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Metabolic SyndromePhase 4NCT00745953

Regression of Fatty Heart by Valsartan Therapy

A Phase 4 study testing Valsartan and Hydrochlorothiazide in people with Metabolic Syndrome and Lipotoxicity, run by University of Texas Southwestern Medical Center at 1 site in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial summary

Traditionally, obesity is considered an indirect cause of heart disease. Obese individuals typically present with a number of traditional Framingham risk factors (hypertension, dyslipidemia, and type 2 diabetes), predisposing them to heart attacks and subsequent heart failure. Read more about this study

Who is it for?
Ages 18 to 50 years
Conditions the study is for
Metabolic Syndrome, Lipotoxicity
What is being tested?
Valsartan and Hydrochlorothiazide
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteUnited States
Study dates
Aug 2007to Aug 2009
Phase
Phase 4
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 18 to 50 years
  • All sexes
  • No healthy volunteers
  • Adult

Who may be able to join

  • Prediabetic individuals with impaired glucose tolerance (2 hr postprandial glucose > 140mg/dL) or having 3 of 5 Metabolic Syndrome criteria:
  • Fasting glucose > 100mg/dL;
  • Waist circumference: men > 102cm, women > 88cm (confirmed with abdominal MRI);
  • HDL: men < 40mg/dL, women < 50mg/dL;
  • Triglycerides > 150mg/dL;
  • Blood pressure > 130/80mmHg;
Show all 9Show fewer
  • Elevated hepatic triglycerides (>5.5%) and myocardial triglycerides (>0.6%)
  • Elevated blood triglycerides >150mg/dL
  • Age < 50 years

Who cannot join

  • Type 2 Diabetes mellitus
  • Prior exposure to renin system blockers or HCTZ
  • BP > 160/100mmHg
  • Claustrophobia
  • Metallic implants in body
  • Pregnant or planning to become pregnant
  • Prior exposure to statin medications

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

Other trials in United States

About this study

Traditionally, obesity is considered an indirect cause of heart disease. Obese individuals typically present with a number of traditional Framingham risk factors (hypertension, dyslipidemia, and type 2 diabetes), predisposing them to heart attacks and subsequent heart failure. However, an emerging body of basic research revisits a hypothesis that fat is a direct cardiotoxin. Under healthy conditions, most triglyceride is stored in fatty tissue (adipocytes) while the amount of triglyceride stored in non-adipocyte tissues (such as the pancreas, the liver, skeletal muscle, and heart) is minimal and very tightly regulated. When this regulation is disrupted, intracellular triglyceride accumulates excessively in these organs ("steatosis") and has been implicated in activating adverse pathways which culminate in irreversible cell death ("lipotoxicity"), leading to several well-recognized clinical syndromes. These include non-alcoholic steatohepatitis (NASH), pancreatic beta-cell failure in type 2 diabetes, and dilated cardiomyopathy.

It has been recently observed that angiotensin II receptor blockers (ARBs) in addition to lowering blood pressure improve insulin sensitivity and decrease the risk for type 2 diabetes. This study will test the above theory in two study groups: Valsartan vs. Hydrochlorothiazide. We hypothesize that in obese humans with elevated myocardial triglycerides, blockade of the renin-angiotensin system (Valsartan group) will reduce myocardial fat with improvement of insulin sensitivity and heart function.

Read the detailed description

Basic science in animal models of genetic obesity have demonstrated that obese, insulin resistant animals have fatty hearts with reduced functional ability. More importantly, insulin sensitizing treatment of prediabetic rats delayed development of diabetes and improved heart function. A primary aim of our laboratory is to translate basic animal research, suggesting that excessive lipid accumulation in the myocardium is toxic, into the clinical setting using cardiac magnetic resonance imaging/spectroscopy technology. The results of this research may identify new biomarkers and drug targets to prevent cardiac disease in obese humans.

We used our novel in vivo magnetic resonance imaging and spectroscopy technique that enables quantification of triglyceride in human myocardium non-invasively, to demonstrate that obese humans like obese animals are characterized by elevated fat in myocardium. We hypothesize that in obese humans with elevated myocardial TG, blockade of the renin-angiotensin system will reduce myocardial fat with improvement of insulin sensitivity and heart function.

The aims of this study are to test if in obese people with impaired glucose tolerance (IGT):

Aim 1) Valsartan treatment will reduce myocardial fat and will improve heart geometry and function,

Aim 2) therapy with thiazide diuretic hydrochlorothiazide (HCTZ) treatment will elevate myocardial fat.

We are planning to test the action of Valsartan versus HCTZ as we expect that these drugs cause opposite metabolic effects. The landmark trial ALLHAT (Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial) has refocused attention to the thiazide-type diuretics as the first-line therapy for most patients with hypertension. Despite proven reduction in cardiovascular outcomes and low costs, there is on-going concern that one of the major side effect of the thiazides-glucose intolerance-may fuel the current U.S. epidemic of type 2 diabetes. Despite of efficacy and low cost thiazide diuretics are long known to cause insulin resistance, impaired glucose tolerance, and precipitation of overt diabetes.

Being tested
Valsartan, Hydrochlorothiazide
Keywords
Metabolic syndrome, Lipotoxicity, Insulin sensitivity, Myocardial triglyceride levels, Hepatic triglyceride levels, Magnetic resonance spectroscopy
Medical subject headings
Metabolic Syndrome, Insulin Resistance

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ValsartanDrug

    Also called Diovan

    Valsartan 320mg PO daily for 8 months

  • HydrochlorothiazideDrug

    Also called HCTZ

    Hydrochlorothiazide 25mg PO daily for 8 months

Study groups in NCT00745953
Study groupRoleWhat they receive
ValsartanActive comparatorThis arm will determine if blockade of the renin-angiotensin system reduces myocardial fat levels and improves insulin sensitivity. It consists of 6 visits: visit1 (baseline); visit2 (2 weeks); visit3 (1 month); visit4 (3 month); visit5 (6 month); visit6 (8 month). Visits 1 \& 6 will consist of blood tests, glucose tolerance test by FSivGTT, MRS, \& 24 hr ambulatory blood pressure monitoring. During visit 1, patients receive automatic blood pressure monitor, OMRON, to record blood pressure between visits. Visits 2 \& 3 are needed for the adjustment of medication to the final dose level. During visits 4 \& 5, Dr. Price will check subject's status as they continue the medication. In case of uncontrolled blood pressure, Dr. Price will prescribe amlodipine for the additional BP control.
Receives: Drug: Valsartan
HydrochlorothiazideActive comparatorThis arm will determine if thiazide diuretics elevate myocardial triglyceride levels. It consists of 6 visits: visit1 (baseline); visit2 (2 weeks); visit3 (1 month); visit4 (3 month); visit5 (6 month); visit6 (8 month). Visits 1 \& 6 will consist of blood tests, glucose tolerance test by FSivGTT, MRS, \& 24 hr ambulatory blood pressure monitoring. During visit 1, patients receive automatic blood pressure monitor, OMRON, to record blood pressure between visits. Visits 2 \& 3 are needed for the adjustment of medication to the final dose level. During visits 4 \& 5, Dr. Price will check subject's status as they continue the medication. In case of uncontrolled blood pressure, Dr. Price will prescribe amlodipine for the additional BP control.
Receives: Drug: Hydrochlorothiazide

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Myocardial triglyceride levels

    Measured: 8 months

Secondary outcomes (1)

  1. Hepatic triglyceride levels, insulin sensitivity, abdominal fat mass

    Measured: 8 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Sep 2008 (estimated)
  2. Study startAug 2007
  3. Primary completionAug 2009 (estimated)
  4. Study completionAug 2009 (estimated)

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00745953
Sponsor's protocol ID
IIRP Study US 73
Status last verified
Jan 2019
First submitted
29 Aug 2008
Last updated
17 Jan 2019
Results posted
No
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Valsartan and Hydrochlorothiazide in people with Metabolic Syndrome and Lipotoxicity, run by University of Texas Southwestern Medical Center 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 9 inclusion and 7 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: withdrawn, as of the sponsor's last update on 17 Jan 2019. 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.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

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?

Myocardial triglyceride levels (time frame: 8 months). 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 NCT00745953.

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 17 Jan 2019.

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