Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity | RxWiki

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

Overview[ - collapse ][ - ]

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	Obesity Metabolic Syndrome X
Intervention	Drug: Metformin Drug: Orlistat Drug: Topiramate Drug: Placebo
Phase	Phase 2
Sponsor	University of Iowa
Responsible Party	University of Iowa
ClinicalTrials.gov Identifier	NCT01351753
First Received	May 4, 2011
Last Updated	April 16, 2012
Last verified	April 2012

Tracking Information[ + expand ][ + ]

First Received Date	May 4, 2011
Last Updated Date	April 16, 2012
Start Date	March 2011
Estimated Primary Completion Date	December 2013
Current Primary Outcome Measures	Weight (change from baseline) [Time Frame: 12 months] [Designated as safety issue: No]Weight obtained in the fasting state on a gowned subject. Brachial artery flow mediated dilatation (change from baseline) [Time Frame: 12 months] [Designated as safety issue: No]Conduit artery flow mediated dilatation (FMD) assessed using ultrasound-Doppler.
Current Secondary Outcome Measures	Number of subjects with mild, moderate and serious adverse events. [Time Frame: 12 months] [Designated as safety issue: Yes]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] [Designated as safety issue: No]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] [Designated as safety issue: No]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] [Designated as safety issue: Yes]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] [Designated as safety issue: No]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] [Designated as safety issue: No]Carotid-femoral pulse wave velocity and estimated aortic augmentation pressure measured using pulse tonometry (Sphygmocor). Peripheral arteriolar tonometry [Time Frame: 12 months] [Designated as safety issue: No]Reactive hyperemia in finger tip measured using EndoPAT.

Descriptive Information[ + expand ][ + ]

Brief Title	Drug Therapy Induced Weight Loss to Improve Blood Vessel Function in Subjects With Obesity
Official Title	Does Reversal of Visceral Obesity by Drug Therapy Improve Vascular Function?
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.
Detailed Description	Not Provided
Study Type	Interventional
Study Phase	Phase 2
Study Design	Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Condition	Obesity Metabolic Syndrome X
Intervention	Drug: Metformin Drug: Orlistat Drug: Topiramate Drug: Placebo Placebo pills and capsules for metformin, orlistat and topiramate
Study Arm (s)	Active Comparator: Metformin Experimental: Metformin + Orlistat Experimental: Metformin + Topiramate Experimental: Topiramate Experimental: Metformin + Topiramate + Orlistat Placebo Comparator: Placebo

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	150
Estimated Completion Date	December 2013
Estimated Primary Completion Date	November 2013
Eligibility 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
Gender	Both
Ages	40 Years
Accepts Healthy Volunteers	No
Contacts	Contact: William G Haynes, MD revive@uiowa.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01351753
Other Study ID Numbers	UI 201012738
Has Data Monitoring Committee	No
Information Provided By	University of Iowa
Study Sponsor	University of Iowa
Collaborators	Not Provided
Investigators	Principal Investigator: William G Haynes, MD University of Iowa
Verification Date	April 2012

Locations[ + expand ][ + ]

University of Iowa Hospitals and Clinics	Iowa City, Iowa, United States, 52241 Contact: Graziela Kalil, Pharm.D. \| 319-356-2710 \| graziela-kalil@uiowa.edu Principal Investigator: William G Haynes, MD Recruiting