Receptor BlockadeEarly Phase 1NCT03738943
Pyridoxine, P2 Receptor Antagonism, and ATP-mediated Vasodilation in Young Adults
A Early Phase 1 study testing Adenosine Triphosphate, Acetylcholine and Sodium Nitroprusside in people with Receptor Blockade, run by Colorado State University at 1 site in United States.
Trial summary
Previous research has identified adenosine triphosphate (ATP) as an important vasodilator that is released from red blood cells during exercise and exposure to hypoxic environments in adult humans. Read more about this study
- Who is it for?
- Ages 18 to 30 yearsHealthy volunteers can take part
- Conditions the study is for
- Receptor Blockade
- What is being tested?
- Adenosine Triphosphate, Acetylcholine and Sodium Nitroprusside
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Feb 2019to 1 Jun 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 30 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Sedentary-moderately active
- Free of chronic disease
Who cannot join
- Current smoker
- BMI > 29.9 kg/m2
- Blood pressure equal to or greater than 140/90 mmHg
- Use of any medications including vitamin B6 supplements or antioxidants
Trial locations and contacts
1 site in 1 country.
United States1 site
Human Performance and Clinical Research Laboratory
Fort Collins, Colorado, 80523
About this study
Previous research has identified adenosine triphosphate (ATP) as an important vasodilator that is released from red blood cells during exercise and exposure to hypoxic environments in adult humans. Further, older adults appear to have lower blood flow during both of these stressors and also have lower amounts of ATP released from their red blood cells. However, the contribution of ATP to vasodilation in response to exercise and hypoxia is currently unknown due to the lack of an effective ATP receptor antagonist. We aim to determine whether Vitamin B6 or its metabolite, Pyridoxal-5-Phosphate (PLP) is an effective ATP receptor antagonist.
Read the detailed description
Adenosine triphosphate (ATP) is an established vasodilator that is released from red blood cells during a variety of stimuli including exercise and exposure to hypoxic environments. Many studies have shown that infusion of ATP can lead to vasodilation similar to that which is achieved during exercise, and that plasma ATP concentrations increase in a graded fashion during graded exercise. Further, older adults have lower levels of blood flow during exercise and hypoxia compared to their younger counterparts, and the reduced blood flow is coupled with impaired release of ATP from red blood cells during these stimuli. Thus, ATP is believed to be an important vasodilator. However, the role of ATP in the regulation of blood flow is not fully understood due to the lack of an effective ATP receptor (P2Y2) antagonist. Development of an effective P2Y2 antagonist will allow researchers to determine the role of ATP in vasodilation to stimuli such as exercise by comparing blood flow during exercise with and without the blocker. Preliminary data from our laboratory suggests that Vitamin B6 (pyridoxine hydrochloride) or its metabolite Pyridoxal-5-Phosphate (PLP) may be an effective blocker of ATP-mediated vasodilation. As a result, the purpose of this study is to determine whether Vitamin B6 or PLP can inhibit vasodilation in response to intra-arterial infusions of ATP. This study also aims to determine the specificity of Vitamin B6 or PLP by measuring its effect on vasodilation in response to infusion of several other vasodilators.
Participants will be asked to complete one screening visit and one study visit. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University following an overnight fast. A physician will then place a catheter in the brachial artery of the non-dominant arm, and participants will be randomized into one of three study arms to determine which drugs will be infused into the artery. Each arm includes ATP and two other vasodilators. The study will begin by measuring vasodilation in response to four standard doses of each vasodilator. Vasodilation in response to the vasodilators will then be assessed again following infusion of Vitamin B6 or PLP. Reduced vasodilation to any of the drugs during the second trial will suggest that Vitamin B6 or PLP is an antagonist to the channel through which the drug signals. Each study visit will last approximately 4-5 hours.
- Conditions
- Receptor Blockade
- Being tested
- Adenosine Triphosphate, Acetylcholine, Sodium Nitroprusside, Adenosine Diphosphate, Adenosine Monophosphate
- Keywords
- Adenosine Triphosphate, Pyridoxine, Cardiovascular, PLP, P5P
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Adenosine TriphosphateDrug
Also called ATP
See arm/group descriptions
AcetylcholineDrug
Also called Ach
See arm/group descriptions
Sodium NitroprussideDrug
Also called SNP
See arm/group descriptions
Adenosine DiphosphateDrug
Also called ADP
See arm/group descriptions
Adenosine MonophosphateDrug
Also called AMP
See arm/group descriptions
Uridine TriphosphateDrug
Also called UTP
See arm/group descriptions
AdenosineDrug
Also called Adenocard
See arm/group descriptions
Vitamin B 6Drug
Also called Pyridoxine, Pyridoxine Hydrochloride
See arm/group descriptions
Pyridoxal 5'-PhosphateDrug
Also called PLP, P5P, pyridoxal phosphate monohydrate, MC-1
See arm/group descriptions
| Study group | Role | What they receive |
|---|---|---|
| ATP, Ach, SNP | Experimental | All drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose.
Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each.
Acetylcholine: 1, 4, 8, and 16 μg/dl forearm volume/min for 3 minutes each.
Sodium Nitroprusside: 0.25, 0.5, 1, and 2 μg/dl forearm volume/min for 3 minutes each.
Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol.
Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. Receives: Drug: Adenosine Triphosphate; Drug: Acetylcholine; Drug: Sodium Nitroprusside; Drug: Vitamin B 6; Drug: Pyridoxal 5'-Phosphate |
| ATP, ADP, AMP | Experimental | All drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose.
Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each.
Adenosine Diphosphate: 20, 40, 80, and 160 μg/dl forearm volume/min for 3 minutes each.
Adenosine Monophosphate: 25, 50, 100, and 200 μg/dl forearm volume/min for 3 minutes each.
Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol.
Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. Receives: Drug: Adenosine Triphosphate; Drug: Adenosine Diphosphate; Drug: Adenosine Monophosphate; Drug: Vitamin B 6; Drug: Pyridoxal 5'-Phosphate |
| ATP, UTP, Adenosine | Experimental | All drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose.
Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each.
Uridine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each.
Adenosine: 3.125, 6.25, 12.5, and 25 μg/dl forearm volume/min for 3 minutes each.
Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol.
Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. Receives: Drug: Adenosine Triphosphate; Drug: Uridine Triphosphate; Drug: Adenosine; Drug: Vitamin B 6; Drug: Pyridoxal 5'-Phosphate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Vascular Conductance
Vascular conductance is an index of vascular tone through which vasodilation can be determined. Vascular conductance is calculated by measuring blood flow in response to infusion of a vasodilator and accounting for blood pressure. Thus, the change in blood flow is due to a change in vascular conductance.
Measured: Continuous measurement of vascular conductance during the 12 minute dose response for each drug. Measures are repeated following administration of Vitamin B6 or PLP.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Nov 2018
- Study start7 Feb 2019
- Primary completion1 Jun 2021
- Study completion1 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Receptor BlockadeStudies 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
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be assigned to one of three arms of the study. The arms of the study are based on the vasodilators being tested in order to determine the effect of pyridoxine or PLP on vasodilation in response to intra-arterial administration of the vasodilators.
- Masking
- None (open label)
- Enrolment
- 9 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
- NCT03738943
- Sponsor's protocol ID
- 17-7430H
- Status last verified
- Jul 2021
- First submitted
- 8 Nov 2018
- Last updated
- 27 Jul 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 27 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pyridoxine, P2 Receptor Antagonism, and ATP-mediated Vasodilation in Young Adults
- ClinicalTrials.gov ID
- NCT03738943
- Acronym / sponsor ID
- 17-7430H
- Conditions
- Receptor Blockade
- Keywords
- Adenosine Triphosphate, Pyridoxine, Cardiovascular, PLP, P5P
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 9 participants (actual)
- Lead sponsor
- Colorado State UniversityUniversity, hospital or other
- Study start
- 7 Feb 2019 (actual)
- Primary completion
- 1 Jun 2021 (actual)
- Study completion
- 1 Jun 2021 (actual)
- First posted
- 13 Nov 2018 (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.
Previous research has identified adenosine triphosphate (ATP) as an important vasodilator that is released from red blood cells during exercise and exposure to hypoxic environments in adult humans. Further, older adults appear to have lower blood flow during both of these stressors and also have lower amounts of ATP released from their red blood cells. However, the contribution of ATP to vasodilation in response to exercise and hypoxia is currently unknown due to the lack of an effective ATP receptor antagonist. We aim to determine whether Vitamin B6 or its metabolite, Pyridoxal-5-Phosphate (PLP) is an effective ATP receptor antagonist.
Detailed description
Adenosine triphosphate (ATP) is an established vasodilator that is released from red blood cells during a variety of stimuli including exercise and exposure to hypoxic environments. Many studies have shown that infusion of ATP can lead to vasodilation similar to that which is achieved during exercise, and that plasma ATP concentrations increase in a graded fashion during graded exercise. Further, older adults have lower levels of blood flow during exercise and hypoxia compared to their younger counterparts, and the reduced blood flow is coupled with impaired release of ATP from red blood cells during these stimuli. Thus, ATP is believed to be an important vasodilator. However, the role of ATP in the regulation of blood flow is not fully understood due to the lack of an effective ATP receptor (P2Y2) antagonist. Development of an effective P2Y2 antagonist will allow researchers to determine the role of ATP in vasodilation to stimuli such as exercise by comparing blood flow during exercise with and without the blocker. Preliminary data from our laboratory suggests that Vitamin B6 (pyridoxine hydrochloride) or its metabolite Pyridoxal-5-Phosphate (PLP) may be an effective blocker of ATP-mediated vasodilation. As a result, the purpose of this study is to determine whether Vitamin B6 or PLP can inhibit vasodilation in response to intra-arterial infusions of ATP. This study also aims to determine the specificity of Vitamin B6 or PLP by measuring its effect on vasodilation in response to infusion of several other vasodilators.
Participants will be asked to complete one screening visit and one study visit. Once study eligibility has been determined, participants will report to the Human Performance Clinical Research Laboratory at Colorado State University following an overnight fast. A physician will then place a catheter in the brachial artery of the non-dominant arm, and participants will be randomized into one of three study arms to determine which drugs will be infused into the artery. Each arm includes ATP and two other vasodilators. The study will begin by measuring vasodilation in response to four standard doses of each vasodilator. Vasodilation in response to the vasodilators will then be assessed again following infusion of Vitamin B6 or PLP. Reduced vasodilation to any of the drugs during the second trial will suggest that Vitamin B6 or PLP is an antagonist to the channel through which the drug signals. Each study visit will last approximately 4-5 hours.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- Participants will be assigned to one of three arms of the study. The arms of the study are based on the vasodilators being tested in order to determine the effect of pyridoxine or PLP on vasodilation in response to intra-arterial administration of the vasodilators.
| Arm | Type | Receives |
|---|---|---|
| ATP, Ach, SNP | Experimental | Drug: Adenosine Triphosphate, Drug: Acetylcholine, Drug: Sodium Nitroprusside, Drug: Vitamin B 6, Drug: Pyridoxal 5'-PhosphateAll drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose. Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each. Acetylcholine: 1, 4, 8, and 16 μg/dl forearm volume/min for 3 minutes each. Sodium Nitroprusside: 0.25, 0.5, 1, and 2 μg/dl forearm volume/min for 3 minutes each. Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol. Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. |
| ATP, ADP, AMP | Experimental | Drug: Adenosine Triphosphate, Drug: Adenosine Diphosphate, Drug: Adenosine Monophosphate, Drug: Vitamin B 6, Drug: Pyridoxal 5'-PhosphateAll drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose. Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each. Adenosine Diphosphate: 20, 40, 80, and 160 μg/dl forearm volume/min for 3 minutes each. Adenosine Monophosphate: 25, 50, 100, and 200 μg/dl forearm volume/min for 3 minutes each. Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol. Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. |
| ATP, UTP, Adenosine | Experimental | Drug: Adenosine Triphosphate, Drug: Uridine Triphosphate, Drug: Adenosine, Drug: Vitamin B 6, Drug: Pyridoxal 5'-PhosphateAll drugs will be administered via intra-arterial (brachial artery) infusion, and the dosages below will be administered two times: once before administration of Vitamin B6 (pyridoxine) and once following administration of the Vitamin B6 (pyridoxine) loading dose. Adenosine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each. Uridine Triphosphate: 1.25, 2.5, 5, and 10 μg/dl forearm volume/min for 3 minutes each. Adenosine: 3.125, 6.25, 12.5, and 25 μg/dl forearm volume/min for 3 minutes each. Vitamin B6 (pyridoxine): up to 200 mg of pyridoxine will be infused over 20 minutes. A maintenance dose of 2.5 mg/min may be used throughout the remainder of the protocol. Pyridoxal-5-Phosphate (PLP) may be used as an alternative blocker instead of pyridoxine. It will be infused at doses up to 200 µg/dl forearm volume/min. |
Who may qualify
- Ages
- 18 to 30 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Sedentary-moderately active
- Free of chronic disease
Key exclusion criteria (4 listed)
- Current smoker
- BMI > 29.9 kg/m2
- Blood pressure equal to or greater than 140/90 mmHg
- Use of any medications including vitamin B6 supplements or antioxidants
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 |
|---|---|---|
| Adenosine TriphosphateAlso: ATPSee arm/group descriptions | Drug | ATP, ADP, AMP, ATP, Ach, SNP, ATP, UTP, Adenosine |
| AcetylcholineAlso: AchSee arm/group descriptions | Drug | ATP, Ach, SNP |
| Sodium NitroprussideAlso: SNPSee arm/group descriptions | Drug | ATP, Ach, SNP |
| Adenosine DiphosphateAlso: ADPSee arm/group descriptions | Drug | ATP, ADP, AMP |
| Adenosine MonophosphateAlso: AMPSee arm/group descriptions | Drug | ATP, ADP, AMP |
| Uridine TriphosphateAlso: UTPSee arm/group descriptions | Drug | ATP, UTP, Adenosine |
| AdenosineAlso: AdenocardSee arm/group descriptions | Drug | ATP, UTP, Adenosine |
| Vitamin B 6Also: Pyridoxine, Pyridoxine HydrochlorideSee arm/group descriptions | Drug | ATP, ADP, AMP, ATP, Ach, SNP, ATP, UTP, Adenosine |
| Pyridoxal 5'-PhosphateAlso: PLP, P5P, pyridoxal phosphate monohydrate, MC-1See arm/group descriptions | Drug | ATP, ADP, AMP, ATP, Ach, SNP, ATP, UTP, Adenosine |
Primary outcome
Vascular Conductance
Time frame: Continuous measurement of vascular conductance during the 12 minute dose response for each drug. Measures are repeated following administration of Vitamin B6 or PLP.
Vascular conductance is an index of vascular tone through which vasodilation can be determined. Vascular conductance is calculated by measuring blood flow in response to infusion of a vasodilator and accounting for blood pressure. Thus, the change in blood flow is due to a change in vascular conductance.
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 27 Jul 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 Adenosine Triphosphate, Acetylcholine and Sodium Nitroprusside in people with Receptor Blockade, 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 2 inclusion and 4 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 27 Jul 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 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?
Vascular Conductance (time frame: Continuous measurement of vascular conductance during the 12 minute dose response for each drug. Measures are repeated following administration of Vitamin B6 or PLP.). 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 27 Jul 2021.