Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity (REVIVE)
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.
|Obesity Metabolic Syndrome X||Drug: Metformin Drug: Orlistat Drug: Topiramate Drug: Placebo||Phase 2|
|Study Design:||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?|
- 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.
- 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.
|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)|
|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||
Placebo pills and capsules for metformin, orlistat and topiramate
Please refer to this study by its ClinicalTrials.gov identifier: NCT01351753
|United States, Iowa|
|University of Iowa Hospitals and Clinics|
|Iowa City, Iowa, United States, 52241|
|Principal Investigator:||William G Haynes, MD||University of Iowa|