- ICH GCP
- Registre américain des essais cliniques
- Essai clinique NCT00865124
Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease
Aldosterone is a significant mediator of cardiovascular injury associated with heart failure and the cardiovascular benefits of mineralocorticoid receptor blockade are additive to those of angiotensin converting enzyme inhibitors or angiotensin II (ANGII) receptor blockers. This study will test the hypothesis that mineralocorticoid receptor (MR) antagonists exert beneficial cardiovascular effects, specifically by decreasing vascular injury and improving vascular function. A randomized, double-blind study will be conducted, in which participants with Type 2 Diabetes Mellitus will undergo a series of assessments to test heart, blood vessel, and kidney function at baseline, and after 2 and 6 months of treatment with one of the following drugs:
- spironolactone
- hydrochlorothiazide (HCTZ) plus potassium
- placebo
In the event of insufficient funds, randomization to the placebo arm will be stopped and primary assessment of outcomes will occur at baseline and after 6 months of treatment.
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Type d'étude
Inscription (Réel)
Phase
- N'est pas applicable
Contacts et emplacements
Lieux d'étude
-
-
Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Brigham and Women's Hospital
-
-
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- age 18-70 years
- type 2 diabetes mellitus
- with or without hypertension
Exclusion Criteria:
- ischemic changes on resting electrocardiogram,
- clinical evidence of heart disease (angina, heart failure, unstable angina),cerebrovascular or peripheral vascular disease,
- significant cardiac arrhythmias,
- aortic stenosis,
- 2nd or 3rd degree atrio-ventricular block, sinus node disease, or symptomatic bradycardia,
- bronchospastic lung disease with active wheezing,
- known hypersensitivity to adenosine,
- hemoglobin A1C (HbA1c) > 8.5%, *
- gout (If not already taking HCTZ),
- the use of Rosiglitazone,**
- estimated glomerular filtration rate (eGFR) < 60 ml/min,
- serum potassium > 5.0 mmol/L,
- use of potassium-sparing diuretics,**
- current smoker,*
- pregnancy,
- renal disease not related to diabetes mellitus,
- uncontrolled hypertension, systolic blood pressure (BP) >160 mm Hg and diastolic BP >100 mm Hg,*
- use of cyclic hormone replacement therapy
- past intolerance of angiotensin-converting enzyme (ACE) inhibitor therapy
- other major medical illnesses. Participants with evidence of a previous myocardial infarction on the first adenosine-stimulated positron emission tomography (PET) study will be withdrawn from the study.
Screening systolic blood pressure < 105 mm Hg off of anti-hypertensive medications
Participants can enroll in study and proceed with in-patient evaluations if during the run-in period adjustments of medications, diet and habits lead to improved glucose control [equivalent to HbA1c <8.5%, controlled hypertension and cessation of smoking.
- Participants who are currently taking these medications will not qualify for a screening visit. If medications were recently stopped by the participant's physician, he or she may be screened but the baseline assessment protocol must occur 3 months after stopping.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Double
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Comparateur placebo: Gélule placebo
|
Placebo capsule daily
|
Expérimental: Spironolactone (mineralocorticoid receptor [MR] blockade)
|
25 mg capsule daily for 6 months
|
Comparateur actif: Hydrochlorothiazide + potassium
|
hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily
|
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change in Coronary Flow Reserve From Baseline to 6 Months
Délai: Baseline and six months
|
Coronary flow reserve (CFR), or myocardial perfusion reserve, was assessed via cardiac positron emission tomography (PET).
CFR is the ratio of adenosine-stimulated blood flow through myocardium to resting blood flow through myocardium.
An improvement in coronary flow reserve is beneficial.
|
Baseline and six months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function
Délai: Baseline and six months
|
Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment.
|
Baseline and six months
|
Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II)
Délai: Baseline and six months
|
Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment; and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.
|
Baseline and six months
|
Change in Renal Plasma Flow
Délai: Baseline and six months
|
Renal vasculature was assessed by examining renal plasma flow, or para-aminohippurate (PAH) clearance, basally and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.
|
Baseline and six months
|
Collaborateurs et enquêteurs
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Gail K Adler, MD, PhD, Brigham and Women's Hospital
Publications et liens utiles
Publications générales
- Haas AV, Rosner BA, Kwong RY, Rao AD, Garg R, Di Carli MF, Adler GK. Sex Differences in Coronary Microvascular Function in Individuals With Type 2 Diabetes. Diabetes. 2019 Mar;68(3):631-636. doi: 10.2337/db18-0650. Epub 2018 Nov 8.
- Garg R, Rao AD, Baimas-George M, Hurwitz S, Foster C, Shah RV, Jerosch-Herold M, Kwong RY, Di Carli MF, Adler GK. Mineralocorticoid receptor blockade improves coronary microvascular function in individuals with type 2 diabetes. Diabetes. 2015 Jan;64(1):236-42. doi: 10.2337/db14-0670. Epub 2014 Aug 14.
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Troubles du métabolisme du glucose
- Maladies métaboliques
- Maladies du système endocrinien
- Diabète sucré
- Maladies cardiovasculaires
- Diabète sucré, Type 2
- Maladies vasculaires
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents antihypertenseurs
- Hormones, substituts hormonaux et antagonistes hormonaux
- Agents natriurétiques
- Modulateurs de transport membranaire
- Diurétiques
- Antagonistes hormonaux
- Antagonistes des récepteurs minéralocorticoïdes
- Diurétiques, épargneurs de potassium
- Inhibiteurs des Symporteurs de Chlorure de Sodium
- Spironolactone
- Hydrochlorothiazide
Autres numéros d'identification d'étude
- 2007-P-000564
- 1R01HL087060-01A2 (Subvention/contrat des NIH des États-Unis)
Ces informations ont été extraites directement du site Web clinicaltrials.gov sans aucune modification. Si vous avez des demandes de modification, de suppression ou de mise à jour des détails de votre étude, veuillez contacter register@clinicaltrials.gov. Dès qu'un changement est mis en œuvre sur clinicaltrials.gov, il sera également mis à jour automatiquement sur notre site Web .
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