Comparison of the Effect of Intense-Exercise/Moderate-Calorie, Topiramate-Phentermine and Cognitive Behavioral Therapy on Obesity

This study has been withdrawn prior to enrollment.
(The project was not announced to the field and it was not funded.)
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT01970566
First received: August 28, 2013
Last updated: January 14, 2014
Last verified: January 2014
  Purpose

Obesity is a prevalent disorder and linked with inflammation, insulin resistance, dyslipidemia, obstructive sleep apnea, atherosclerosis, and associated with significant morbidity and mortality. This randomized clinical trial will compare the effectiveness of Intense Exercise/Moderate Calorie Restriction (IE-MCR), Topiramate-Phentermine (TP) and cognitive behavioral therapy (CBT) on obesity and atherosclerosis in individuals with morbidly obesity. This randomized clinical trial will compare: 1) the change in fat mass and atherosclerosis, 2) the change in psychological and quality-of-life as well as economic burden in response to IE-MCR, TP and CBT, and 3) conduct exploratory mechanistic biomolecular, genetic and therapeutic analyses to develop intervention-specific individualized intervention models to improve management of morbidly obese individuals.


Condition Intervention
Obesity
Diabetes Mellitus
Other: Behavioral and Drug
Other: Behavioral

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effect of Intense-Exercise/Moderate-Calorie vs Topiramate-Phentermine on Obesity

Resource links provided by NLM:


Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Compare the rate of change in fat mass in intense exercise/moderate diet restriction, topiramate-phentermine and cognitive behavior therapy [ Time Frame: 12 month and 24 month Follow Ups ] [ Designated as safety issue: No ]
    compare the change in extracellular/total body water, body fat/lean mass and metabolically active adipose tissue in response to IE-MCR vs. TP-CBT.


Secondary Outcome Measures:
  • Compare the rate of atherosclerotic burden in intense exercise/moderate diet restriction, topiramate-phentermine and cognitive behavior therapy [ Time Frame: 12 month and 24 month Follow Ups ] [ Designated as safety issue: No ]
    Compare the change in carotid intima media thickness, coronary artery distensibility index and plaque volume in response to IE-MCR,TP or CBT.

  • Compare the change in neuropsychiatric status in response to intense exercise/moderate diet restriction, topiramate-phentermine and cognitive behavioral therapy [ Time Frame: 12 month and 24 month Follow Ups ] [ Designated as safety issue: No ]
    compare the change in cognition, anxiety, depression and vitality in response to IE-MCR, TP and CBT.

  • Comparison the rate of and atherosclerotic burden in intense exercise/moderate diet restriction, topiramate-phentermine and cognitive behavior therapy [ Time Frame: 12 month and 24 month Follow Ups ] [ Designated as safety issue: No ]
    Compare the change in carotid intima media thickness, coronary artery distensibility index and plaque volume in response to IE-MCR,TP or CBT.

  • Compare the change in quality-of-life in response to intense exercise/moderate diet restriction, topiramate-phentermine and cognitive behavioral therapy [ Time Frame: 12 month and 24 month Follow Ups ] [ Designated as safety issue: No ]
    Compare the change in satisfaction, well-Being and quality of life in response to IE-MCR, TP and CBT


Enrollment: 0
Study Start Date: November 2013
Estimated Study Completion Date: November 2017
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: IE-MCR
Intense Exercise/Moderate Calorie Restriction
Other: Behavioral
Intense Exercise/Moderate Calorie Restriction
Other Name: IE-MCR
Active Comparator: TP-CBT
Topiramate-Phentermine plus cognitive behavioral therapy
Other: Behavioral and Drug
Topiramate-Phentermine plus cognitive behavioral therapy
Other Name: TP-CBT
Active Comparator: CBT
cognitive behavioral therapy
Other: Behavioral and Drug
Topiramate-Phentermine plus cognitive behavioral therapy
Other Name: TP-CBT
Other: Behavioral
Intense Exercise/Moderate Calorie Restriction
Other Name: IE-MCR

Detailed Description:

Background. Obesity is prevalent disorder; up to 60% of US population that is associated with significant morbidity and mortality through inflammation, insulin resistance, dyslipidemia, obstructive sleep apnea, and atherosclerosis. The economic burden of obesity-related illnesses is substantial, with estimates ranging from 2% to 7% of the total US health care expenditures and billions of dollars in direct and indirect costs to society. This randomized clinical trial will compared the effectiveness of Intense Exercise/Moderate Calorie Restriction (IE-MCR), Topiramate-Phentermine (TP) and cognitive behavioral therapy (CBT) on obesity and atherosclerosis in morbidly obesity individuals (body mass index(BMI)>40 kg/m2 or BMI>35 kg/m2 with associated comorbidities) with diabetes mellitus (DM).

Importance/Significance. There is a cumulative increase in the rate of obesity, up to 60% of the US population. This randomized clinical trial will compare: 1) the change in fat mass and atherosclerosis and, 2) the change in psychological status and quality-of-life as well as economic burden in response to IE-MCR, TP and CBT in morbidly obese individuals with DM. Furthermore, 3) exploratory analyses evaluating the different underling adipocyte molecular mechanisms will be conducted. This will investigate the underlying genomic determinants and characterizes the management of obesity by comparing biologic, clinical phenotype, and cost effectiveness of these two interventions. These aims will provide fundamental information to assess the beneficial effects within and across interventions on obesity and atherosclerosis management which will help provide individualized intervention models to improve management of morbidly obese individuals Method. A significant difference in reduction of fat mass, carotid/coronary atherosclerosis, improve in psychological, quality of life and economic burden measures, as well as exploratory mechanism of action across IE-MCR, TP and CBT methods, are hypothesized. Over a 5 year period, 60 morbidly obese individuals with diabetes mellitus aged 18 or older and free of clinical cardiovascular disease will be recruited from the Obesity Clinic of the Greater Los Angeles VA Health Care System, University of California Los Angeles and Captain Lovell Federal Healthcare Center. Eligible subjects will be randomized to either of intense exercise/moderate calorie restriction, Topiramate-Phentermine or cognitive behavioral therapy (20 in each group) and receive these intervention for 12-months. Intense exercise/moderate calorie restriction group will receive lectures on exercise and general dietary measures including calorie counting. They will prepare their own food, with protein:carbohydrate:fat ratio of 30:45:25 and over 70% of their resting daily energy expenditure (RDEE), and completed daily food and exercise journals. They will exercise ~2.5 hours/day, about 1/4 supervised, for a year. Topiramate-Phentermine group will receive full dose of TP (15/92mg) pills daily for a period of 1-year. Furthermore, CBT group as well as IE-MCR and TP will receive weekly cognitive behavior therapy for a year. All subjects will undergo carotid ultrasound; coronary computed tomography angiography, bioelectric impedance spectroscopy, dual-energy X-ray absorptiometry, ambulatory calorimetry, serial home resting metabolic rate serial home (RMR),sleep apnea assessment and abdominal fat pad fine-needle aspiration biopsy (FNAB), as well as measurement of oxidative stress/inflammatory/metabolic biomarkers at baseline and at 1-year follow-up. Quality of life, psychological health and economic burden will be assessed using standardized questionnaires. Participants will complete quarterly trial visits for physical exam, compliance to intervention as well as ascertainment of adverse effects.

  Eligibility

Ages Eligible for Study:   20 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 20-70 years
  • Competent to give informed consent
  • Obesity (BMI>40) or BMI>35 kg/m2 with associated co-morbidities
  • Diabetes Mellitus Type II

Exclusion Criteria:

  • History of coronary artery disease, myocardial infarction, coronary angioplasty or bypass surgery
  • Prior non-cardiac illness with an estimated life expectancy <4 years
  • Unable to give informed consent
  • Women who are pregnant or lactating
  • Prior bariatric surgery or receiving anti-obesity drugs
  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: NCT01970566

Locations
United States, Illinois
Captain James A. Lovell Federal Health Care Center, North Chicago, IL
North Chicago, Illinois, United States, 60064
Sponsors and Collaborators
Investigators
Principal Investigator: Naser Ahmadi, MD MS PhD Captain James A. Lovell Federal Health Care Center, North Chicago, IL
  More Information

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT01970566     History of Changes
Other Study ID Numbers: CLIN-001-12F
Study First Received: August 28, 2013
Last Updated: January 14, 2014
Health Authority: United States: Federal Government

Keywords provided by Department of Veterans Affairs:
Intense Exercise/Moderate Calorie Restriction
Topiramate-Phentermine

Additional relevant MeSH terms:
Diabetes Mellitus
Obesity
Body Weight
Endocrine System Diseases
Glucose Metabolism Disorders
Metabolic Diseases
Nutrition Disorders
Overnutrition
Overweight
Signs and Symptoms
Phentermine
Topiramate
Adrenergic Agents
Anti-Obesity Agents
Anticonvulsants
Appetite Depressants
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 29, 2014