Long-COVIDNCT05373043
Long-term COVID and Rehabilitation
A study testing Mitoquinone in people with Long-COVID, run by VA Office of Research and Development at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Long-COVID
- What is being tested?
- Mitoquinone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Nov 2022to 31 Oct 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
VA Salt Lake City Health Care System, Salt Lake City, UT
Salt Lake City, Utah, 84148-0001
P Jon White, MD, (801) 582-1565 ext. 4897, Paul.White2@va.gov
Joel Douglas Trinity, PhD
About this study
Official title: Evaluating the Long-term Health Consequences of COVID-19 and Rehabilitation Therapies to Speed Convalescence
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.
Read the 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.
- Conditions
- Long-COVID
- Being tested
- Mitoquinone, Placebo
- Medical subject headings
- Post-Acute COVID-19 Syndrome
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MitoquinoneDietary supplement
Also called MitoQ
Mito-Q is a supplement that targets mitochondrial function. Linking a triphenyl-phosphonium cation to coenzyme-Q, to produce Mito-Q, results in a lipophilic compound, which, due to the large mitochondrial membrane potential, selectively accumulates within mitochondria. This targeted antioxidant approach results in 50- to 100-fold more Mito-Q accumulation compared to non-targeted antioxidant delivery.
PlaceboDietary supplement
A placebo will be used in combination with exercise rehabilitation allowing for a double blinded placebo controlled design.
| Study group | Role | What they receive |
|---|---|---|
| Exercise Rehabilitation | Experimental | Participants will be assigned to the Exercise+Placebo or Exercise+Mito-Q rehabilitation interventions using block randomization (block size 10). Receives: Dietary Supplement: Mitoquinone |
| Exercise Rehabilitation with Placebo | Placebo comparator | Participants will be assigned to Exercise+Placebo rehabilitation using block randomization (block size 10) Receives: Dietary Supplement: Mitoquinone; Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Flow Mediated Dilation (FMD)
FMD will be quantified as the peak diameter measured post-cuff release and expressed as a percent change from the baseline diameter. Higher FMD indicates better vascular function and greater change over time suggests improvement.
Measured: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
Change in Microvascular Function with passive leg movement (PLM)
The PLM leg blood flow response will be characterized by the area under the curve over 45 seconds, accounting for baseline. Higher PLM indicates better vascular function and greater change over time suggests improvement.
Measured: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
Change in Cerebral Vascular Endothelial Function with Breath Hold Acceleration Index (BHAI)
BHAI will be determined by fitting a linear regression to the most linear portion of the change in middle cerebral artery blood velocity over time during the breath-hold maneuver. Higher BHAI indicates better vascular function and greater change over time suggests improvement.
Measured: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 May 2022
- Study start1 Nov 2022
- Primary completion31 Oct 2027 (estimated)
- Study completion31 Oct 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Long-COVIDStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- 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.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Joel Douglas Trinity, PhD, Principal investigator, VA Salt Lake City Health Care System, Salt Lake City, UT
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05373043
- Sponsor's protocol ID
- F3810-R
- Other IDs
- RX003810
- Status last verified
- Jul 2026
- First submitted
- 12 May 2022
- Last updated
- 30 Jul 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evaluating the Long-term Health Consequences of COVID-19 and Rehabilitation Therapies to Speed Convalescence
- ClinicalTrials.gov ID
- NCT05373043
- Acronym / sponsor ID
- F3810-R
- Conditions
- Long-COVID
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- 1 Nov 2022 (actual)
- Primary completion
- 31 Oct 2027 (estimated)
- Study completion
- 31 Oct 2028 (estimated)
- First posted
- 13 May 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- 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.
| Arm | Type | Receives |
|---|---|---|
| Exercise Rehabilitation | Experimental | Dietary Supplement: MitoquinoneParticipants will be assigned to the Exercise+Placebo or Exercise+Mito-Q rehabilitation interventions using block randomization (block size 10). |
| Exercise Rehabilitation with Placebo | Placebo comparator | Dietary Supplement: Mitoquinone, Dietary Supplement: PlaceboParticipants will be assigned to Exercise+Placebo rehabilitation using block randomization (block size 10) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MitoquinoneAlso: MitoQMito-Q is a supplement that targets mitochondrial function. Linking a triphenyl-phosphonium cation to coenzyme-Q, to produce Mito-Q, results in a lipophilic compound, which, due to the large mitochondrial membrane potential, selectively accumulates within mitochondria. This targeted antioxidant approach results in 50- to 100-fold more Mito-Q accumulation compared to non-targeted antioxidant delivery. | Dietary supplement | Exercise Rehabilitation, Exercise Rehabilitation with Placebo |
| PlaceboA placebo will be used in combination with exercise rehabilitation allowing for a double blinded placebo controlled design. | Dietary supplement | Exercise Rehabilitation with Placebo |
Primary outcome
Change in Flow Mediated Dilation (FMD)
Time frame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
FMD will be quantified as the peak diameter measured post-cuff release and expressed as a percent change from the baseline diameter. Higher FMD indicates better vascular function and greater change over time suggests improvement.
Change in Microvascular Function with passive leg movement (PLM)
Time frame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
The PLM leg blood flow response will be characterized by the area under the curve over 45 seconds, accounting for baseline. Higher PLM indicates better vascular function and greater change over time suggests improvement.
Change in Cerebral Vascular Endothelial Function with Breath Hold Acceleration Index (BHAI)
Time frame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.
BHAI will be determined by fitting a linear regression to the most linear portion of the change in middle cerebral artery blood velocity over time during the breath-hold maneuver. Higher BHAI indicates better vascular function and greater change over time suggests improvement.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2026.
- 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.
Joel Douglas Trinity, PhD principal investigator
VA Salt Lake City Health Care System, Salt Lake City, UT
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Mitoquinone in people with Long-COVID, run by VA Office of Research and Development 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 3 inclusion and 6 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: looking for participants now, as of the sponsor's last update on 30 Jul 2026. 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. Some participants in this study may receive a placebo. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Joel D Trinity, PhD ((801) 582-1565 ext. 1199, Joel.Trinity@va.gov), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Flow Mediated Dilation (FMD) (time frame: Baseline, months 3 and 6, and every 6 months thereafter until the end of year 4.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 30 Jul 2026.