Vascular DiseasesNCT04200560
Autophagy Maintains Vascular Function Through a Novel Glycolysis-linked Pathway Regulating eNOS
A study testing Rhythmic Handgrip Exercise and Chronic Exercise Training in people with Vascular Diseases, run by University of Utah at 1 site in United States.
Trial summary
Aging is inevitable and is the primary risk factor for developing cardiovascular disease. The molecular mechanisms that drive vascular dysfunction in the context of aging are incompletely understood. Read more about this study
- Who is it for?
- Ages 18 to 90 yearsHealthy volunteers can take part
- Conditions the study is for
- Vascular Diseases
- What is being tested?
- Rhythmic Handgrip Exercise and Chronic Exercise Training
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jul 2018to 30 May 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 90 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Candidates must be between 18 and 90 y of age
- Candidates must be free of overt disease as assessed by a) medical history; b) standard blood chemistries (chem. 7 panel), c) ECG at rest; d) limb vascular examination (ankle-brachial BP index > 0.9); e) resting BP < 140/90 mmHg; and f) skinfold % body fat assessment.
- Subjects will have a body mass index (BMI) between 19 and 30 and have plasma glucose concentrations < 7.0 mmol/L under fasting conditions and < 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
Who cannot join
- Candidates <18 or >90 y of age
- Candidates demonstrating abnormal ECG, ankle-brachial BP index <0.9, resting BP > 140/90
- Candidates demonstrating a BMI <19 or > 30
- Candidates demonstrating plasma glucose concentrations > 7.0 mmol/L under fasting conditions and > 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
- Candidates demonstrating dyslipidemia (plasma total cholesterol > 240 mg/dl with LDL-cholesterol > 160 mg/dl)
- Candidates reporting a history of myocardial infarction, unstable cardiac ischemia, recent cardiac catheterization, carotid artery disease, transient ischemic attack
- Women taking hormone replacement therapy (HRT) currently or in the preceding year will be excluded from the proposed studies due to the direct vascular effects of HRT.
Trial locations and contacts
1 site in 1 country.
About this study
Aging is inevitable and is the primary risk factor for developing cardiovascular disease. The molecular mechanisms that drive vascular dysfunction in the context of aging are incompletely understood. The overall hypothesis is that the age-related decline in endothelial cell (EC) autophagy leads to arterial dysfunction. This study will determine whether physiological shear-stress affects autophagosome formation and nitrous oxide (NO) generation in ECs.
Read the detailed description
It is hypothesized that genetic autophagy suppression prevents shear-stress induced purinergic signaling to endothelial nitrous oxide synthase (eNOS) and this pathway will be evaluated in primary arterial ECs obtained from older adult (> 60 years) and adult (18-30 years) subjects before and following rhythmic handgrip exercise that elevates brachial artery shear-rate similarly in both groups. ECs will be used to quantify markers of EC autophagy, eNOS activation, and NO generation. The study will also determine whether exercise-training attenuates the aging-associated decline in EC autophagy, and whether intact autophagy is required for training-induced vascular improvements. To evaluate this potential, it will be determined whether one-limb rhythmic handgrip exercise training by older adult (> 60 y) human subjects is sufficient to elevate basal and shear-induced EC autophagy initiation, eNOS activation, and NO generation vs. the contralateral sedentary limb. Results from this work have tremendous potential to reveal a new therapeutic target and approach for restoring / maintaining vascular function in the aging population.
- Conditions
- Vascular Diseases
- Being tested
- Rhythmic Handgrip Exercise, Chronic Exercise Training
- Keywords
- Aging, Endothelial Cell Autophagy
- Medical subject headings
- Vascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rhythmic Handgrip ExerciseOther
60 minute rhythmic handgrip exercise
Chronic Exercise TrainingOther
Handgrip exercise training consisting of three 60-minute training sessions per week for eight weeks.
| Study group | Role | What they receive |
|---|---|---|
| Healthy Adult Subjects | Experimental | Healthy adult subjects (18 - 30 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise Receives: Other: Rhythmic Handgrip Exercise |
| Healthy Older Adult Subjects | Experimental | Healthy older adult subjects (> 60 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise and after Chronic Exercise Training. Receives: Other: Rhythmic Handgrip Exercise; Other: Chronic Exercise Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in biomarker beclin-1 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker Atg3 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker Atg5 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker Atg7 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker Lamp1 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker Lamp2 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker p62 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker beclin-1 after chronic exercise training
Measured: 8 weeks
Change in biomarker Atg3 after chronic exercise training
Measured: 8 weeks
Change in biomarker Atg5 after chronic exercise training
Measured: 8 weeks
Change in biomarker Atg7 after chronic exercise training
Measured: 8 weeks
Change in biomarker Lamp1 after chronic exercise training
Measured: 8 weeks
Change in biomarker Lamp2 after chronic exercise training
Measured: 8 weeks
Change in biomarker p62 after chronic exercise training
Measured: 8 weeks
Secondary outcomes (6)
Change in radial arterial diameter after Rhythmic Handgrip Exercise
Measured: 60 min
Change in radial arterial flow rate after Rhythmic Handgrip Exercise
Measured: 60 min
Change in biomarker p-eNOSS1177 after Rhythmic Handgrip Exercise
Measured: 60 min
Change in radial arterial diameter after chronic exercise training
Measured: 8 weeks
Change in radial arterial flow rate after chronic exercise training
Measured: 8 weeks
Change in biomarker p-eNOSS1177 after chronic exercise training
Measured: 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Dec 2019
- Study start1 Jul 2018
- Primary completion30 May 2022
- Study completion30 May 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Vascular DiseasesStudies of the same condition, open and under way.
- More trials run by University of UtahThe 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Utah
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, John David Symons, University of Utah
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04200560
- Sponsor's protocol ID
- 00077971
- Status last verified
- Aug 2022
- First submitted
- 18 Jun 2019
- Last updated
- 22 Aug 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Upon written request, a limited, de-identified, anonymized dataset will be created pursuant to the Data use Agreement. This DUA will limit use of the dataset and prohibit the recipient from taking steps to identify individuals whose data is included in the dataset. This dataset will be provided through a password-protected, machine-readable database format. Whenever possible, the dataset will be delivered through physical transfer of a storage medium.
Study at a glance
From the registry record, last updated by the sponsor on 22 Aug 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Autophagy Maintains Vascular Function Through a Novel Glycolysis-linked Pathway Regulating eNOS
- ClinicalTrials.gov ID
- NCT04200560
- Acronym / sponsor ID
- 00077971
- Conditions
- Vascular Diseases
- Keywords
- Aging, Endothelial Cell Autophagy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- University of UtahUniversity, hospital or other
- Study start
- 1 Jul 2018 (actual)
- Primary completion
- 30 May 2022 (actual)
- Study completion
- 30 May 2022 (actual)
- First posted
- 16 Dec 2019 (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.
Aging is inevitable and is the primary risk factor for developing cardiovascular disease. The molecular mechanisms that drive vascular dysfunction in the context of aging are incompletely understood. The overall hypothesis is that the age-related decline in endothelial cell (EC) autophagy leads to arterial dysfunction. This study will determine whether physiological shear-stress affects autophagosome formation and nitrous oxide (NO) generation in ECs.
Detailed description
It is hypothesized that genetic autophagy suppression prevents shear-stress induced purinergic signaling to endothelial nitrous oxide synthase (eNOS) and this pathway will be evaluated in primary arterial ECs obtained from older adult (> 60 years) and adult (18-30 years) subjects before and following rhythmic handgrip exercise that elevates brachial artery shear-rate similarly in both groups. ECs will be used to quantify markers of EC autophagy, eNOS activation, and NO generation. The study will also determine whether exercise-training attenuates the aging-associated decline in EC autophagy, and whether intact autophagy is required for training-induced vascular improvements. To evaluate this potential, it will be determined whether one-limb rhythmic handgrip exercise training by older adult (> 60 y) human subjects is sufficient to elevate basal and shear-induced EC autophagy initiation, eNOS activation, and NO generation vs. the contralateral sedentary limb. Results from this work have tremendous potential to reveal a new therapeutic target and approach for restoring / maintaining vascular function in the aging population.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Healthy Adult Subjects | Experimental | Other: Rhythmic Handgrip ExerciseHealthy adult subjects (18 - 30 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise |
| Healthy Older Adult Subjects | Experimental | Other: Rhythmic Handgrip Exercise, Other: Chronic Exercise TrainingHealthy older adult subjects (> 60 years) will be assessed for markers of EC autophagy, eNOS activation, and NO generation before and after Rhythmic Handgrip Exercise and after Chronic Exercise Training. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Candidates must be between 18 and 90 y of age
- Candidates must be free of overt disease as assessed by a) medical history; b) standard blood chemistries (chem. 7 panel), c) ECG at rest; d) limb vascular examination (ankle-brachial BP index > 0.9); e) resting BP < 140/90 mmHg; and f) skinfold % body fat assessment.
- Subjects will have a body mass index (BMI) between 19 and 30 and have plasma glucose concentrations < 7.0 mmol/L under fasting conditions and < 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
Key exclusion criteria (7 listed)
- Candidates <18 or >90 y of age
- Candidates demonstrating abnormal ECG, ankle-brachial BP index <0.9, resting BP > 140/90
- Candidates demonstrating a BMI <19 or > 30
- Candidates demonstrating plasma glucose concentrations > 7.0 mmol/L under fasting conditions and > 11.1 mmol/L at 120 minutes of an oral glucose tolerance test (OGTT)
- Candidates demonstrating dyslipidemia (plasma total cholesterol > 240 mg/dl with LDL-cholesterol > 160 mg/dl)
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 |
|---|---|---|
| Rhythmic Handgrip Exercise60 minute rhythmic handgrip exercise | Other | Healthy Adult Subjects, Healthy Older Adult Subjects |
| Chronic Exercise TrainingHandgrip exercise training consisting of three 60-minute training sessions per week for eight weeks. | Other | Healthy Older Adult Subjects |
Primary outcome
Change in biomarker beclin-1 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker Atg3 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker Atg5 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker Atg7 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker Lamp1 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker Lamp2 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker p62 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker beclin-1 after chronic exercise training
Time frame: 8 weeks
Change in biomarker Atg3 after chronic exercise training
Time frame: 8 weeks
Change in biomarker Atg5 after chronic exercise training
Time frame: 8 weeks
Change in biomarker Atg7 after chronic exercise training
Time frame: 8 weeks
Change in biomarker Lamp1 after chronic exercise training
Time frame: 8 weeks
Change in biomarker Lamp2 after chronic exercise training
Time frame: 8 weeks
Change in biomarker p62 after chronic exercise training
Time frame: 8 weeks
6 secondary outcomes
Change in radial arterial diameter after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in radial arterial flow rate after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in biomarker p-eNOSS1177 after Rhythmic Handgrip Exercise
Time frame: 60 min
Change in radial arterial diameter after chronic exercise training
Time frame: 8 weeks
Change in radial arterial flow rate after chronic exercise training
Time frame: 8 weeks
Change in biomarker p-eNOSS1177 after chronic exercise training
Time frame: 8 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Aug 2022.
- Individual participant dataSharing planned: Yes. Upon written request, a limited, de-identified, anonymized dataset will be created pursuant to the Data use Agreement. This DUA will limit use of the dataset and prohibit the recipient from taking steps to identify individuals whose data is included in the dataset. This dataset will be provided through a password-protected, machine-readable database format. Whenever possible, the dataset will be delivered through physical transfer of a storage medium.
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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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rhythmic Handgrip Exercise and Chronic Exercise Training in people with Vascular Diseases, run by University of Utah 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 7 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 22 Aug 2022. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in biomarker beclin-1 after Rhythmic Handgrip Exercise (time frame: 60 min). The study lists 14 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 22 Aug 2022.