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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified April 2012 by University of Iowa.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
William G. Haynes, University of Iowa
ClinicalTrials.gov Identifier:
NCT01351753
First received: May 4, 2011
Last updated: April 16, 2012
Last verified: April 2012
  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
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ 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.


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.


Estimated Enrollment: 150
Study Start Date: March 2011
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: November 2013 (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
Genders Eligible for Study:   Both
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

Contacts
Contact: William G Haynes, MD revive@uiowa.edu

Locations
United States, Iowa
University of Iowa Hospitals and Clinics Recruiting
Iowa City, Iowa, United States, 52241
Contact: Graziela Kalil, Pharm.D.    319-356-2710    graziela-kalil@uiowa.edu   
Principal Investigator: William G Haynes, MD         
Principal Investigator: Graziela Z Kalil, PharmD         
Sponsors and Collaborators
University of Iowa
Investigators
Principal Investigator: William G Haynes, MD University of Iowa
  More Information

Additional Information:
No publications provided

Responsible Party: William G. Haynes, Professor, University of Iowa
ClinicalTrials.gov Identifier: NCT01351753     History of Changes
Other Study ID Numbers: UI 201012738
Study First Received: May 4, 2011
Last Updated: April 16, 2012
Health Authority: United States: Institutional Review Board

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
Orlistat
Topiramate
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Obesity Agents
Central Nervous System Agents
Therapeutic Uses
Anticonvulsants
Neuroprotective Agents
Protective Agents

ClinicalTrials.gov processed this record on August 28, 2014