ObesityNCT00685945
Renin-Angiotensin Aldosterone System and Fibrinolysis Interaction in Humans-Specific Aim 3
A study testing L-NMMA + bradykinin, Isosorbide + L-NMMA + bradykinin and Sildenafil + L-NMMA + bradykinin in people with Obesity, run by Vanderbilt University at 1 site in United States.
Trial summary
The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- L-NMMA + bradykinin, Isosorbide + L-NMMA + bradykinin and Sildenafil + L-NMMA + bradykinin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteUnited States
- Study dates
- Dec 2007to Jan 2009
- 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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18-70 years of age
- Male and female subjects
- Surgical sterilization
- Childbearing potential: beta HCG on study day
- Subjects with a body mass index of 25 or greater
Who cannot join
- Diabetes type 1 to type 2 as defined by a fasting glucose of 126 mg/dl or greater or the use of anti-diabetic medication
- Use of hormone replacement therapy
- Statin therapy
- In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg or taking hypertensives
- Pregnancy/Breast Feeding
- Cardiovascular disease such as myocardial infarction with 6 months prior to enrollment, presence of angina pectoris, significant arrhythmia, congestive heart failure (LV hypertrophy acceptable) deep vein thrombosis, pulmonary embolism, second or three degree heart block, mitral valve stenosis, aortic stenosis, or hypertrophic cardiomyopathy
Show all 22Show fewer
- Treatment with anticoagulants
- History of serious neurologic disease such as cerebral hemorrhage, stroke or transient ischemic attack
- Diagnosis of asthma
- Clinically significant gastrointestinal impairment that could interfere with drug absorption
- Hematocrit <35%
- Hyperlipidemic fasting Total Cholesterol >220mg/dl
- Impaired renal function (Serum creatinine >1.5 mg/dl)
- History or presence of immunological or hematological disorders
- Any underlying or acute disease requiring regular medication which could possible pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
- Impaired hepatic function (Serum glutamic oxaloacetic transaminase, serum glutamate pyruvate transaminase > 60)
- Treatment with chronic systemic glucocorticoid therapy (more than 7 days in 1 month)
- Treatment with lithium salts
- History of Alcohol or drug abuse
- Treatment with any investigational drug 1 month preceding study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center-GCRC
Nashville, Tennessee, 37232
About this study
Official title: Renin-Angiotensin Aldosterone System and Fibrinolysis(RAAS) Interaction in Humans- Specific Aim 3
The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.
Read the detailed description
To test the hypothesis that the administration of the NO donor isosorbide dinitrate,but not the phosphodiesterase inhibitor sildenafil, will attenuate stimulated vascular t-PA release whereas both agents will improve glucose uptake.
- Conditions
- Obesity
- Being tested
- Control (bradykinin), L-NMMA + bradykinin, Isosorbide + L-NMMA + bradykinin, Sildenafil + L-NMMA + bradykinin
- Keywords
- Bradykinin, Obesity, Nitric Oxide Donor, tissue type plasminogen activator, isosorbide dinitrate, phosphodiesterase inhibitor, Renin-Angiotensin Aldosterone System, Fibrinolysis, Angiotensin converting enzyme
- Medical subject headings
- Obesity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Control (bradykinin)Drug
Graded doses of bradykinin (Clinalfa AG, Läufelfingen, Switzerland) will be infused at 50, 100, and 200ng/min. Each dose will be infused for 5 minutes and FBF will measured during the last 2 minutes of infusion. Arterial and venous blood samples will be obtained for measurement of net t-PA release after each dose.
L-NMMA + bradykininDrug
Also called N-monomethyl-L-arginine
Thirty minutes after administration of bradykinin a continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be started started. While continuing the infusion of L-NMMA, baseline measurements and infusion of bradykinin will be repeated.
Isosorbide + L-NMMA + bradykininDrug
Following the second bradykinin infusion, 12 subjects will receive 5mg isosorbide dinitrate (an exogenous NO donor; Major Pharmaceuticals Inc, Livonia MI). Sixty minutes after the administration of isosorbide the continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be restarted and baseline measurements and bradykinin infusion will be repeated.
Sildenafil + L-NMMA + bradykininDrug
Following the second bradykinin infusion, 12 subjects will receive 50mg sildenafil (phosphodiesterase type 5 (PDE5) inhibitor to increase cGMP without increasing NO; Pfizer, NY). Sixty minutes after the administration of sildenafil the continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be restarted and baseline measurements and bradykinin infusion will be repeated.
| Study group | Role | What they receive |
|---|---|---|
| Control (bradykinin infusion) | Experimental | Bradykinin (Clinalfa AG, Läufelfingen, Switzerland) Receives: Drug: Control (bradykinin) |
| L-NMMA + bradykinin | Experimental | N-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor; Bachem, Torrance, CA) Receives: Drug: L-NMMA + bradykinin |
| Isosorbide + L-NMMA + bradykinin | Experimental | Isosorbide (NO donor) Receives: Drug: Isosorbide + L-NMMA + bradykinin |
| Sildenafil + L-NMMA + bradykinin | Experimental | Sildenafil (phosphodiesterase type 5 (PDE5) inhibitor Receives: Drug: Sildenafil + L-NMMA + bradykinin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Net Tissue-type Plasminogen Activator (t-PA) Release
Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively.
Measured: During and after each study drug administration
Secondary outcomes (1)
Forearm Blood Flow (FBF)
Forearm blood flow was measured by strain gauge plethysmography
Measured: During and after each study drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 May 2008 (estimated)
- Study startDec 2007
- Primary completionJan 2009
- Study completionJan 2009
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 (1)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies 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
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Research Resources (NCRR), National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Nancy J. Brown, Vanderbilt University
- Investigators
- Nancy J Brown, MD, Principal investigator, Vanderbilt University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00685945
- Sponsor's protocol ID
- RAAS & Fibrinolysis
- Other IDs
- 2R01HL060906, HL065193, UL1RR024975, 5R01HL085740-05
- Status last verified
- Jan 2013
- First submitted
- 27 May 2008
- Last updated
- 25 Feb 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Pretorius M, Brown NJ. Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissue-type plasminogen activator release. J Pharmacol Exp Ther. 2010 Jan;332(1):291-7. doi: 10.1124/jpet.109.160168. Epub 2009 Oct 19.
PubMed 19841473
Study at a glance
From the registry record, last updated by the sponsor on 25 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Renin-Angiotensin Aldosterone System and Fibrinolysis(RAAS) Interaction in Humans- Specific Aim 3
- ClinicalTrials.gov ID
- NCT00685945
- Acronym / sponsor ID
- RAAS & Fibrinolysis
- Conditions
- Obesity
- Keywords
- Bradykinin, Obesity, Nitric Oxide Donor, tissue type plasminogen activator, isosorbide dinitrate, phosphodiesterase inhibitor, Renin-Angiotensin Aldosterone System, Fibrinolysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH), National Center for Research Resources (NCRR), National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Dec 2007
- Primary completion
- Jan 2009 (actual)
- Study completion
- Jan 2009 (actual)
- First posted
- 29 May 2008 (estimated)
- Results
- Posted 25 Feb 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study is to determine if giving isosorbide,a drug that is used to treat chest pain, affects blood vessel release of an anti-clotting factor.
Detailed description
To test the hypothesis that the administration of the NO donor isosorbide dinitrate,but not the phosphodiesterase inhibitor sildenafil, will attenuate stimulated vascular t-PA release whereas both agents will improve glucose uptake.
Study design
- Primary purpose
- Health services research
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Control (bradykinin infusion) | Experimental | Drug: Control (bradykinin)Bradykinin (Clinalfa AG, Läufelfingen, Switzerland) |
| L-NMMA + bradykinin | Experimental | Drug: L-NMMA + bradykininN-monomethyl-L-arginine (L-NMMA, NO synthase inhibitor; Bachem, Torrance, CA) |
| Isosorbide + L-NMMA + bradykinin | Experimental | Drug: Isosorbide + L-NMMA + bradykininIsosorbide (NO donor) |
| Sildenafil + L-NMMA + bradykinin | Experimental | Drug: Sildenafil + L-NMMA + bradykininSildenafil (phosphodiesterase type 5 (PDE5) inhibitor |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 18-70 years of age
- Male and female subjects
- Surgical sterilization
- Childbearing potential: beta HCG on study day
- Subjects with a body mass index of 25 or greater
Key exclusion criteria (22 listed)
- Diabetes type 1 to type 2 as defined by a fasting glucose of 126 mg/dl or greater or the use of anti-diabetic medication
- Use of hormone replacement therapy
- Statin therapy
- In hypertensive subjects, a seated systolic blood pressure greater than 179 mmHg or a seated diastolic blood pressure greater than 110 mmHg or taking hypertensives
- Pregnancy/Breast Feeding
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 (bradykinin)Graded doses of bradykinin (Clinalfa AG, Läufelfingen, Switzerland) will be infused at 50, 100, and 200ng/min. Each dose will be infused for 5 minutes and FBF will measured during the last 2 minutes of infusion. Arterial and venous blood samples will be obtained for measurement of net t-PA release after each dose. | Drug | Control (bradykinin infusion) |
| L-NMMA + bradykininAlso: N-monomethyl-L-arginineThirty minutes after administration of bradykinin a continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be started started. While continuing the infusion of L-NMMA, baseline measurements and infusion of bradykinin will be repeated. | Drug | L-NMMA + bradykinin |
| Isosorbide + L-NMMA + bradykininFollowing the second bradykinin infusion, 12 subjects will receive 5mg isosorbide dinitrate (an exogenous NO donor; Major Pharmaceuticals Inc, Livonia MI). Sixty minutes after the administration of isosorbide the continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be restarted and baseline measurements and bradykinin infusion will be repeated. | Drug | Isosorbide + L-NMMA + bradykinin |
| Sildenafil + L-NMMA + bradykininFollowing the second bradykinin infusion, 12 subjects will receive 50mg sildenafil (phosphodiesterase type 5 (PDE5) inhibitor to increase cGMP without increasing NO; Pfizer, NY). Sixty minutes after the administration of sildenafil the continuous intra-arterial infusion of L-NMMA at 12 micromol/min will be restarted and baseline measurements and bradykinin infusion will be repeated. | Drug | Sildenafil + L-NMMA + bradykinin |
Primary outcome
Net Tissue-type Plasminogen Activator (t-PA) Release
Time frame: During and after each study drug administration
Individual net t-PA release at each time point were calculated by the following formula: net release = (Cv-CA) x {FBF x [101-hematocrit/100]}, where Cv and CA represent the concentration of t-PA in the brachial vein and artery, respectively.
1 secondary outcome
Forearm Blood Flow (FBF)
Time frame: During and after each study drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Feb 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 19841473Pretorius M, Brown NJ. Endogenous nitric oxide contributes to bradykinin-stimulated glucose uptake but attenuates vascular tissue-type plasminogen activator release. J Pharmacol Exp Ther. 2010 Jan;332(1):291-7. doi: 10.1124/jpet.109.160168. Epub 2009 Oct 19.
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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.
Nancy J Brown, MD principal investigator
Vanderbilt University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing L-NMMA + bradykinin, Isosorbide + L-NMMA + bradykinin and Sildenafil + L-NMMA + bradykinin in people with Obesity, 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 22 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 25 Feb 2013. 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 25 Feb 2013). 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?
Net Tissue-type Plasminogen Activator (t-PA) Release (time frame: During and after each study drug administration). 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 NCT00685945, which also lists 1 linked publication.
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 25 Feb 2013.