Cardiovascular DiseasesPhase 1NCT03680573
The Effect of Antioxidants on Skin Blood Flow-BH4
A Phase 1 study testing Apocynin, Allopurinol and BH4 in people with Cardiovascular Diseases and Cardiovascular Risk Factor, run by The University of Texas at Arlington at 1 site in United States.
Trial summary
The goal of this study is to examine possible mechanisms of heightened vasoconstriction in Black/African American men and women as possible links to the elevated prevalence of cardiovascular dysfunction and disease. The main targets in this study are sources of oxidative stress Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- Conditions the study is for
- Cardiovascular Diseases, Cardiovascular Risk Factor, Vasoconstriction
- What is being tested?
- Apocynin, Allopurinol and BH4
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- 8 Jan 2018to 5 May 2018
- Phase
- 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 35 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Individuals (ages 18-35, both genders) will be recruited from the greater Arlington area to participate in the study.
- Must self-report both parents as either African American or Caucasian American.
Who cannot join
- Individuals who have donated more than 550 ml of blood within the past 8 weeks will not have blood drawn from them in this protocol. However, if they remain interested in the study, and otherwise meet the inclusion criteria, than we may still opt to proceed with data collection.
- Individuals with cardiovascular, neurological, and/or metabolic illnesses will be excluded from participating as well as individuals with a history of various diseases of the microvasculature including Reynaud's disease, cold-induced urticaria, cryoglobulinemia, etc.
- Subjects currently taking any prescription medications and individuals with a body mass index about 30 kg/m2) will be excluded.
- Pregnant subjects and children (i.e. younger than 18) will not be recruited for the study. Eligible females will be scheduled for days 2-7 of their menstrual cycle to account for hormonal effects on blood flow. A regular menstrual cycle is required to identify and schedule the study for the low hormone period, therefore females who lack a regular cycle will be excluded from the study. Females currently taking birth control are eligible, as long as they can be scheduled during a low-hormone "placebo" week. If their hormone do not contain a placebo week than these individuals will not be eligible for data collection. Females who are breast-feeding will also be eligible as there are no systemic or lasting effects of the proposed vasoactive agents.
- Given that smoking can affect the peripheral vasculature, current smokers and individuals who regularly smoked (>1 pack per two weeks) within the prior 2 years will be excluded
Trial locations and contacts
1 site in 1 country.
United States1 site
Engineering Research Building
Arlington, Texas, 76019
About this study
The goal of this study is to examine possible mechanisms of heightened vasoconstriction in Black/African American men and women as possible links to the elevated prevalence of cardiovascular dysfunction and disease. The main targets in this study are sources of oxidative stress
Read the detailed description
African Americans (AA) not only have a higher prevalence of hypertension but the severity of the cardiovascular complications related to this condition are greater in this population relative to other populations. While the underlying causes of this elevated risk are multifactorial, vascular dysfunction (i.e. impaired vasodilation and/or augmented vasoconstriction) is believed to be a key contributing factor. The investigators have recently observed (UTA IRB 2016-0268) that the small blood vessels in the skin (the cutaneous microvasculature) in AA, but otherwise healthy individuals, have an impaired blood flow response in the cutaneous circulation to local heating when compared to age, body mass index (BMI), and gender, matched Caucasians (CA). This blunted response is abolished in AA when the sites are pre-treated with either Allopurinol or Apocynin which block the production of xanthine oxidase and NADPH oxidase, respectively. In addition, Tetrahydrobiopterin (BH4) is critically involved in vascular function. BH4 is a cofactor involved in the conversion of L-Arginine into the potent vasodilator nitric oxide (NO) by the enzyme endothelial nitric oxide synthase (eNOS). Reduced bioavailable BH4 leads to elevated oxidative stress and thus impaired vascular function.
In addition to local heating another commonly utilized research approach to assess microcirculatory vascular function is via local infusion of the potent vasodilator methacholine (Mch). Mch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production. Much like the local heating data mentioned above, our laboratory (data collected while at UT Austin) has demonstrated a blunted response to Mch in AA relative to CA. However, the role of xanthine oxidase, NADPH oxidase, and BH4 in this blunted response remains unknown.
- Being tested
- Control: Lacated Ringers, Apocynin, Allopurinol, BH4, NG Nitro L Arginine Methyl Ester
- Keywords
- Racial Differences, Oxidative Stress
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control: Lacated RingersDrug
This site will serve as the control site
ApocyninDrug
This site will be used to inhibit NADPH oxidase and subsequent production of superoxide.
AllopurinolDrug
This site will be use to inhibit xanthine oxidase and subsequent production of superoxide.
BH4Drug
This site will be use to locally supplement BH4.
NG Nitro L Arginine Methyl EsterDrug
Also called L-Name
L-Name is a NOS inhibitor that is administered to each site to allow for the quantification of NO contribution to vasodilation. The infusion rate will be 2 µl/min
Sodium NitroprussideDrug
Also called SNP
SNP will be perfused through each site to induce maximal vasodilation. The infusion rate will be 2 µl/min
Acetyl-ß-methylcholine chlorideDrug
Also called Mch
Mch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production.
| Study group | Role | What they receive |
|---|---|---|
| Control- Lactated Ringers | Active comparator | This site will serve as the control site and will receive lactated Ringer's (saline solution) at an infusion rate of 2 µl/min. Receives: Drug: Control: Lacated Ringers; Drug: NG Nitro L Arginine Methyl Ester; Drug: Sodium Nitroprusside; Drug: Acetyl-ß-methylcholine chloride |
| Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone) | Experimental | This site will receive 100 µM apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone) at an infusion rate of 2 µl/min. Receives: Drug: Apocynin; Drug: NG Nitro L Arginine Methyl Ester; Drug: Sodium Nitroprusside; Drug: Acetyl-ß-methylcholine chloride |
| Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one) | Experimental | This site will receive 10 µM allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one)at an infusion rate of 2 µl/min. Receives: Drug: Allopurinol; Drug: NG Nitro L Arginine Methyl Ester; Drug: Sodium Nitroprusside; Drug: Acetyl-ß-methylcholine chloride |
| BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride) | Experimental | This site will receive 10 mM (6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride (BH4) at an infusion rate of 2 µl/min. Receives: Drug: BH4; Drug: NG Nitro L Arginine Methyl Ester; Drug: Sodium Nitroprusside; Drug: Acetyl-ß-methylcholine chloride |
What is being measured
The primary outcome is the main question the study is designed to answer.
Blood Flow Response to the Administration of Methacholine (Mch) before and after Infusions of Vasoactive Drugs using Intradermal Microdialysis and Laser Doppler Fluxmetry
To establish impaired blood flow response to local administration of Mch in African American relative to Caucasians. Mch will be administered using intradermal microdialysis in separate doses while the skin blood flux response will be determined using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of maximal flux. The role of oxidative stress and low nitric oxide synthase cofactors will be assessed using infusions of apocynin/allopurinol and tetrahydrobiopterin (BH4), respectively. These infusions will be given after the first infusion of Mch and before the second infusion of Mch to determine how Mch responsiveness changes with these vasoactive drugs.
Measured: Through study completion, an average of 1 Year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Sep 2018
- Study start8 Jan 2018
- Primary completion5 May 2018
- Study completion5 May 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies 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
- Phase 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- The University of Texas at Arlington
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Matthew Brothers, The University of Texas at Arlington
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03680573
- Sponsor's protocol ID
- 2017-0842
- Status last verified
- Sep 2018
- First submitted
- 17 Sep 2018
- Last updated
- 26 Sep 2018
- 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 26 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Antioxidants on Skin Blood Flow-BH4
- ClinicalTrials.gov ID
- NCT03680573
- Acronym / sponsor ID
- 2017-0842
- Keywords
- Racial Differences, Oxidative Stress
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- The University of Texas at ArlingtonUniversity, hospital or other
- Study start
- 8 Jan 2018 (actual)
- Primary completion
- 5 May 2018 (actual)
- Study completion
- 5 May 2018 (actual)
- First posted
- 21 Sep 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.
The goal of this study is to examine possible mechanisms of heightened vasoconstriction in Black/African American men and women as possible links to the elevated prevalence of cardiovascular dysfunction and disease. The main targets in this study are sources of oxidative stress
Detailed description
African Americans (AA) not only have a higher prevalence of hypertension but the severity of the cardiovascular complications related to this condition are greater in this population relative to other populations. While the underlying causes of this elevated risk are multifactorial, vascular dysfunction (i.e. impaired vasodilation and/or augmented vasoconstriction) is believed to be a key contributing factor. The investigators have recently observed (UTA IRB 2016-0268) that the small blood vessels in the skin (the cutaneous microvasculature) in AA, but otherwise healthy individuals, have an impaired blood flow response in the cutaneous circulation to local heating when compared to age, body mass index (BMI), and gender, matched Caucasians (CA). This blunted response is abolished in AA when the sites are pre-treated with either Allopurinol or Apocynin which block the production of xanthine oxidase and NADPH oxidase, respectively. In addition, Tetrahydrobiopterin (BH4) is critically involved in vascular function. BH4 is a cofactor involved in the conversion of L-Arginine into the potent vasodilator nitric oxide (NO) by the enzyme endothelial nitric oxide synthase (eNOS). Reduced bioavailable BH4 leads to elevated oxidative stress and thus impaired vascular function.
In addition to local heating another commonly utilized research approach to assess microcirculatory vascular function is via local infusion of the potent vasodilator methacholine (Mch). Mch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production. Much like the local heating data mentioned above, our laboratory (data collected while at UT Austin) has demonstrated a blunted response to Mch in AA relative to CA. However, the role of xanthine oxidase, NADPH oxidase, and BH4 in this blunted response remains unknown.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- Each subject has one control site and three experimental sites concurrently tested within the same study using intradermal microdialysis on the dorsal forearm.
| Arm | Type | Receives |
|---|---|---|
| Control- Lactated Ringers | Active comparator | Drug: Control: Lacated Ringers, Drug: NG Nitro L Arginine Methyl Ester, Drug: Sodium Nitroprusside, Drug: Acetyl-ß-methylcholine chlorideThis site will serve as the control site and will receive lactated Ringer's (saline solution) at an infusion rate of 2 µl/min. |
| Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone) | Experimental | Drug: Apocynin, Drug: NG Nitro L Arginine Methyl Ester, Drug: Sodium Nitroprusside, Drug: Acetyl-ß-methylcholine chlorideThis site will receive 100 µM apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone) at an infusion rate of 2 µl/min. |
| Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one) | Experimental | Drug: Allopurinol, Drug: NG Nitro L Arginine Methyl Ester, Drug: Sodium Nitroprusside, Drug: Acetyl-ß-methylcholine chlorideThis site will receive 10 µM allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one)at an infusion rate of 2 µl/min. |
| BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride) | Experimental | Drug: BH4, Drug: NG Nitro L Arginine Methyl Ester, Drug: Sodium Nitroprusside, Drug: Acetyl-ß-methylcholine chlorideThis site will receive 10 mM (6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride (BH4) at an infusion rate of 2 µl/min. |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Individuals (ages 18-35, both genders) will be recruited from the greater Arlington area to participate in the study.
- Must self-report both parents as either African American or Caucasian American.
Key exclusion criteria (5 listed)
- Individuals who have donated more than 550 ml of blood within the past 8 weeks will not have blood drawn from them in this protocol. However, if they remain interested in the study, and otherwise meet the inclusion criteria, than we may still opt to proceed with data collection.
- Individuals with cardiovascular, neurological, and/or metabolic illnesses will be excluded from participating as well as individuals with a history of various diseases of the microvasculature including Reynaud's disease, cold-induced urticaria, cryoglobulinemia, etc.
- Subjects currently taking any prescription medications and individuals with a body mass index about 30 kg/m2) will be excluded.
- Pregnant subjects and children (i.e. younger than 18) will not be recruited for the study. Eligible females will be scheduled for days 2-7 of their menstrual cycle to account for hormonal effects on blood flow. A regular menstrual cycle is required to identify and schedule the study for the low hormone period, therefore females who lack a regular cycle will be excluded from the study. Females currently taking birth control are eligible, as long as they can be scheduled during a low-hormone "placebo" week. If their hormone do not contain a placebo week than these individuals will not be eligible for data collection. Females who are breast-feeding will also be eligible as there are no systemic or lasting effects of the proposed vasoactive agents.
- Given that smoking can affect the peripheral vasculature, current smokers and individuals who regularly smoked (>1 pack per two weeks) within the prior 2 years will be excluded
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 |
|---|---|---|
| Control: Lacated RingersThis site will serve as the control site | Drug | Control- Lactated Ringers |
| ApocyninThis site will be used to inhibit NADPH oxidase and subsequent production of superoxide. | Drug | Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone) |
| AllopurinolThis site will be use to inhibit xanthine oxidase and subsequent production of superoxide. | Drug | Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one) |
| BH4This site will be use to locally supplement BH4. | Drug | BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride) |
| NG Nitro L Arginine Methyl EsterAlso: L-NameL-Name is a NOS inhibitor that is administered to each site to allow for the quantification of NO contribution to vasodilation. The infusion rate will be 2 µl/min | Drug | Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one), Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone), BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride), Control- Lactated Ringers |
| Sodium NitroprussideAlso: SNPSNP will be perfused through each site to induce maximal vasodilation. The infusion rate will be 2 µl/min | Drug | Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one), Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone), BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride), Control- Lactated Ringers |
| Acetyl-ß-methylcholine chlorideAlso: MchMch is an acetylcholine analog that causes endothelial dependent vasodilation primarily through stimulation of NO production. | Drug | Allopurinol (1H-pyrazolo[3,4-d]pyrimidin-4(2H)-one), Apocynin (1-(4-Hydroxy-3-methoxyphenyl)ethanone), BH4 ((6R)-5,6,7,8-Tetrahydrobiopterin dihydrochloride), Control- Lactated Ringers |
Primary outcome
Blood Flow Response to the Administration of Methacholine (Mch) before and after Infusions of Vasoactive Drugs using Intradermal Microdialysis and Laser Doppler Fluxmetry
Time frame: Through study completion, an average of 1 Year
To establish impaired blood flow response to local administration of Mch in African American relative to Caucasians. Mch will be administered using intradermal microdialysis in separate doses while the skin blood flux response will be determined using laser Doppler fluxmetry. All changes in flux will be normalized and reported as a percentage of maximal flux. The role of oxidative stress and low nitric oxide synthase cofactors will be assessed using infusions of apocynin/allopurinol and tetrahydrobiopterin (BH4), respectively. These infusions will be given after the first infusion of Mch and before the second infusion of Mch to determine how Mch responsiveness changes with these vasoactive drugs.
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 26 Sep 2018.
- 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.
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 Phase 1 study testing Apocynin, Allopurinol and BH4 in people with Cardiovascular Diseases and Cardiovascular Risk Factor, run by The University of Texas at Arlington 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 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: finished, as of the sponsor's last update on 26 Sep 2018. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Blood Flow Response to the Administration of Methacholine (Mch) before and after Infusions of Vasoactive Drugs using Intradermal Microdialysis and Laser Doppler Fluxmetry (time frame: Through study completion, an average of 1 Year). 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 26 Sep 2018.