HypercholesterolemiaNCT00006071
Effects of Rosiglitazone on Blood Vessels in Patients With High Blood Pressure and High Cholesterol
An observational study of Hypercholesterolemia and Hypertension, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
Trial summary
Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Hypercholesterolemia, Hypertension
- How many people
- 120 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2000to Mar 2001
- Phase
- Observational
- 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 Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Patients must discontinue all hypertensive therapy two weeks prior to entering this study.
Patient with a serum cholesterol value of 240 mg/dl or greater.
Patients must discontinue all lipid-lowering agents 1 month prior to entering this study.
No patients with evidence of active liver disease (e.g. ALT greater than 1.5 times the upper limit of normal).
No history of diabetes, peripheral vascular disease, coagulopathy, or any other disease predisposing to vasculitis or Raynaud's phenomenon.
No women with childbearing potential unless they use an effective contraceptive method.
Trial locations and contacts
1 site in 1 country.
United States1 site
National Heart, Lung and Blood Institute (NHLBI)
Bethesda, Maryland, 20892
About this study
Official title: Effects of Rosiglitazone on Endothelium-Dependent Vasodilation and on Endothelin Activity in Patients With Essential Hypertension and in Patients With Hypercholesterolemia
Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. This study will investigate the effects of rosiglitazone-a drug used to improve the action of insulin in diabetic patients-on blood flow by examining its effects on endothelin (a substance that causes vessel constriction), and other substances produced by the vessel-lining cells.
Adults with blood pressure recordings of 140/90 mmHg or higher on at least three separate days or with a blood cholesterol level of at least 240 mg/dl may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood pressure recordings, blood and urine tests.
Read more
This "crossover" study involves two separate treatment periods; that is, participants will take either rosiglitazone or placebo (an inactive look-alike pill) once a day for 8 weeks, then no drug for 4 weeks, and then the alternative treatment for the next 8 weeks. Patients will continue to take their high blood pressure medicines during the first 6 weeks of each treatment period. They will stop the medication 2 weeks before the following procedures, which are done at the end of each 8-week treatment period:
Strain gauge plethysmography-A small catheter is placed through a needle into an artery at the bend of the arm for measuring blood pressure and drawing blood samples during the study. Pressure cuffs are placed on the wrist and upper arm, and a strain gauge (a rubber band device) is placed around the forearm to measure forearm blood flow. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow, and the measurement is recorded.
Small doses of four drugs-acetylcholine, bradykinin, sodium nitroprusside and BQ-123-are given through the catheter. Acetylcholine slows the heart rate. Bradykinin stimulates the release of a substance that causes blood vessels to dilate and can lower blood pressure. Sodium nitroprusside causes blood vessels to dilate and is used to treat high blood pressure and heart failure. BQ-123 blocks the blood vessel-constricting activity of endothelin.
Brachial ultrasound reactivity study-A baseline ultrasound image (picture produced using sound waves) of the brachial artery (artery located at the bend of the arm) is taken and blood flow measurements are recorded. Then, a pressure cuff is placed around the upper forearm, inflated for 5 minutes to stop blood flow to the forearm, and then released. Images of the artery and flow measurements are repeated. After a 15-minute rest, new baseline images are taken and flow measurements obtained. A small amount of nitroglycerin is then sprayed under the tongue and after 3 minutes, blood flow measurements and brachial artery images are recorded once more.
Read the detailed description
Since the publication of the data of the San Antonio Heart Study, the link between metabolic and cardiovascular disorders has been increasingly recognized, as well as the features these disorders have in common: insulin resistance and vascular endothelial dysfunction. Therefore, we are interested in the mechanisms underlying the impairment of endothelial function in insulin-resistant states. In particular, we have recently found that insulin stimulates the vascular activity of both ET-1 and NO in the normal human vasculature. It is therefore reasonable to speculate that the occurrence of insulin resistance and/or endothelial dysfunction may lead to an imbalance in this mechanism with a resulting increased vascular activity of ET-1.
A new class of insulin sensitizing agents, the thiazolidinediones, have been shown to possess, in addition to their numerous metabolic roles, positive effects on blood pressure and on vascular endothelial function, including decreased endothelin-1 production and reduced circulating levels of endothelial surface molecules. Based on these data, we plan to investigate the hypothesis that thiazolidinediones may improve both insulin resistance and endothelial dysfunction in essential hypertension and hypercholesterolemia. We hypothesize that treatment with rosiglitazone improves endothelium-dependent vascular relaxation in both conductance and resistance vessels, decreases vascular endothelin-1 activity and reduces plasma levels of leptin and of markers of endothelial activation.
- Conditions
- Hypercholesterolemia, Hypertension
- Keywords
- Brachial Reactivity, Endothelial Function, Endothelial Markers, Forearm Flow, Insulin Resistance, Elevated Cholesterol, Hypertension
- Medical subject headings
- Hypercholesterolemia, Hypertension, Insulin Resistance
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2002 (estimated)
- Study startJul 2000
- Study completionMar 2001
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for HypercholesterolemiaStudies of the same condition, open and under way.
- More trials run by National Heart, Lung, and Blood Institute (NHLBI)The sponsor's other registered studies.
- 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
- Observational
- Enrolment
- 120 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00006071
- Sponsor's protocol ID
- 000175
- Other IDs
- 00-H-0175
- Status last verified
- Jul 2000
- First submitted
- 21 Jul 2000
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Kiowski W, Luscher TF, Linder L, Buhler FR. Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation. 1991 Feb;83(2):469-75. doi: 10.1161/01.cir.83.2.469.
PubMed 1846783Gryglewski RJ, Botting RM, Vane JR. Mediators produced by the endothelial cell. Hypertension. 1988 Dec;12(6):530-48. doi: 10.1161/01.hyp.12.6.530.
PubMed 3060428Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27-36. doi: 10.1056/NEJM199007053230106. No abstract available.
PubMed 2113184
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effects of Rosiglitazone on Endothelium-Dependent Vasodilation and on Endothelin Activity in Patients With Essential Hypertension and in Patients With Hypercholesterolemia
- ClinicalTrials.gov ID
- NCT00006071
- Acronym / sponsor ID
- 000175
- Conditions
- Hypercholesterolemia, Hypertension
- Keywords
- Brachial Reactivity, Endothelial Function, Endothelial Markers, Forearm Flow, Insulin Resistance, Elevated Cholesterol, Hypertension
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 120 participants
- Lead sponsor
- National Heart, Lung, and Blood Institute (NHLBI)US National Institutes of Health
- Study start
- Jul 2000
- Study completion
- Mar 2001
- First posted
- 10 Dec 2002 (estimated)
- 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.
Cells in the lining of blood vessels produce various substances that cause the vessels to dilate (relax) and constrict (tighten), thereby regulating blood flow. In patients with high blood pressure and high cholesterol, the blood vessels do not dilate properly. This study will investigate the effects of rosiglitazone-a drug used to improve the action of insulin in diabetic patients-on blood flow by examining its effects on endothelin (a substance that causes vessel constriction), and other substances produced by the vessel-lining cells.
Adults with blood pressure recordings of 140/90 mmHg or higher on at least three separate days or with a blood cholesterol level of at least 240 mg/dl may be eligible for this study. Candidates will be screened with a medical history and physical examination, blood pressure recordings, blood and urine tests.
This "crossover" study involves two separate treatment periods; that is, participants will take either rosiglitazone or placebo (an inactive look-alike pill) once a day for 8 weeks, then no drug for 4 weeks, and then the alternative treatment for the next 8 weeks. Patients will continue to take their high blood pressure medicines during the first 6 weeks of each treatment period. They will stop the medication 2 weeks before the following procedures, which are done at the end of each 8-week treatment period:
Strain gauge plethysmography-A small catheter is placed through a needle into an artery at the bend of the arm for measuring blood pressure and drawing blood samples during the study. Pressure cuffs are placed on the wrist and upper arm, and a strain gauge (a rubber band device) is placed around the forearm to measure forearm blood flow. When the cuffs are inflated, blood flows into the arm, stretching the strain gauge at a rate proportional to the flow, and the measurement is recorded.
Small doses of four drugs-acetylcholine, bradykinin, sodium nitroprusside and BQ-123-are given through the catheter. Acetylcholine slows the heart rate. Bradykinin stimulates the release of a substance that causes blood vessels to dilate and can lower blood pressure. Sodium nitroprusside causes blood vessels to dilate and is used to treat high blood pressure and heart failure. BQ-123 blocks the blood vessel-constricting activity of endothelin.
Brachial ultrasound reactivity study-A baseline ultrasound image (picture produced using sound waves) of the brachial artery (artery located at the bend of the arm) is taken and blood flow measurements are recorded. Then, a pressure cuff is placed around the upper forearm, inflated for 5 minutes to stop blood flow to the forearm, and then released. Images of the artery and flow measurements are repeated. After a 15-minute rest, new baseline images are taken and flow measurements obtained. A small amount of nitroglycerin is then sprayed under the tongue and after 3 minutes, blood flow measurements and brachial artery images are recorded once more.
Detailed description
Since the publication of the data of the San Antonio Heart Study, the link between metabolic and cardiovascular disorders has been increasingly recognized, as well as the features these disorders have in common: insulin resistance and vascular endothelial dysfunction. Therefore, we are interested in the mechanisms underlying the impairment of endothelial function in insulin-resistant states. In particular, we have recently found that insulin stimulates the vascular activity of both ET-1 and NO in the normal human vasculature. It is therefore reasonable to speculate that the occurrence of insulin resistance and/or endothelial dysfunction may lead to an imbalance in this mechanism with a resulting increased vascular activity of ET-1.
A new class of insulin sensitizing agents, the thiazolidinediones, have been shown to possess, in addition to their numerous metabolic roles, positive effects on blood pressure and on vascular endothelial function, including decreased endothelin-1 production and reduced circulating levels of endothelial surface molecules. Based on these data, we plan to investigate the hypothesis that thiazolidinediones may improve both insulin resistance and endothelial dysfunction in essential hypertension and hypercholesterolemia. We hypothesize that treatment with rosiglitazone improves endothelium-dependent vascular relaxation in both conductance and resistance vessels, decreases vascular endothelin-1 activity and reduces plasma levels of leptin and of markers of endothelial activation.
Study design
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Not reported in the source record.
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 4 Mar 2008.
- Background: PubMed 1846783Kiowski W, Luscher TF, Linder L, Buhler FR. Endothelin-1-induced vasoconstriction in humans. Reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation. 1991 Feb;83(2):469-75. doi: 10.1161/01.cir.83.2.469.
- Background: PubMed 3060428Gryglewski RJ, Botting RM, Vane JR. Mediators produced by the endothelial cell. Hypertension. 1988 Dec;12(6):530-48. doi: 10.1161/01.hyp.12.6.530.
- Background: PubMed 2113184Vane JR, Anggard EE, Botting RM. Regulatory functions of the vascular endothelium. N Engl J Med. 1990 Jul 5;323(1):27-36. doi: 10.1056/NEJM199007053230106. No abstract available.
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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?
An observational study of Hypercholesterolemia and Hypertension, run by National Heart, Lung, and Blood Institute (NHLBI) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Mar 2008. 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?
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00006071, 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 4 Mar 2008.