ObesityPhase 4NCT00675987

A Randomized Clinical Trial To Study Losartan On Endothelial Dysfunction and Insulin Resistance In Obese Patients

A Phase 4 study testing losartan in people with Obesity and Hypertension, run by Brigham and Women's Hospital at 9 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The main purposes of this study are to find out if the study drug losartan (Cozaar) or placebo ("sugar pill") has an effect on insulin sensitivity (how your body responds to insulin) and to measure the effect of the study drug losartan or placebo on how the arteries in your arm dilate (enlarge to carry more blood). Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Obesity, Hypertension, Hyperglycemia
What is being tested?: losartan
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 53 participants
Where: 9 sitesUnited States
Study dates: May 2007to Dec 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

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 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Currently taking 1 or no antihypertensive medication
Male and female between 18 and 75 years of age
Mean trough sitting diastolic blood pressure (SiDBP) ≥80 and < 100 mm Hg
Mean trough sitting systolic blood pressure (SiSBP) ≥120 and <160 mm Hg
Non-diabetic patients with fasting plasma glucose ≥100 mg/dL and <126 mg/dL
Body mass index (BMI) >30 and <40
Waist circumference >40 inches in males, > 35 inches in females
A patient who is of reproductive potential and agrees to remain abstinent or use acceptable methods of birth control (intrauterine device (IUD), diaphragm with spermicide, contraceptive sponge, condom, hormonal contraception, vasectomy) within the projected duration of the study

Who cannot join

Secondary hypertension of any etiology (renal artery stenosis, coarctation of the aorta or pheochromocytoma, hypertension induced by oral contraceptives)
History of malignant hypertension
Any clinically significant renal disease including single functioning kidney, and known history of anuria. Any severe renal impairment, as manifested by serum creatinine more than 1.5 mg/dL, or proteinuria >2+ by urine dipstick
Known sensitivity or intolerance to angiotensin II receptor antagonists
Type I or II diabetes
Inability or unwillingness to abstain from taking prohibited medications during the study period

Show all 25Show fewer

History of myocardial infarction (MI), percutaneous coronary intervention (PCI), coronary artery bypass graft (CABG), congestive heart failure (CHF), unstable angina, transient ischemic attack (TIA), or cerebrovascular accident (CVA)
Concomitant cardiac conditions that would make it unsafe to participate in the trial (e.g., clinically significant atrioventricular (AV) conduction disturbance, atrial flutter, atrial fibrillation, potentially life-threatening ventricular arrhythmias, decompensated valvular disease, presence of hemodynamically significant obstructive valvular disease, or cardiomyopathy)
History of angioedema and/or organ damage from hypertension
Serum potassium < 3.5 or > 5.5 mEq/L
Any clinically significant laboratory value which in the investigator's judgment could be clinically significant to the outcome of this study.
History of clinically important gastrointestinal resection or malabsorption
Patient with a history or current evident of any condition, therapy, lab abnormality, or other circumstance that might confound the results of the study, or interfere with the patient's participation for the full duration of the study, such that it is not in the best interest of the patient to participate. (Including but not limited to: recent or current alcoholism, drug abuse within the prior 2 years, mental or legal incapacitation, any disease which could reasonably be expected to be fatal or life-threatening, or a history of malignancy ≤ 5 years prior to signing informed consent.)
Currently participating or has participated in a study with an investigational compound or device within 30 days of signing informed consent.
Inability to be taken off all current antihypertensive medication and placed on placebo for up to 12 weeks.
Unwillingness or unlikely to adhere to the study procedures, keep appointments, or is planning to relocate during the study.
Arm circumference great than 52 cm
Smokers or former smokers who have quite less than 1 year prior to Visit 1
Anemia (Hemoglobin < 11)
Allergy to latex
Deformed hands and/or fingers that would interfere with the collection of pulse volume amplitude measurements
History of Raynaud's disease or any other vascular condition
Bilateral mastectomy
Aortic stenosis
Patient is taking high doses of antioxidant supplements (vitamins, minerals, or other)

Trial locations and contacts

9 sites in 1 country.

City, postcode or hospital

9 sites in 1 country

United States9 sites

Brigham and Women's Hospital Cardiovascular Division
Boston, Massachusetts, 02115
University of Texas SW Medical Center at Dallas
Dallas, Texas, 75390
Hypertension Clinical Pharmacology Baylor Clinic
Houston, Texas, 77030
Indiana University School of Medicine
Indianapolis, Indiana, 46202
CAVS Clinical Research Center
Little Rock, Arkansas, 72205
University of Miami Diabetes Research Institute
Miami, Florida, 33136
St. Lukes Roosevelt Hospital
New York, New York, 10025
University of Pennsylvania School of Medicine
Philadelphia, Pennsylvania, 19104
VA San Diego Health Care System
San Diego, California, 92161

Other trials in United States

About this study

Official title: Protocol Merck 318-00: A Double-Blind, Placebo-Controlled, Randomized, Parallel, Clinical Trial To Study The Effect Of Losartan Potassium On Endothelial Dysfunction And Insulin Resistance In Obese Patients With Impaired Fasting Glucose

We hope to learn if taking losartan changes the amount of certain proteins in the blood that effect blood vessel function.

Losartan is approved by the US FDA to treat high blood pressure. It will take approximately 4 months for you to complete this study.

Conditions: Obesity, Hypertension, Hyperglycemia
Being tested: losartan, Placebo control
Keywords: Impaired Fasting Glucose FPG >100-<126 mg/dL
Medical subject headings: Obesity, Hypertension, Hyperglycemia

What participants receive

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

losartanDrug
Also called Cozaar
losartan 100 mg tablets 1 tab po QD
Placebo controlDrug
Placebo 1 po QD

Study groups in NCT00675987
Study group	Role	What they receive
Losartan	Active comparator	Losartan 100 mg 1 tab po QD Receives: Drug: losartan
Placebo	Placebo comparator	Placebo 1 tab po QD Receives: Drug: Placebo control

What is being measured

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

Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp
Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level.
Measured: baseline, 8 weeks
Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude
Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus.
Measured: baseline, 8 weeks

Secondary outcomes (7)

Change in Urine Albumin/Creatine
Urine was obtained to assess for the presence of microalbuminuria.
Measured: baseline, 8 weeks
Change in hsCRP (High-sensitivity C-reactive Protein)
hsCRP (high-sensitivity C-reactive protein) is a marker of inflammation
Measured: baseline, 8 weeks
Change in VCAM-1(Vascular Cell-adhesion Molecule-1)
VCAM-1 is an immunoglobulin-like adhesion molecule expressed on activated endothelial cells.
Measured: baseline, 8 weeks
Change in MCP-1 (Monocyte Chemoattractant Protein-1)
MCP-1 is one of the key chemokines that regulate migration and infiltration of monocytes/macrophages.
Measured: baseline, 8 weeks
Change in Ox-LDL (Oxidized Low-density Lipoprotein)
ox-LDL measures protein damage due to the oxidative modification of the ApoB subunit on LDL cholesterol.
Measured: baseline, 8 weeks
Change in F2-isoprostanes
F2-isoprostanes is a marker of oxidative stress.
Measured: baseline, 8 weeks
Change in E-selectin
E-selectin is expressed on inflamed endothelial cells in response to treatment with inflammatory cytokines.
Measured: baseline, 8 weeks

Timeline

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

May 2007Dec 2008

First posted12 May 2008 (estimated)
Study startMay 2007
Primary completionDec 2008
Study completionDec 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for ObesityStudies 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 4
Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 53 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00675987
Sponsor's protocol ID: 2007-P-000490
Status last verified: Aug 2018
First submitted: 8 May 2008
Last updated: 6 Sep 2018
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

Perlstein TS, Henry RR, Mather KJ, Rickels MR, Abate NI, Grundy SM, Mai Y, Albu JB, Marks JB, Pool JL, Creager MA. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin Sci (Lond). 2012 Feb;122(4):193-202. doi: 10.1042/CS20110284.
PubMed 21861845

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 6 Sep 2018. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Protocol Merck 318-00: A Double-Blind, Placebo-Controlled, Randomized, Parallel, Clinical Trial To Study The Effect Of Losartan Potassium On Endothelial Dysfunction And Insulin Resistance In Obese Patients With Impaired Fasting Glucose
ClinicalTrials.gov ID: NCT00675987
Acronym / sponsor ID: 2007-P-000490
Conditions: Obesity, Hypertension, Hyperglycemia
Keywords: Impaired Fasting Glucose FPG >100-<126 mg/dL
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 53 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Collaborators: Merck Sharp & Dohme LLC
Study start: May 2007
Primary completion: Dec 2008 (actual)
Study completion: Dec 2008 (actual)
First posted: 12 May 2008 (estimated)
Results: Posted 21 Aug 2012

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

We hope to learn if taking losartan changes the amount of certain proteins in the blood that effect blood vessel function.

Losartan is approved by the US FDA to treat high blood pressure. It will take approximately 4 months for you to complete this study.

Study design

Primary purpose: Other
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Losartan	Active comparator	Drug: losartanLosartan 100 mg 1 tab po QD
Placebo	Placebo comparator	Drug: Placebo controlPlacebo 1 tab po QD

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Currently taking 1 or no antihypertensive medication
Male and female between 18 and 75 years of age
Mean trough sitting diastolic blood pressure (SiDBP) ≥80 and < 100 mm Hg
Mean trough sitting systolic blood pressure (SiSBP) ≥120 and <160 mm Hg
Non-diabetic patients with fasting plasma glucose ≥100 mg/dL and <126 mg/dL

Key exclusion criteria (25 listed)

Secondary hypertension of any etiology (renal artery stenosis, coarctation of the aorta or pheochromocytoma, hypertension induced by oral contraceptives)
History of malignant hypertension
Any clinically significant renal disease including single functioning kidney, and known history of anuria. Any severe renal impairment, as manifested by serum creatinine more than 1.5 mg/dL, or proteinuria >2+ by urine dipstick
Known sensitivity or intolerance to angiotensin II receptor antagonists
Type I or II diabetes

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
losartanAlso: Cozaarlosartan 100 mg tablets 1 tab po QD	Drug	Losartan
Placebo controlPlacebo 1 po QD	Drug	Placebo

Primary outcome

Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp
Time frame: baseline, 8 weeks
Insulin clamp derived insulin sensitivity, as insulin stimulated glucose disposal corrected for steady state insulin level.
Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude
Time frame: baseline, 8 weeks
Endothelial function assessed as the ratio of pulse volume amplitude after compared with before a reactive hyperemia stimulus, measured by peripheral (fingertip) arterial tonometry. Reported values indicate the percentage change from Baseline in the ratio of pulse volume amplitude after compared to before the reactive hyperemia stimulus.

7 secondary outcomes

Change in Urine Albumin/Creatine
Time frame: baseline, 8 weeks
Change in hsCRP (High-sensitivity C-reactive Protein)
Time frame: baseline, 8 weeks
Change in VCAM-1(Vascular Cell-adhesion Molecule-1)
Time frame: baseline, 8 weeks
Change in MCP-1 (Monocyte Chemoattractant Protein-1)
Time frame: baseline, 8 weeks
Change in Ox-LDL (Oxidized Low-density Lipoprotein)
Time frame: baseline, 8 weeks
Change in F2-isoprostanes
Time frame: baseline, 8 weeks
Change in E-selectin
Time frame: baseline, 8 weeks

Results and safety

Results posted to the registry on 21 Aug 2012, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Losartan 100 mg 1 Tab po QD	26	26
Placebo 1 Tab po QD	27	27

Primary outcome: Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp

Time frame: baseline, 8 weeks. Mean (Standard Deviation). Unit: mg/kg/min

Measure	Placebo n = 27	Losartan n = 26
Value	5.3 (4.5)	2.8 (1.7)

Population analysed: analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded)

Primary outcome: Insulin Sensitivity Utilizing Endothelial Function as Assessed by Pulse Volume Amplitude

Time frame: baseline, 8 weeks. Mean (Standard Deviation). Unit: percentage change

Measure	Placebo n = 27	Losartan n = 26
Value	1.76 (0.7)	2.11 (0.7)

Population analysed: analysis was ITT, but limited to those with interpretable data (3 clamp studies were excluded)

7 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Losartan	0 of 26 (0%)	0 of 26 (0%)	Not reported
Placebo	0 of 27 (0%)	0 of 27 (0%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 6 Sep 2018.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Results publication: PubMed 21861845Perlstein TS, Henry RR, Mather KJ, Rickels MR, Abate NI, Grundy SM, Mai Y, Albu JB, Marks JB, Pool JL, Creager MA. Effect of angiotensin receptor blockade on insulin sensitivity and endothelial function in abdominally obese hypertensive patients with impaired fasting glucose. Clin Sci (Lond). 2012 Feb;122(4):193-202. doi: 10.1042/CS20110284.

Related trials for Obesity

RecruitingPhase 4
Translational Health Research Into Vascular and Neurocognitive Effects of Weight Loss
Class I/II Obesity
Not yet recruitingObservational study
Assessing the Impact of Perceptions of Unpredictability on Objective Measures of Food Consumption and Metabolism
Healthy Volunteer, Obestity
RecruitingPhase 1/2
A Phase 1/2a Study of WVE-007 in Adults Living With Overweight or Obesity
Overweight and Obesity
Not yet recruitingPhase 4
Effects of Tirzepatide on Esophagogastric Junction Mechanics, Reflux Burden, and Gastric Physiology in Adults With Obesity
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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.

Mark A Creager, MD principal investigator

Brigham and Women's Hospital

9 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing losartan in people with Obesity and Hypertension, run by Brigham and Women's Hospital at 9 sites 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 8 inclusion and 25 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 6 Sep 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 9 sites 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.

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?

Yes. Results are posted in the registry (first posted 21 Aug 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

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?

Insulin Sensitivity Utilizing the Euglycemic Hyperinsulinemic Clamp (time frame: baseline, 8 weeks). The study lists 2 primary outcomes in all. 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 NCT00675987, 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 6 Sep 2018.