Condition category
Nutritional, Metabolic, Endocrine
Date applied
20/01/2006
Date assigned
17/05/2006
Last edited
17/05/2006
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr Aristidis Veves

ORCID ID

Contact details

330 Brookline Avenue
Palmer 321
Boston
02215
United States of America

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 measures

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

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

Sponsor information

Organisation

Beth Israel Deaconess Medical Centre (USA)

Sponsor details

330 Brookline Avenue
Palmer 321
Boston
02215
United States of America

Sponsor type

Hospital/treatment centre

Website

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

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes