Original Query: "Abdominal obesity metabolic syndrome"
Previous Study | Return to List | Next Study

Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity (REVIVE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01351753
Recruitment Status : Suspended (Change of staff)
First Posted : May 11, 2011
Last Update Posted : August 24, 2017
Information provided by (Responsible Party):
Gary L. Pierce, University of Iowa

Brief Summary:

Obesity is common (>30% of US adults), contributes to substantial morbidity and mortality, but is difficult to treat. Partly this is due to the transient, arduous and modest nature of lifestyle interventions. Partly it is due to the limited efficacy and safety problems of existing pharmacotherapy. Only one drug, orlistat, is approved for long-term use in obesity; but its effects on weight are relatively small. There are drugs that have been approved for other diseases but which also reduce weight. One promising approach to treating obesity is combination therapy with orlistat and one or more of these other agents. The investigators propose an innovative approach to developing new therapies for obesity coupling the use of combination therapy with rigorous assessment of cardiovascular safety. Vascular function is a quantitative surrogate clinical endpoint that has been strongly and independently linked to future cardiovascular events.

Our hypothesis is that combination pharmacotherapy will reduce weight and improve vascular function in obese human subjects. The co-primary endpoints will be weight and vascular function.

Condition or disease Intervention/treatment Phase
Obesity Metabolic Syndrome X Drug: Metformin Drug: Orlistat Drug: Topiramate Drug: Placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 150 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Does Reversal of Visceral Obesity by Drug Therapy Improve Vascular Function?
Study Start Date : March 2011
Estimated Primary Completion Date : October 2019
Estimated Study Completion Date : October 2019

Resource links provided by the National Library of Medicine

Drug Information available for: Orlistat
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Metformin Drug: Metformin
Experimental: Metformin + Orlistat Drug: Metformin Drug: Orlistat
Experimental: Metformin + Topiramate Drug: Metformin Drug: Topiramate
Experimental: Topiramate Drug: Topiramate
Experimental: Metformin + Topiramate + Orlistat Drug: Metformin Drug: Orlistat Drug: Topiramate
Placebo Comparator: Placebo Drug: Placebo
Placebo pills and capsules for metformin, orlistat and topiramate

Primary Outcome Measures :
  1. Weight (change from baseline) [ Time Frame: 12 months ]
    Weight obtained in the fasting state on a gowned subject.

  2. Brachial artery flow mediated dilatation (change from baseline) [ Time Frame: 12 months ]
    Conduit artery flow mediated dilatation (FMD) assessed using ultrasound-Doppler.

Secondary Outcome Measures :
  1. Number of subjects with mild, moderate and serious adverse events. [ Time Frame: 12 months ]
    Gastrointestinal, central nervous system, psychiatric, hepatic, renal, musculoskeletal and other adverse effects will be regularly assessed

  2. Systolic and diastolic systemic arterial pressure (change from baseline) [ Time Frame: 12 months ]
    Automated sphygmomanometry while sitting and 24-hour ambulatory BP monitoring.

  3. Fasting lipids, glucose and other biomarkers of obesity risk (change from baseline) [ Time Frame: 12 months ]
    Fasting total cholesterol, triglycerides, HDL-cholesterol, LDL-cholesterol, hsCRP, glucose, HBA1c, ALT, creatinine, eGFR, microalbuminuria, EKG voltage

  4. Mood, anxiety, quality of life and cognitive function (change from baseline) [ Time Frame: 12 months ]
    Mood assessed using Beck Depression Inventory. Anxiety assessed using Beck Anxiety Inventory. Quality of life assessed using SF-36 and IWQOL surveys. Cognition assessed using Trail Making A & B, Controlled Oral Word Association, and Letter-Number Sequencing Tests.

  5. Body fat distribution (change from baseline) [ Time Frame: 12 months ]
    Body fat distribution measured using anthropometry (waist, neck and hip circumferences), as well as air displacement plethysmography, electrical bioimpedance, and DEXA in subsets of subjects.

  6. Pulse wave velocity (PWV) and aortic augmentation pressure (change from baseline) [ Time Frame: 12 months ]
    Carotid-femoral pulse wave velocity and estimated aortic augmentation pressure measured using pulse tonometry (Sphygmocor).

  7. Peripheral arteriolar tonometry [ Time Frame: 12 months ]
    Reactive hyperemia in finger tip measured using EndoPAT.

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Ages Eligible for Study:   40 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 40 to 75 years
  • Male or postmenopausal female
  • BMI ≥ 30 kg/m2
  • One or more major cardiovascular (CV) risk factors (hypertension, dyslipidemia, impaired glucose tolerance OR metabolic syndrome)

Exclusion Criteria:

  • Congestive heart failure
  • Renal impairment
  • History of bariatric surgery (i.e. lap-band, Roux-en-Y or biliopancreatic diversion)
  • Type I diabetes mellitus
  • Weight loss > 10% in the past 6 months
  • Recurrent nephrolithiasis
  • Current treatment for seizure disorder
  • Hepatic cirrhosis
  • Current use of study medications
  • Current use of oral estrogen
  • History of smoking cessation in the past three months
  • Current cholestasis or malabsorption syndrome
  • Planned use of any herbal or over-the-counter supplements for weight loss
  • History of allergic reactions to metformin, topiramate, orlistat or any of ingredients
  • Medical conditions requiring continuous use of phosphodiesterase inhibitors and/or the inability to withhold phosphodiesterase inhibitors for 48 hours
  • Participation in another clinical drug study within four weeks prior to this investigation.
  • Participation in any other weight loss or rigorous exercise program.
  • Any disease or condition that in the opinion of the investigator may interfere with completion of the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01351753

United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52241
Sponsors and Collaborators
University of Iowa
Principal Investigator: Gary L Pierce, PhD University of Iowa

Additional Information:
Responsible Party: Gary L. Pierce, Associate Professor, University of Iowa Identifier: NCT01351753     History of Changes
Other Study ID Numbers: 201012738
First Posted: May 11, 2011    Key Record Dates
Last Update Posted: August 24, 2017
Last Verified: August 2017

Keywords provided by Gary L. Pierce, University of Iowa:
Metabolic Syndrome X
Impaired glucose tolerance

Additional relevant MeSH terms:
Metabolic Syndrome X
Nutrition Disorders
Body Weight
Signs and Symptoms
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Hypoglycemic Agents
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Anti-Obesity Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action