Vascular Reaction to MedicationsNCT00838695
Variability in Adrenergic Response
A study testing Phenylephrine in people with Vascular Reaction to Medications, run by Vanderbilt University at 1 site in United States.
Trial summary
The goal of this project is to determine the genetic factors contributing to interindividual differences in response to physiological and pharmacological vasoconstrictors and vasodilators. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Vascular Reaction to Medications
- What is being tested?
- Phenylephrine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 106 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2009to Dec 2011
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age between 18 and 40 years, inclusive.
- Subject must be willing to give written informed consent and be able to adhere to diet and study schedules.
- Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations.
- Subjects must have a normal or clinically acceptable physical examination and ECG.
- Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator.
Who cannot join
- Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within two weeks prior to study drug administration.
- Subjects who are presently, or were formerly, narcotic addicts or alcoholics.
- Subjects who have a clinically significant allergy/intolerance to phenylephrine.
- Females with a positive serum/urine pregnancy test at screening.
- Females who are nursing.
- Subject using sildenafil or other phosphodiesterase inhibitors.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
The goal of this project is to determine the genetic factors contributing to interindividual differences in response to physiological and pharmacological vasoconstrictors and vasodilators.
Read the detailed description
The dorsal hand vein model is a relatively non-invasive and robust experimental model to examine the local in vivo effect of vasoactive drugs without elucidating systemic counterregulatory reflexes. Infusion of incremental low doses of phenylephrine into a dorsal hand vein results in increasing local venoconstriction, without systemic effects. Similarly, infusion of incremental low doses of nitroglycerin into a preconstricted dorsal hand vein results in increasing local venodilation, without systemic effects. Systemic vascular responses can be measured by the cold pressor test (CPT),that leads to increase in blood pressure and heart rate , or mental stress that is also known to stimulate cardiovascular responses. Individuals vary in their local and systemic vascular responses but the genetic determinants of these are not clear.
- Conditions
- Vascular Reaction to Medications
- Being tested
- Phenylephrine
- Keywords
- Hand vein sensitivity, phenylephrine, nitroglycerin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PhenylephrineDrug
Also called generic medications used,not applicable
Intravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min)
| Study group | Role | What they receive |
|---|---|---|
| African Americans | Experimental | Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing Receives: Drug: Phenylephrine |
| Caucasians | Experimental | Subjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing Receives: Drug: Phenylephrine |
What is being measured
The primary outcome is the main question the study is designed to answer.
ED50 After Phenylephrine
ED50 is a measurement of vein constriction and indicates 50% of maximal constriction after being given medication phenylephrine, representing sensitivity to the drug. Phenylephrine was infused at increasing dose rates, ranging from 12-9600 ng/min. The infusion at each dose rate lasted 7 minutes, with the vein diameter measured during the last 2 minutes of the infusion. The number represents the ng/ml of phenylephrine needed to reach 50% of maximal vein constriction. ED50 values were not normally distributed and were log-transformed for analysis and expressed as geometric means.
Measured: 70 minutes
Secondary outcomes (1)
Change in Blood Pressure
change in systolic and diastolic blood pressure, comparing before and after cold pressor test. A subset of 57 participants (of the 106) who were in the primary outcome measure also participated in the cold pressor test.
Measured: baseline to 2 minutes
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Feb 2009 (estimated)
- Study startJan 2009
- Primary completionDec 2010
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Vascular Reaction to MedicationsStudies 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 N/A
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 106 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
- Responsible party
- Principal investigator, C. Michael Stein, Vanderbilt University
- Investigators
- Charles M Stein, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00838695
- Sponsor's protocol ID
- 71148
- Other IDs
- P01HL056693, 1UL1RR024975
- Status last verified
- Oct 2018
- First submitted
- 4 Feb 2009
- Last updated
- 26 Oct 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Paranjape SY, Stein CM, Kurnik D. Blacks have a greater sensitivity to alpha1-adrenoceptor-mediated venoconstriction compared with whites. Hypertension. 2013 Apr;61(4):915-20. doi: 10.1161/HYPERTENSIONAHA.111.00854. Epub 2013 Feb 11.
PubMed 23399717Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J. 2015 Aug;15(4):310-5. doi: 10.1038/tpj.2014.69. Epub 2014 Nov 25.
PubMed 25421140Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Levinson RT, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1B-adrenergic receptor and vascular response. Pharmacogenomics J. 2017 Jul;17(4):366-371. doi: 10.1038/tpj.2016.29. Epub 2016 Apr 19.
PubMed 27089938
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Variability in Adrenergic Response
- ClinicalTrials.gov ID
- NCT00838695
- Acronym / sponsor ID
- 71148
- Conditions
- Vascular Reaction to Medications
- Keywords
- Hand vein sensitivity, phenylephrine, nitroglycerin
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 106 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI), National Center for Research Resources (NCRR)
- Study start
- Jan 2009
- Primary completion
- Dec 2010 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 6 Feb 2009 (estimated)
- Results
- Posted 26 Oct 2018
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 project is to determine the genetic factors contributing to interindividual differences in response to physiological and pharmacological vasoconstrictors and vasodilators.
Detailed description
The dorsal hand vein model is a relatively non-invasive and robust experimental model to examine the local in vivo effect of vasoactive drugs without elucidating systemic counterregulatory reflexes. Infusion of incremental low doses of phenylephrine into a dorsal hand vein results in increasing local venoconstriction, without systemic effects. Similarly, infusion of incremental low doses of nitroglycerin into a preconstricted dorsal hand vein results in increasing local venodilation, without systemic effects. Systemic vascular responses can be measured by the cold pressor test (CPT),that leads to increase in blood pressure and heart rate , or mental stress that is also known to stimulate cardiovascular responses. Individuals vary in their local and systemic vascular responses but the genetic determinants of these are not clear.
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| African Americans | Experimental | Drug: PhenylephrineSubjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing |
| Caucasians | Experimental | Drug: PhenylephrineSubjects' hand veins will be measured for maximum constriction while being infused with phenylephrine, and then mental stress and cold pressor testing |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Age between 18 and 40 years, inclusive.
- Subject must be willing to give written informed consent and be able to adhere to diet and study schedules.
- Subjects must be free of any clinically significant disease that requires a physician's care and/or would interfere with the study evaluations.
- Subjects must have a normal or clinically acceptable physical examination and ECG.
- Clinical laboratory tests (CBC, blood chemistries, and urinalysis) must be within normal limits or clinically acceptable to the investigator.
Key exclusion criteria (6 listed)
- Any subject who has taken any prescription or over-the-counter drugs, other than oral contraception if female, within two weeks prior to study drug administration.
- Subjects who are presently, or were formerly, narcotic addicts or alcoholics.
- Subjects who have a clinically significant allergy/intolerance to phenylephrine.
- Females with a positive serum/urine pregnancy test at screening.
- Females who are nursing.
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 |
|---|---|---|
| PhenylephrineAlso: generic medications used,not applicableIntravenous phenylephrine at low doses (approximately 10 doses ranging from 0-5000 ng/min) Intravenous nitroglycerin at low doses (approximately 10 doses ranging from 0.05-100 ng/min) | Drug | African Americans, Caucasians |
Primary outcome
ED50 After Phenylephrine
Time frame: 70 minutes
ED50 is a measurement of vein constriction and indicates 50% of maximal constriction after being given medication phenylephrine, representing sensitivity to the drug. Phenylephrine was infused at increasing dose rates, ranging from 12-9600 ng/min. The infusion at each dose rate lasted 7 minutes, with the vein diameter measured during the last 2 minutes of the infusion. The number represents the ng/ml of phenylephrine needed to reach 50% of maximal vein constriction. ED50 values were not normally distributed and were log-transformed for analysis and expressed as geometric means.
1 secondary outcome
Change in Blood Pressure
Time frame: baseline to 2 minutes
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23399717Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Paranjape SY, Stein CM, Kurnik D. Blacks have a greater sensitivity to alpha1-adrenoceptor-mediated venoconstriction compared with whites. Hypertension. 2013 Apr;61(4):915-20. doi: 10.1161/HYPERTENSIONAHA.111.00854. Epub 2013 Feb 11.
- Results publication: PubMed 25421140Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1A-adrenergic receptor and phenylephrine-mediated venoconstriction. Pharmacogenomics J. 2015 Aug;15(4):310-5. doi: 10.1038/tpj.2014.69. Epub 2014 Nov 25.
- Results publication: PubMed 27089938Adefurin A, Ghimire LV, Kohli U, Muszkat M, Sofowora GG, Li C, Levinson RT, Paranjape SY, Stein CM, Kurnik D. Genetic variation in the alpha1B-adrenergic receptor and vascular response. Pharmacogenomics J. 2017 Jul;17(4):366-371. doi: 10.1038/tpj.2016.29. Epub 2016 Apr 19.
Related trials for Vascular Reaction to Medications
Not yet recruiting
Stress Reactivity and Mother-Infant Cardiovascular Disease Risk
Maternal Health, Infant Health
RecruitingObservational study
A Precision Medicine Approach to Identify Patients Undergoing Elective PCI at Risk of Peri-PCI Myocardial Infarction
Coronary Artery Disease
Not yet recruiting
Incidence of Pruritus Using Intrathecal Fentanyl Versus Epidural Fentanyl to Initiate Labour Analgesia.
Pruritis, Hypotension Drug-Induced
Not yet recruitingPhase 4
Modulation of Gut MicroFLORA With Rifaximin to Reduce High Platelet Reactivity in Post-ACS Patients on Ticagrelor
ACS - Acute Coronary Syndrome, Ticagrelor
Recruiting
Tailored Anti-platelet Therapy After DES Implantation in High-risk Patients
Coronary Artery Disease
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.
Charles M Stein, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Phenylephrine in people with Vascular Reaction to Medications, run by Vanderbilt 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 5 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: finished, as of the sponsor's last update on 26 Oct 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Oct 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
ED50 After Phenylephrine (time frame: 70 minutes). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00838695, which also lists 3 linked publications.
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 Oct 2018.