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

NCT01351753 | Terminated Phase 2 Results

• 1 other identifier: 201012738
• Study Type: interventional
• Target: 128
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Metabolic Syndrome X

Keywords

Obesity; Metabolic Syndrome X; Hypertension; Dyslipidemia; Impaired glucose tolerance

Outcome Measures

Primary Outcomes (1)

• Weight (Percent Change From Baseline)

  Weight obtained in the fasting state on a gowned subject.

  Baseline and 6 months

Secondary Outcomes (3)

• Office Systolic Blood Pressure (mmHg Change From Baseline)

  Baseline and 6 months

• Centimeter Change in Waist Circumference

  Baseline and 6 months

• Carotid-femoral Pulse Wave Velocity (PWV)(Change After 6 Months From Baseline)

  Baseline and 6 months

Study Arms (6)

Metformin

ACTIVE COMPARATOR

Drug: Metformin

Metformin + Orlistat

EXPERIMENTAL

Drug: Metformin; Drug: Orlistat

Metformin + Topiramate

EXPERIMENTAL

Drug: Metformin; Drug: Topiramate

Topiramate

EXPERIMENTAL

Drug: Topiramate

Metformin + Topiramate + Orlistat

EXPERIMENTAL

Drug: Metformin; Drug: Orlistat; Drug: Topiramate

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Orlistat DRUG

Metformin + Orlistat; Metformin + Topiramate + Orlistat

Topiramate DRUG

Metformin + Topiramate; Metformin + Topiramate + Orlistat; Topiramate

Placebo DRUG

Placebo pills and capsules for metformin, orlistat and topiramate

Placebo

Metformin DRUG

Metformin; Metformin + Orlistat; Metformin + Topiramate; Metformin + Topiramate + Orlistat

Eligibility Criteria

• Age: 40 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Iowa: lead

Study Sites (1)

University of Iowa Hospitals and Clinics

Iowa City, Iowa, 52241, United States

Location

Related Links

• Recruitment website

MeSH Terms

Conditions

Obesity; Metabolic Syndrome; Hypertension; Dyslipidemias; Glucose Intolerance

Interventions

Metformin; Orlistat; Topiramate

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Insulin Resistance; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Vascular Diseases; Cardiovascular Diseases; Lipid Metabolism Disorders; Hyperglycemia

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Lactones; Fructose; Hexoses; Monosaccharides; Sugars; Carbohydrates; Ketoses

Results Point of Contact

• Title: Gary Pierce, PhD
• Organization: University of Iowa

gary-pierce@uiowa.edu

13193359487

Study Officials

• Gary L Pierce, PhD

  University of Iowa

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 4, 2011
• First Posted: May 11, 2011
• Study Start: March 1, 2011
• Primary Completion: January 9, 2014
• Study Completion: January 9, 2014
• Last Updated: March 12, 2026
• Results First Posted: June 9, 2021

Record last verified: 2026-02

Locations

US (1)