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

Does Reversal of Visceral Obesity by Drug Therapy Improve Vascular Function?

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.

Study Overview

• Status: Terminated
• Conditions: Obesity; Metabolic Syndrome X
• Intervention / Treatment: Drug: Topiramate; Drug: Metformin; Drug: Orlistat; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 136
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Iowa
    • Iowa City, Iowa, United States, 52241
      • University of Iowa Hospitals and Clinics

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

6

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Weight (% Change From Baseline)	Weight obtained in the fasting state on a gowned subject.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Office Systolic Blood Pressure (mmHg Change From Baseline)	Automated sphygmomanometry while sitting	6 months
Waist (cm Change After 6 Months From Baseline)	Body fat distribution measured using anthropometry (waist, neck and hip circumferences)	6 months
Carotid-femoral Pulse Wave Velocity (PWV)(Change After 6 Months From Baseline)	Change in carotid-femoral pulse wave velocity (Sphygmocor).	6 months

Collaborators and Investigators

• Sponsor: University of Iowa

Publications and helpful links

Helpful Links

• Recruitment website

Study record dates

Study Major Dates

• Study Start (Actual): March 1, 2011
• Primary Completion (Actual): January 9, 2014
• Study Completion (Actual): January 9, 2014

Study Registration Dates

• First Submitted: May 4, 2011
• First Submitted That Met QC Criteria: May 9, 2011
• First Posted (Estimate): May 11, 2011

Study Record Updates

• Last Update Posted (Actual): June 9, 2021
• Last Update Submitted That Met QC Criteria: May 13, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: Obesity; Dyslipidemia; Hypertension; Impaired glucose tolerance; Metabolic Syndrome X
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Insulin Resistance; Hyperinsulinism; Angina Pectoris; Obesity; Metabolic Syndrome; Microvascular Angina; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Lipid Regulating Agents; Anticonvulsants; Anti-Obesity Agents; Metformin; Topiramate; Orlistat
• Other Study ID Numbers: 201012738