Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
2002P-000067
Study information
Scientific title
Acronym
Study hypothesis
The primary hypothesis is that left ventricular function is impaired in diabetes, even in the absence of coronary artery disease. Protein kinase C (PKC) activation and endothelial dysfunction are the main factors that have been implicated in this. Valsartan may improve left ventricular function in the early stages and therefore, can be of help in patients without clinical cardiac abnormalities.
Ethics approval
Yes, first approved 23/01/2003
Study design
This is a randomized, double-blind, placebo-controlled, crossover trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Diabetes mellitus type 2
Intervention
Participants will be followed up for approximately 14 months. Each participant will be randomized to either placebo or Valsartan 160 mg/day for the first six months and then given the opposite treatment for the next six months. An eight-week wash out period (up to 4-6 months) will separate the two treatment periods. MRI of the heart and aorta will be performed at baseline and the end of each period of the study.
Intervention type
Drug
Phase
Not Specified
Drug names
Valsartan
Primary outcome measure
Changes in aortic elasticity (arterial compliance, stiffness index and pulse wave velocity) measured by MRI
Secondary outcome measures
Changes in ventricular function (the volumetric assessment of mass, end-diastolic and end-systolic volumes, ejection fraction (EF), stroke volume and cardiac output of the left and the right ventricles)
Overall trial start date
26/02/2003
Overall trial end date
30/06/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
We plan to study two groups with 15 subjects each:
1. Healthy non-diabetic subjects
2. Patients with type 2 diabetes with no severe long-term diabetes complications
For inclusion in the trial, patients must fulfil all of the following criteria:
1. All subjects will be ages 21-80 years
2. Healthy subjects - subjects should not be considered at higher risk than the general population to develop type 2 diabetes according to one of the following criteria:
a. Fasting plasma glucose <100 mg/dl and/or a 2-hour plasma glucose <140 during 75 gm oral glucose tolerance test (OGTT)
3. Patients with type 2 diabetes with no serious long-term complications
4. Individuals with a diagnosis of type 2 diabetes according to the American Diabetes Association criteria below, established in 1998. Subjects previously diagnosed with type 2 diabetes will not require a repeated diagnostic testing.
a. Unequivocal elevated plasma glucose level >200 mg/dl with symptoms suggestive of hyperglycemia (polyuria, polydipsia, weight loss)
b. Fasting plasma glucose levels >126 mg/dl
c. Two-hour plasma glucose >200 mg/dl during a 75 gm OGTT
In the absence of unequivocal hyperglycemia with acute metabolic decompensation, these criteria should be confirmed by repeat testing on a different day.
5. Prior to participation in this study, each subject must sign an informed consent form
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
30
Participant exclusion criteria
Active or uncontrolled cardiovascular disease as follows:
a. Coronary artery disease (CAD) (known CAD with previous diagnosis of definite acute myocardial infarction, unstable angina or stable angina)
b. Arrhythmia (uncontrolled, highly symptomatic, requires treatment or life-threatening)
c. Congestive heart failure (CHF) (New York Heart Association function class III and IV - symptoms of heart failure on less than ordinary exertion or at rest)
d. Stroke or transient ischemic attack with residual neurological damage
e. Uncontrolled hypertension: systolic blood pressure (SBP) >180 mmHg or diastolic blood pressure (DBP) >105 mmHg (two abnormal readings during visit)
f. Hypotension
2. Liver disease (alanine aminotranferease (ALT), aspartate aminotransferase (AST), alkaline phosphate levels >2 times upper normal limit) at the time of enrolment
3. Renal disease (macro-albuminuria) (2 of 3 urine specimens collected within a 3-6 month period with urine albumin ≥300 ug/mg creatinine - according to the American Diabetes Association (ADA) position statement)
4. Severe dyslipidemia (triglycerides >600 mg/dl or cholesterol >350 mg/dl). Subjects with hypertriglyceridemia may be re-tested in 2-3 weeks as the values can fluctuate tremendously within a few days. In the event that the re-tested value allows the patient to be enrolled, a planned deviation will be submitted to the Cardiovascular Credentialing International (CCI).
5. Any other serious chronic disease requiring active treatment
6. Females of childbearing potential not using an effective form of birth control as determined by the investigators
7. Subjects on any of the following medications:
a. Angiotensin II receptor antagonist treatment during last 3 months
b. Systemic glucocorticoids
c. Antineoplastic agents
d. Bronchodilators (aminophyline, inhaled beta agonists) on a regular basis
8. Claustrophobia
9. Subjects unable to have magnetic resonance imaging (MRI) scan according to the MRI clinical standards such as a pacemaker, defibrillator, eye implants and other metal implants or devices
Recruitment start date
26/02/2003
Recruitment end date
30/06/2007
Locations
Countries of recruitment
United States of America
Trial participating centre
330 Brookline Avenue
Boston
02215
United States of America
Funders
Funder type
Industry
Funder name
Novartis Pharmaceuticals
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list