Clinical trial NCT05373043: Long-term COVID and Rehabilitation
Official title: Evaluating the Long-term Health Consequences of COVID-19 and Rehabilitation Therapies to Speed Convalescence
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Long-COVID
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2022-05-13
Enrollment: 300
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Aim 1: Participants will be either long-COVID (n=40), COVID recovered (n=40), or Controls who never had COVID (n=40) and testing will take place at baseline, months 3 and 6, and every 6 months thereafter until the end of year 4. Peripheral and cerebral vascular endothelial function, along with neurocognitive testing, pulmonary function, physical function, and quality of life, will be assessed at baseline, months 3 and 6, and then every 6 months for four years.

Aim 2: Participants will be either long-COVID (n=60), COVID-recovered (n=60), or Controls who avoided COVID (n=60) as defined in Aim 1. Participants will be assigned to the Exercise+Placebo or Exercise+Mito-Q rehabilitation interventions using block randomization (block size 10). This will provide equal sample sizes (n=30) per intervention for each group.
Primary purpose: TREATMENT

Brief summary: The proposed focuses on improving both morbidity and mortality in older Veterans and those recovering from COVID-19 by developing rehabilitation therapies to augment vascular endothelial function by combating the oxidative stress and inflammation associated with aging and further induced by COVID-19. The investigators expected outcomes will have an important positive impact because they will provide scientifically sound recommendations for rehabilitation to improve vascular endothelial function and minimize the long-term consequences of COVID-19.

Detailed description: COVID-19 induces profound vascular endothelial dysfunction, the long-term impact of which is unknown.

Moreover, recovery from COVID-19 is delayed in a substantial number of COVID-19 patients (\~ 30-40%) and characterized by persistent symptoms of fatigue, weakness, and neurocognitive deficits commonly referred to as "long-COVID". The overall objective of this project is to evaluate the long-term consequences of COVID-19 in older Veterans and provide scientifically sound recommendations for vascular endothelial function-based rehabilitation in older Veterans after COVID-19 and older Veterans in general. The central hypothesis is that, given the fundamental role of oxidative stress and inflammation in long-COVID, vascular endothelial dysfunction following COVID-19 will be associated with long-term negative impacts on health and exercise-based rehabilitation with mitochondria-targeted antioxidant (Mito-Q) supplementation will synergistically improve peripheral and cerebral vascular endothelial dysfunction in older Veterans while convalescing from COVID-19. The rationale for this project is that improving COVID-19-induced vascular endothelial dysfunction by decreasing oxidative stress and inflammation with optimized rehabilitation has the potential to improve health in Veterans with long-COVID, and improve both morbidity and mortality in older Veterans. The central hypothesis will be tested by pursuing two Specific Aims: 1) determine the time course and health risks of vascular endothelial dysfunction in older Veterans with long-COVID, older Veterans who are COVID-recovered, and older Veterans who never had COVID and 2) determine the efficacy of exercise-based rehabilitation with and without Mito-Q supplementation to improve vascular endothelial function in older Veterans with long-COVID, older Veterans who are COVID-recovered, and older Veterans who never had COVID. Under Specific Aim 1, single passive leg movement (sPLM), flow-mediated dilation (FMD), and the breath-hold acceleration index (BHAI) will be used to evaluate microvascular, conduit artery, and cerebral vascular endothelial function in older patients twice annually for 4 years to determine long-term impact of COVID-19 on vascular endothelial function. Additionally, patient health risks, negative outcomes, \[neurocognitive function, and pulmonary function\] will be tracked during this time to determine the prognostic ability of the peripheral and cerebral vascular endothelial function assessments. For Specific Aim 2, microvascular (sPLM), conduit artery (FMD), and cerebral (BHAI) vascular endothelial function will be assessed before and after either exercise-based rehabilitation or exercise-based rehabilitation combined with Mito-Q supplementation to determine their efficacy to improve peripheral and cerebral vascular endothelial function in COVID-impacted Veterans and older Veterans in general. The research proposed in this application is innovative because it focuses on lead therapeutic candidates to rehabilitate peripheral and cerebral vascular endothelial function by combatting the underlying issue of a sustained elevation in oxidative stress and inflammation associated with aging and further impacted by COVID-19. The proposed research is significant because it is expected to provide scientifically sound recommendations for rehabilitation to improve health in older Veterans and those struggling to recover from COVID-19.

Eligibility criteria: Inclusion Criteria:

* 50 years of age or greater
* Long-COVID and COVID-recovered patients must have SARS-CoV-19 positive test near the time of COVID-19 diagnosis
* Long-COVID and COVID-recovered patients must be 3-12 months post-initial COVID-19 diagnosis
* Ability to sign informed consent

Exclusion Criteria:

* BMI \>45 kg/m2
* Unstable (\<6 months) or severe coronary artery disease (CAD-RADS score = 4A), peripheral artery disease (Ankle Brachial Index \<0.40), cerebrovascular disease (identified by previous stroke in last 12 months), severe COPD (=Stage III), uncontrolled hypertension (\>160/100 mmHg), chronic kidney disease requiring dialysis, severe renal insufficiency (creatinine clearance \<30 by the Cockcroft-Gault formula), Alzheimer's disease, dementia
* Orthopedic limitations that would prohibit exercise
* \[Current smokers and individuals that stopped smoking in the last 10 years\]
* Already taking Mito-Q or unwilling to cease dietary supplements for participation
* Any other condition or event considered exclusionary by the PIs or a physician

Primary outcomes:
measure: Change in Flow Mediated Dilation (FMD)
timeFrame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
measure: Change in Microvascular Function with passive leg movement (PLM)
timeFrame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
measure: Change in Cerebral Vascular Endothelial Function with Breath Hold Acceleration Index (BHAI)
timeFrame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
Secondary outcomes:
Other outcomes:
Locations:
city: Salt Lake City
country: United States
facility: VA Salt Lake City Health Care System, Salt Lake City, UT
state: Utah
Study officials:
affiliation: VA Salt Lake City Health Care System, Salt Lake City, UT
name: Joel Douglas Trinity, PhD
role: PRINCIPAL_INVESTIGATOR
References: