Diabetes MellitusNCT00214825
Aldosterone and Vascular Disease in Diabetes Mellitus
A study testing eplerenone and Hydrochlorothiazide in people with Diabetes Mellitus and Endothelial Dysfunction, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
Specific aims for this proposal are to determine in patients with diabetes mellitus the effects of an aldosterone receptor antagonist on: 1. Coronary microvascular function assessed by MRI perfusion reserve, 2. Endothelial dysfunction assessed by brachial artery reactivity studies, and 3. Read more about this study
- Who is it for?
- Ages 21 to 64 years
- Conditions the study is for
- Diabetes Mellitus, Endothelial Dysfunction, Albuminuria
- What is being tested?
- eplerenone and Hydrochlorothiazide
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2003to Mar 2006
- Phase
- Interventional
- 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 21 to 64 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (over 30 mg/g creatinine).
Who cannot join
- Exclusion criteria include: (1) subjects without hypertension who have baseline systolic blood pressure <100 mmHg, (2) severe hypertension (blood pressure must be well-controlled on 3 antihypertensive agents or <150/100 mmHg on £2 antihypertensive agents), (3) ischemic changes on resting electrocardiogram, (4) clinical evidence of heart disease, cerebrovascular or peripheral vascular disease, (5) significant cardiac arrhythmias, (6) aortic stenosis, (7) 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia, (8) bronchospastic lung disease with active wheezing, (9) known hypersensitivity to any of the study drugs, (10) any contraindication to MRI, (11) serum creatinine ³ 1.5 mg/dL, (12) serum potassium ³ 5.0 mmol/L, (13) current smoker, (14) Serum transaminases greater than twice the upper limit of normal, (15) a history of gout, (16) pregnancy, and (17) other active medical problems detected by examination or laboratory testing.
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Specific aims for this proposal are to determine in patients with diabetes mellitus the effects of an aldosterone receptor antagonist on:
- Coronary microvascular function assessed by MRI perfusion reserve,
- Endothelial dysfunction assessed by brachial artery reactivity studies, and
- Inflammation assessed by blood measurements of c-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1).
Read the detailed description
Recent human and animal studies suggest that activation of the mineralocorticoid receptor (MR) by aldosterone, the final product of the renin-angiotensin-aldosterone system, causes microvascular damage, vascular inflammation, and endothelial dysfunction. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are unable to provide long-term aldosterone suppression. Therefore, we hypothesize that activation of the MR contributes to progression of vascular disease in patients with diabetes already using ACE inhibitor therapy.
Specific aims for this proposal are to determine in patients with type 1 or type 2 diabetes mellitus and proteinuria, already receiving ACE inhibitor or ARB therapy, the effects of an aldosterone receptor antagonist vs. hydrochlorothiazide on:
- Coronary microvascular function assessed by MRI perfusion reserve,
- Endothelial dysfunction assessed by brachial artery reactivity studies,
- Inflammation and cellular oxidative stress and injury, assessed by c-reactive protein (CRP), MCP-1, plasminogen activator inhibitor-1 (PAI-1).
- Proteinuria and whether there is a differential effect when a MR antagonist or HCTZ is added to the ACE inhibitor therapy.
This is a double-blind, randomized, cross-over study of men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (³30 mg/g creatinine). Participants will be randomized to a MR antagonist + placebo or HCTZ + potassium supplementation for 6 weeks. The MR antagonist arm will receive eplerenone 50 mg daily. The HCTZ arm will receive HCTZ 12.5 mg with potassium 10 Meq daily. Amlodipine 5 to 10 mg daily will be added during run phase to control blood pressure. Blood pressure goal is less than 130/80 mm Hg. There will be a 4-week washout period before the patients are crossed-over to the other study arm. MRI perfusion reserve, brachial artery reactivity, and blood samples will be obtained at the beginning and end of each treatment arm.
- Conditions
- Diabetes Mellitus, Endothelial Dysfunction, Albuminuria
- Being tested
- eplerenone, Hydrochlorothiazide
- Medical subject headings
- Diabetes Mellitus, Albuminuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
eplerenoneDrug
50 mg daily for 6 weeks with placebo
HydrochlorothiazideDrug
HCTZ 12.5 mg with potassium (10 mEq) daily for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | MR antagonist (Eplerenone) + placebo Receives: Drug: eplerenone |
| 2 | Placebo comparator | Hydrochlorothiazide plus potassium Receives: Drug: Hydrochlorothiazide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Coronary microvascular function assessed by myocardial perfusion reserve measured by MRI
Measured: 20 weeks
Secondary outcomes (3)
Endothelial dysfunction assessed by brachial artery reactivity
Measured: 20 weeks
Inflammation and cellular oxidative stress and injury, assessed by CRP, MCP-1, PAI-1, nephrin, cystanin C, F2 isoprostanes, and urinary 12-HETE
Measured: 20 weeks
Proteinuria
Measured: 20 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Sep 2005 (estimated)
- Study startAug 2003
- Primary completionMar 2006
- Study completionMar 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes MellitusStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Enrolment
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Investigators
- Gail K Adler, MD, PhD, Principal investigator, Brigham and Women's Hospital Boston, MA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00214825
- Sponsor's protocol ID
- 2003-P-001273 BWH
- Status last verified
- Dec 2007
- First submitted
- 20 Sep 2005
- Last updated
- 3 Jan 2008
- Results posted
- No
Publications
Joffe HV, Kwong RY, Gerhard-Herman MD, Rice C, Feldman K, Adler GK. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J Clin Endocrinol Metab. 2007 Jul;92(7):2552-8. doi: 10.1210/jc.2007-0393. Epub 2007 May 8.
PubMed 17488800
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aldosterone and Vascular Disease in Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00214825
- Acronym / sponsor ID
- 2003-P-001273 BWH
- Conditions
- Diabetes Mellitus, Endothelial Dysfunction, Albuminuria
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Institutes of Health (NIH)
- Study start
- Aug 2003
- Primary completion
- Mar 2006 (actual)
- Study completion
- Mar 2006 (actual)
- First posted
- 22 Sep 2005 (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.
Specific aims for this proposal are to determine in patients with diabetes mellitus the effects of an aldosterone receptor antagonist on:
- Coronary microvascular function assessed by MRI perfusion reserve,
- Endothelial dysfunction assessed by brachial artery reactivity studies, and
- Inflammation assessed by blood measurements of c-reactive protein (CRP), monocyte chemoattractant protein-1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1).
Detailed description
Recent human and animal studies suggest that activation of the mineralocorticoid receptor (MR) by aldosterone, the final product of the renin-angiotensin-aldosterone system, causes microvascular damage, vascular inflammation, and endothelial dysfunction. Angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are unable to provide long-term aldosterone suppression. Therefore, we hypothesize that activation of the MR contributes to progression of vascular disease in patients with diabetes already using ACE inhibitor therapy.
Specific aims for this proposal are to determine in patients with type 1 or type 2 diabetes mellitus and proteinuria, already receiving ACE inhibitor or ARB therapy, the effects of an aldosterone receptor antagonist vs. hydrochlorothiazide on:
- Coronary microvascular function assessed by MRI perfusion reserve,
- Endothelial dysfunction assessed by brachial artery reactivity studies,
- Inflammation and cellular oxidative stress and injury, assessed by c-reactive protein (CRP), MCP-1, plasminogen activator inhibitor-1 (PAI-1).
- Proteinuria and whether there is a differential effect when a MR antagonist or HCTZ is added to the ACE inhibitor therapy.
This is a double-blind, randomized, cross-over study of men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (³30 mg/g creatinine). Participants will be randomized to a MR antagonist + placebo or HCTZ + potassium supplementation for 6 weeks. The MR antagonist arm will receive eplerenone 50 mg daily. The HCTZ arm will receive HCTZ 12.5 mg with potassium 10 Meq daily. Amlodipine 5 to 10 mg daily will be added during run phase to control blood pressure. Blood pressure goal is less than 130/80 mm Hg. There will be a 4-week washout period before the patients are crossed-over to the other study arm. MRI perfusion reserve, brachial artery reactivity, and blood samples will be obtained at the beginning and end of each treatment arm.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: eplerenoneMR antagonist (Eplerenone) + placebo |
| 2 | Placebo comparator | Drug: HydrochlorothiazideHydrochlorothiazide plus potassium |
Who may qualify
- Ages
- 21 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (1 listed)
- Men and women (21-64 years old) with type 1 or type 2 diabetes mellitus and albuminuria (over 30 mg/g creatinine).
Key exclusion criteria (1 listed)
- Exclusion criteria include: (1) subjects without hypertension who have baseline systolic blood pressure <100 mmHg, (2) severe hypertension (blood pressure must be well-controlled on 3 antihypertensive agents or <150/100 mmHg on £2 antihypertensive agents), (3) ischemic changes on resting electrocardiogram, (4) clinical evidence of heart disease, cerebrovascular or peripheral vascular disease, (5) significant cardiac arrhythmias, (6) aortic stenosis, (7) 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia, (8) bronchospastic lung disease with active wheezing, (9) known hypersensitivity to any of the study drugs, (10) any contraindication to MRI, (11) serum creatinine ³ 1.5 mg/dL, (12) serum potassium ³ 5.0 mmol/L, (13) current smoker, (14) Serum transaminases greater than twice the upper limit of normal, (15) a history of gout, (16) pregnancy, and (17) other active medical problems detected by examination or laboratory testing.
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 |
|---|---|---|
| eplerenone50 mg daily for 6 weeks with placebo | Drug | 1 |
| HydrochlorothiazideHCTZ 12.5 mg with potassium (10 mEq) daily for 6 weeks | Drug | 2 |
Primary outcome
Coronary microvascular function assessed by myocardial perfusion reserve measured by MRI
Time frame: 20 weeks
3 secondary outcomes
Endothelial dysfunction assessed by brachial artery reactivity
Time frame: 20 weeks
Inflammation and cellular oxidative stress and injury, assessed by CRP, MCP-1, PAI-1, nephrin, cystanin C, F2 isoprostanes, and urinary 12-HETE
Time frame: 20 weeks
Proteinuria
Time frame: 20 weeks
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 3 Jan 2008.
- Results publication: PubMed 17488800Joffe HV, Kwong RY, Gerhard-Herman MD, Rice C, Feldman K, Adler GK. Beneficial effects of eplerenone versus hydrochlorothiazide on coronary circulatory function in patients with diabetes mellitus. J Clin Endocrinol Metab. 2007 Jul;92(7):2552-8. doi: 10.1210/jc.2007-0393. Epub 2007 May 8.
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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.
Gail K Adler, MD, PhD principal investigator
Brigham and Women's Hospital Boston, MA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing eplerenone and Hydrochlorothiazide in people with Diabetes Mellitus and Endothelial Dysfunction, run by Brigham and Women's Hospital 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 1 inclusion and 1 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 3 Jan 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. Some participants in this study may receive a placebo. 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.
What does the primary outcome measure?
Coronary microvascular function assessed by myocardial perfusion reserve measured by MRI (time frame: 20 weeks). 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 NCT00214825, 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 3 Jan 2008.