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

This study has suspended participant recruitment.
(Change of staff)
Sponsor:
Information provided by (Responsible Party):
William G. Haynes, University of Iowa
ClinicalTrials.gov Identifier:
NCT01351753
First received: May 4, 2011
Last updated: March 1, 2017
Last verified: March 2017
  Purpose

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 Intervention Phase
Obesity
Metabolic Syndrome X
Drug: Metformin
Drug: Orlistat
Drug: Topiramate
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator, Outcomes Assessor
Primary Purpose: Treatment
Official Title: Does Reversal of Visceral Obesity by Drug Therapy Improve Vascular Function?

Resource links provided by NLM:


Further study details as provided by University of Iowa:

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

  • 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:
  • 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

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

  • 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

  • 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.

  • 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.

  • 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).

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


Estimated Enrollment: 150
Study Start Date: March 2011
Estimated Study Completion Date: October 2019
Estimated Primary Completion Date: October 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

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

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01351753

Locations
United States, Iowa
University of Iowa Hospitals and Clinics
Iowa City, Iowa, United States, 52241
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: William G Haynes, MD University of Iowa
  More Information

Additional Information:
Responsible Party: William G. Haynes, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01351753     History of Changes
Other Study ID Numbers: 201012738
Study First Received: May 4, 2011
Last Updated: March 1, 2017

Keywords provided by University of Iowa:
Obesity
Metabolic Syndrome X
Hypertension
Dyslipidemia
Impaired glucose tolerance

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

ClinicalTrials.gov processed this record on April 21, 2017