VasoconstrictionEarly Phase 1NCT03972683
Role of Acetylcholine in Blood Flow Regulation in Healthy Adults: Effects of Age and Exercise Training
A Early Phase 1 study testing Handgrip Exercise Training, Acetylcholine and Adenosine Triphosphate in people with Vasoconstriction and Vasodilation, run by Colorado State University at 1 site in United States.
Trial summary
The overall goal of this study is to address fundamental questions regarding how the molecule acetylcholine interacts with the sympathetic nervous system to regulate blood flow and oxygen delivery to working skeletal muscle in young and older adults. Read more about this study
- Who is it for?
- Ages 18 to 85 yearsHealthy volunteers can take part
- Conditions the study is for
- Vasoconstriction, Vasodilation
- What is being tested?
- Handgrip Exercise Training, Acetylcholine and Adenosine Triphosphate
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- 1 siteUnited States
- Study dates
- 16 Apr 2019to 31 Jul 2021
- Phase
- Early Phase 1
- 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 85 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- age 18-35 OR 60-85
Who cannot join
- recent history of smoking
- body mass index greater than 30
- history of cardiovascular or metabolic disease, including hypertension or diabetes
- medications that may affect outcome measures, such as blood pressure medications or hormone replacement therapy
- high levels of exercise training, particularly with the forearm (such as weightlifting or rock-climbing)
Trial locations and contacts
1 site in 1 country.
United States1 site
Colorado State University
Fort Collins, Colorado, 80523
About this study
Official title: Novel Role of Acetylcholine in Regulating Vascular Tone: Effects of Age and Exercise Training
The overall goal of this study is to address fundamental questions regarding how the molecule acetylcholine interacts with the sympathetic nervous system to regulate blood flow and oxygen delivery to working skeletal muscle in young and older adults. With advancing age, blood vessels supplying active muscle lose their ability to override sympathetic constriction, which limits delivery of oxygen and results in fatigue. Findings from these studies will serve as the foundation for new strategies to improve regional blood flow regulation in older adults and clinical populations, which will increase quality of life and help to preserve functional independence.
Read the detailed description
The ability of blood vessels to dilate is essential to ensure adequate blood flow and oxygen delivery to active muscle during exercise. With advancing age, exercising muscle loses the ability to overcome vasoconstriction from the sympathetic nervous system, which impairs blood flow and limits exercise tolerance. Thus, understanding the signaling mechanisms that underlie the ability of active muscle to limit sympathetic vasoconstriction will advance our understanding of blood flow regulation in humans and lay the foundation for new strategies to improve blood flow and exercise tolerance in aging and clinical populations.
Therefore, the purpose of this research is to investigate endogenous acetylcholine as an important signaling molecule that regulates blood flow during exercise. The studies will also determine whether a reduced contribution of acetylcholine explains blood flow impairments in older adults. Since exercise training is known to improve acetylcholine signaling, this research will also address whether a handgrip exercise training intervention will improve blood flow regulation. The expected outcomes will provide new insight to the basic physiology underlying vascular control in humans. Furthermore, the findings will provide insight to the age-related decline in blood flow regulation during exercise and will assess the use of an exercise intervention to improve functional outcomes in older individuals.
Participants will be asked to complete several study visits over the course of 8 weeks. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University for a 3 hour visit to assess forearm exercise capacity. In a separate 5 hour visit following an overnight fast, a physician will place a catheter in the brachial artery of the non-dominant arm to assess vascular function. Participants will then complete 7 weeks of handgrip exercise training (four sessions per week) and return to the laboratory for follow-up visits to assess forearm exercise capacity and vascular function.
- Conditions
- Vasoconstriction, Vasodilation
- Being tested
- Handgrip Exercise Training, Acetylcholine, Adenosine Triphosphate, Atropine, Phenylephrine
- Keywords
- Exercise
- Medical subject headings
- Aneurysm, Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Handgrip Exercise TrainingOther
Signaling mechanisms that regulate blood flow will be studied before and after 7 weeks of handgrip exercise training with the non-dominant forearm. Training sessions will consist of 30 min of rhythmic contractions using a handgrip exercise device, and participants will complete four training sessions per week.
AcetylcholineDrug
Also called ACh
Vasodilatory sensitivity to acetylcholine will be assessed in dose-response fashion as a standard test of vascular function. Doses of 0.5, 1.5, and 15 μg/dl forearm volume/min will be infused via a brachial artery catheter for 4 min per dose.
Adenosine TriphosphateDrug
Also called ATP
Vasodilatory sensitivity to adenosine triphosphate will be assessed during infusion of a dose of 10 μg/dl forearm volume/min administered via a brachial artery catheter over a total of 4 min.
AtropineDrug
Also called Atropine Sulfate
Atropine will be used to inhibit muscarinic acetylcholine receptors in order to determine the contribution of acetylcholine to vasodilation during exercise. An initial dose of 0.2 mg will be infused via a brachial artery catheter over 3 min, then a maintenance dose of 0.067 mg will be infused over 1 min prior to each of 5 subsequent experimental trials.
PhenylephrineDrug
Also called Phenylephrine Hydrochloride
Vasoconstriction to phenylephrine will be used to assess sensitivity to alpha 1 adrenergic stimulation. Phenylephrine will be infused via a brachial artery catheter at 0.125 or 0.25 μg/dl forearm volume/min (18-35 and 60-85 age groups, respectively), adjusted according to forearm blood flow, for a total of 16 min.
Sodium NitroprussideDrug
Also called SNP
Sodium nitroprusside will be infused via a brachial artery catheter as a control vasodilator to elevate resting forearm blood flow to a level similar to that during exercise. The dose will be adjusted to match forearm blood flow to a similar level as during handgrip exercise, with an anticipated average dose of 1 μg/dl forearm volume/min. The dose will be infused for a total of 14 min.
| Study group | Role | What they receive |
|---|---|---|
| Handgrip Exercise Training Intervention | Experimental | Participants will visit the lab for baseline measurements designed to evaluate signaling mechanisms that regulate blood flow. A physician will place a catheter in the brachial artery for pharmacological infusions. The following drugs will be administered to each participant: acetylcholine, adenosine triphosphate, atropine, phenylephrine, and sodium nitroprusside (see Interventions for further details regarding each drug). The order of infusions will be randomized and blood flow will be allowed to return to baseline between each infusion (~15 min) with the exception of atropine, which will be administered last owing to its longer half-life.
Following baseline measurements, participants will complete a 7 week handgrip exercise training intervention, then they will return to the laboratory for post-training measurements. The post-training assessments will be performed in the same manner as the baseline visit; thus, the same drugs will be infused as described above. Receives: Other: Handgrip Exercise Training; Drug: Acetylcholine; Drug: Adenosine Triphosphate; Drug: Atropine; Drug: Phenylephrine; Drug: Sodium Nitroprusside |
What is being measured
The primary outcome is the main question the study is designed to answer.
Functional sympatholysis
Change in sensitivity to phenylephrine during handgrip exercise compared to rest
Measured: Baseline (week 0) and post-intervention (week 8)
Secondary outcomes (1)
Flow-mediated dilation
Change in brachial artery diameter in response to increased shear rate
Measured: Baseline (week 0), mid-intervention (week 4), and post-intervention (week 8)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2019
- Study start16 Apr 2019
- Primary completion31 Jul 2021 (estimated)
- Study completion31 Jul 2021 (estimated)
Why it stopped: no participants enrolled
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for VasoconstrictionStudies of the same condition, open and under way.
- 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
- Early Phase 1
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- All participants will be studied before and after a handgrip exercise training intervention.
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Colorado State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Frank Dinenno, Colorado State University
- Investigators
- Frank Dinenno, PhD, Principal investigator, Colorado State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03972683
- Sponsor's protocol ID
- ACh sympatholysis
- Status last verified
- Jul 2021
- First submitted
- 31 May 2019
- Last updated
- 2 Aug 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Novel Role of Acetylcholine in Regulating Vascular Tone: Effects of Age and Exercise Training
- ClinicalTrials.gov ID
- NCT03972683
- Acronym / sponsor ID
- ACh sympatholysis
- Conditions
- Vasoconstriction, Vasodilation
- Keywords
- Exercise
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: no participants enrolled
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Colorado State UniversityUniversity, hospital or other
- Study start
- 16 Apr 2019 (actual)
- Primary completion
- 31 Jul 2021 (estimated)
- Study completion
- 31 Jul 2021 (estimated)
- First posted
- 4 Jun 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.
The overall goal of this study is to address fundamental questions regarding how the molecule acetylcholine interacts with the sympathetic nervous system to regulate blood flow and oxygen delivery to working skeletal muscle in young and older adults. With advancing age, blood vessels supplying active muscle lose their ability to override sympathetic constriction, which limits delivery of oxygen and results in fatigue. Findings from these studies will serve as the foundation for new strategies to improve regional blood flow regulation in older adults and clinical populations, which will increase quality of life and help to preserve functional independence.
Detailed description
The ability of blood vessels to dilate is essential to ensure adequate blood flow and oxygen delivery to active muscle during exercise. With advancing age, exercising muscle loses the ability to overcome vasoconstriction from the sympathetic nervous system, which impairs blood flow and limits exercise tolerance. Thus, understanding the signaling mechanisms that underlie the ability of active muscle to limit sympathetic vasoconstriction will advance our understanding of blood flow regulation in humans and lay the foundation for new strategies to improve blood flow and exercise tolerance in aging and clinical populations.
Therefore, the purpose of this research is to investigate endogenous acetylcholine as an important signaling molecule that regulates blood flow during exercise. The studies will also determine whether a reduced contribution of acetylcholine explains blood flow impairments in older adults. Since exercise training is known to improve acetylcholine signaling, this research will also address whether a handgrip exercise training intervention will improve blood flow regulation. The expected outcomes will provide new insight to the basic physiology underlying vascular control in humans. Furthermore, the findings will provide insight to the age-related decline in blood flow regulation during exercise and will assess the use of an exercise intervention to improve functional outcomes in older individuals.
Participants will be asked to complete several study visits over the course of 8 weeks. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University for a 3 hour visit to assess forearm exercise capacity. In a separate 5 hour visit following an overnight fast, a physician will place a catheter in the brachial artery of the non-dominant arm to assess vascular function. Participants will then complete 7 weeks of handgrip exercise training (four sessions per week) and return to the laboratory for follow-up visits to assess forearm exercise capacity and vascular function.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- All participants will be studied before and after a handgrip exercise training intervention.
| Arm | Type | Receives |
|---|---|---|
| Handgrip Exercise Training Intervention | Experimental | Other: Handgrip Exercise Training, Drug: Acetylcholine, Drug: Adenosine Triphosphate, Drug: Atropine, Drug: Phenylephrine, Drug: Sodium NitroprussideParticipants will visit the lab for baseline measurements designed to evaluate signaling mechanisms that regulate blood flow. A physician will place a catheter in the brachial artery for pharmacological infusions. The following drugs will be administered to each participant: acetylcholine, adenosine triphosphate, atropine, phenylephrine, and sodium nitroprusside (see Interventions for further details regarding each drug). The order of infusions will be randomized and blood flow will be allowed to return to baseline between each infusion (~15 min) with the exception of atropine, which will be administered last owing to its longer half-life. Following baseline measurements, participants will complete a 7 week handgrip exercise training intervention, then they will return to the laboratory for post-training measurements. The post-training assessments will be performed in the same manner as the baseline visit; thus, the same drugs will be infused as described above. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- age 18-35 OR 60-85
Key exclusion criteria (5 listed)
- recent history of smoking
- body mass index greater than 30
- history of cardiovascular or metabolic disease, including hypertension or diabetes
- medications that may affect outcome measures, such as blood pressure medications or hormone replacement therapy
- high levels of exercise training, particularly with the forearm (such as weightlifting or rock-climbing)
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 |
|---|---|---|
| Handgrip Exercise TrainingSignaling mechanisms that regulate blood flow will be studied before and after 7 weeks of handgrip exercise training with the non-dominant forearm. Training sessions will consist of 30 min of rhythmic contractions using a handgrip exercise device, and participants will complete four training sessions per week. | Other | Handgrip Exercise Training Intervention |
| AcetylcholineAlso: AChVasodilatory sensitivity to acetylcholine will be assessed in dose-response fashion as a standard test of vascular function. Doses of 0.5, 1.5, and 15 μg/dl forearm volume/min will be infused via a brachial artery catheter for 4 min per dose. | Drug | Handgrip Exercise Training Intervention |
| Adenosine TriphosphateAlso: ATPVasodilatory sensitivity to adenosine triphosphate will be assessed during infusion of a dose of 10 μg/dl forearm volume/min administered via a brachial artery catheter over a total of 4 min. | Drug | Handgrip Exercise Training Intervention |
| AtropineAlso: Atropine SulfateAtropine will be used to inhibit muscarinic acetylcholine receptors in order to determine the contribution of acetylcholine to vasodilation during exercise. An initial dose of 0.2 mg will be infused via a brachial artery catheter over 3 min, then a maintenance dose of 0.067 mg will be infused over 1 min prior to each of 5 subsequent experimental trials. | Drug | Handgrip Exercise Training Intervention |
| PhenylephrineAlso: Phenylephrine HydrochlorideVasoconstriction to phenylephrine will be used to assess sensitivity to alpha 1 adrenergic stimulation. Phenylephrine will be infused via a brachial artery catheter at 0.125 or 0.25 μg/dl forearm volume/min (18-35 and 60-85 age groups, respectively), adjusted according to forearm blood flow, for a total of 16 min. | Drug | Handgrip Exercise Training Intervention |
| Sodium NitroprussideAlso: SNPSodium nitroprusside will be infused via a brachial artery catheter as a control vasodilator to elevate resting forearm blood flow to a level similar to that during exercise. The dose will be adjusted to match forearm blood flow to a similar level as during handgrip exercise, with an anticipated average dose of 1 μg/dl forearm volume/min. The dose will be infused for a total of 14 min. | Drug | Handgrip Exercise Training Intervention |
Primary outcome
Functional sympatholysis
Time frame: Baseline (week 0) and post-intervention (week 8)
Change in sensitivity to phenylephrine during handgrip exercise compared to rest
1 secondary outcome
Flow-mediated dilation
Time frame: Baseline (week 0), mid-intervention (week 4), and post-intervention (week 8)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2021.
- 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. This study is not recruiting at the moment.
Frank Dinenno, PhD principal investigator
Colorado State University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Handgrip Exercise Training, Acetylcholine and Adenosine Triphosphate in people with Vasoconstriction and Vasodilation, run by Colorado State University 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 1 inclusion and 5 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: withdrawn, as of the sponsor's last update on 2 Aug 2021. 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.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
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?
Functional sympatholysis (time frame: Baseline (week 0) and post-intervention (week 8)). 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 2 Aug 2021.