
- Other
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
- •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.
排除标准
- •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
结局指标
主要结局
Resting state brain structural measures - white matter microstructure
时间窗: 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.
Resting state myocellular fat content
时间窗: 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.
Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral oxygen extraction
时间窗: 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.
Resting state cardiac structural integrity - cardiac fibrosis
时间窗: 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.
Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral perfusion
时间窗: 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.
Muscle mRNA
时间窗: 5-7 months post hospital discharge for patients
Muscle mRNA expression will be determined in skeletal muscle samples obtained from a micro biopsy of the vastus laterals 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.
Whole body glucose disposal - glucose and insulin concentrations
时间窗: 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.
Resting state whole-body fat and muscle volumes
时间窗: 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.
Whole body glucose disposal - resting energy expenditure
时间窗: 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.
Resting state brain structural measures - white matter and grey matter volumes
时间窗: 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.
Resting state cardiac structural integrity - cardiac output
时间窗: 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.
Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cardiac output
时间窗: 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.
Motor unit size
时间窗: 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.
Dynamic changes in cerebral haemodynamics during low level supine in-bore exercise - cerebral blood flow
时间窗: 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.
Recovery kinetics of skeletal muscle phosphocreatine
时间窗: 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.
次要结局
- hand grip strength(5-7 months post hospital discharge for patients)
- Short Physical performance battery test (SPPB)(5-7 months post hospital discharge for patients)
- Clinical and demographic data(5-7 months post hospital discharge for patients)
- muscle strength and function(5-7 months post hospital discharge for patients)
- Physical activity(5-7 months post hospital discharge for patients)
- blood biomarkers for cardiac function(5-7 months post hospital discharge for patients)
- blood biomarkers for liver function(5-7 months post hospital discharge for patients)
- blood biomarkers for skeletal muscle function(5-7 months post hospital discharge for patients)
- questionnaires for quality of life and symptoms(5-7 months post hospital discharge for patients)
- blood biomarkers for inflammation(5-7 months post hospital discharge for patients)
- blood biomarkers for renal function(5-7 months post hospital discharge for patients)
- blood biomarkers for diabetes(5-7 months post hospital discharge for patients)