Effect of Caloric Restriction on Fat Oxidation in Obese Men and Women (Magellan II)

This study has been completed.
Sponsor:
Collaborator:
Takeda
Information provided by (Responsible Party):
Translational Research Institute for Metabolism and Diabetes, Florida
ClinicalTrials.gov Identifier:
NCT01616082
First received: June 4, 2012
Last updated: December 5, 2012
Last verified: December 2012
  Purpose

The purpose of this study is to better understand the different ways our bodies burn fat which may be important for obesity, diabetes, and cardiovascular disease.


Condition Intervention
Obesity
Overweight
Metabolic Diseases
Behavioral: Low Calorie Diet (LCD)
Drug: Phentermine

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Effect of Caloric Restriction on Metabolic Biomarkers and Fat Oxidation in Obese Men and Women (Magellan II)

Resource links provided by NLM:


Further study details as provided by Translational Research Institute for Metabolism and Diabetes, Florida:

Primary Outcome Measures:
  • Change from baseline amount of fat oxidation at 14 days [ Time Frame: Days 0, 14 ] [ Designated as safety issue: No ]

    Measurements will be taken from Biopsy

    Expected Results

    • Overweight and obese subjects will show a wide variation in fat oxidation in response to the low calorie diet
    • Approximately one-third of study participants will not meet target weight loss by four weeks
    • Following an overnight fast (prior to and during LCD) individuals that fail to meet the target weight loss will be characterized by decreased whole body fat oxidation and increased carbohydrate oxidation (measured by indirect calorimetry)

  • Change from baseline amount of fat oxidation at 1 week intervals [ Time Frame: Days 0, 7, 14, 28, 49, 56 ] [ Designated as safety issue: No ]

    Measurements will be taken from resting metabolic rate (RMR)

    Expected Results

    • Overweight and obese subjects will show a wide variation in fat oxidation in response to the low calorie diet
    • Approximately one-third of study participants will not meet target weight loss by four weeks
    • Following an overnight fast (prior to and during LCD) individuals that fail to meet the target weight loss will be charaterized by decreased whole body fat oxidation and increased carbohydrate oxidation (measured by indirect calorimetry)


Secondary Outcome Measures:
  • Change in area of hepatic lipid and skeletal muscle IMCL content [ Time Frame: Days -7, -1, 14, 56 ] [ Designated as safety issue: No ]

    Masured with magnetic resonance spectroscopy (MRS)

    Expected results

    • 1H-MRS can measure hepatic lipid and skeletal muscle (intramyocellular lipid) IMCL content with low test-retest variability
    • 1H-MRS can sensitively monitor reductions (or lack thereof) in skeletal muscle IMCL and liver intrahepatocellular lipid (IHCL) concentration during caloric restriction
    • Reductions in IMCL and IHCL will be higher in subjects with lower fasting respiratory quotients (RQ) at baseline/during LCD

  • Frequency of presence of serum biomarkers at baseline [ Time Frame: Day 0 ] [ Designated as safety issue: No ]

    Expected results

    - One or more of the measured parameters will emerge as biomarkers of low fat oxidation


  • Frequency of presence of serum biomarkers at 14 days [ Time Frame: Day 14 ] [ Designated as safety issue: No ]

    Expected results

    - One or more of the measured parameters will emerge as biomarkers of low fat oxidation



Enrollment: 45
Study Start Date: September 2011
Study Completion Date: November 2012
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Overweight, no drug
After screening, overweight (BMI 27.0 - 30.0, inclusive) subjects will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved.
Behavioral: Low Calorie Diet (LCD)
A Diet History Questionnaire will be completed, and the subjects will have dietary counseling and be provided shakes. The low calorie diet will begin, to continue for a period of 8 weeks.
Active Comparator: Obese with no drug
After screening, overweight (obese subjects (BMI ≥30 - ≤40.0) subjects (n=35) will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved. Individuals not on track to achieve their target weight by four weeks will receive the drug Phentermine to promote weight loss. Then, following eight weeks LCD (or four weeks LCD + four weeks LCD+Phentermine), in the event that they did not achieve the target weight loss, subjects will be given the option to continue with the LCD + Phentermine for up to an additional 12 weeks, under a doctor's supervision.
Behavioral: Low Calorie Diet (LCD)
A Diet History Questionnaire will be completed, and the subjects will have dietary counseling and be provided shakes. The low calorie diet will begin, to continue for a period of 8 weeks.
Placebo Comparator: Overweight with Phentermine
After screening, overweight (BMI 27.0 - 30.0, inclusive) subjects will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved. Individuals not on track to achieve their target weight by four weeks will receive the drug Phentermine to promote weight loss. Then, following eight weeks LCD (or four weeks LCD + four weeks LCD+Phentermine), in the event that they did not achieve the target weight loss, subjects will be given the option to continue with the LCD + Phentermine for up to an additional 12 weeks, under a doctor's supervision.
Behavioral: Low Calorie Diet (LCD)
A Diet History Questionnaire will be completed, and the subjects will have dietary counseling and be provided shakes. The low calorie diet will begin, to continue for a period of 8 weeks.
Drug: Phentermine

Individuals not on track to achieve their target weight by four weeks will receive the drug Phentermine to promote weight loss. Then, following eight weeks LCD (or four weeks LCD + four weeks LCD+Phentermine), in the event that they did not achieve the target weight loss, subjects will be given the option to continue with the LCD + Phentermine for up to an additional 12 weeks, under a doctor's supervision.

Protection Against Risk:

  • Prior to administering any phentermine, a history and physical including EKG will be conducted (at the screening visit) and will be used to determine whether the participant is clear to receive the medication.
  • Participants will see the study doctor or nurse practitioner at every study visit after the drug is initiated.
Placebo Comparator: Obese with Phentermine
After screening, obese subjects (BMI ≥30 - ≤40.0) subjects (n=35) will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved. Individuals not on track to achieve their target weight by four weeks will receive the drug Phentermine to promote weight loss. Then, following eight weeks LCD (or four weeks LCD + four weeks LCD+Phentermine), in the event that they did not achieve the target weight loss, subjects will be given the option to continue with the LCD + Phentermine for up to an additional 12 weeks, under a doctor's supervision.
Behavioral: Low Calorie Diet (LCD)
A Diet History Questionnaire will be completed, and the subjects will have dietary counseling and be provided shakes. The low calorie diet will begin, to continue for a period of 8 weeks.
Drug: Phentermine

Individuals not on track to achieve their target weight by four weeks will receive the drug Phentermine to promote weight loss. Then, following eight weeks LCD (or four weeks LCD + four weeks LCD+Phentermine), in the event that they did not achieve the target weight loss, subjects will be given the option to continue with the LCD + Phentermine for up to an additional 12 weeks, under a doctor's supervision.

Protection Against Risk:

  • Prior to administering any phentermine, a history and physical including EKG will be conducted (at the screening visit) and will be used to determine whether the participant is clear to receive the medication.
  • Participants will see the study doctor or nurse practitioner at every study visit after the drug is initiated.

Detailed Description:

In this study the investigators will examine the hypothesis that overweight/obese individuals that are unable to meet target weight loss goals on a low calorie diet (LCD) are intrinsically less metabolically flexible than their weight-losing counterparts. The investigators expect that this 'inflexibility' will be characterized by impaired fat oxidation (as determined by indirect calorimetry) in response to caloric restriction. If this were the case, these subjects may represent a population of 'super-responders' likely to demonstrate a robust response to approaches to increase fat oxidation. The investigators will also measure lipid concentrations in skeletal muscle and liver by hydrogen 1 magnetic resonance (1H-MRS) to determine both the stability of these measurements as well as the magnitude of changes that can be seen during LCD.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male or female subjects between the ages of 18 and 55 years, inclusive
  • Body Mass Index (BMI) 27-30 kg/m2, inclusive, with hypertension, controlled (<140 / <90) either by diet or medication.
  • BMI 30-40 kg/m2, inclusive.
  • An informed consent document signed and dated by the subject or a legally acceptable representative.
  • Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Exclusion Criteria:

  • Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, gastrointestinal, cardiovascular (hypertension controlled (<140 / <90) either by diet or medication is acceptable), hepatic, psychiatric, neurologic, allergic, (including drug allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing), muscle disease, diabetes, or severe uncontrolled hypertension.
  • Known hypersensitivity to phentermine, lidocaine, bupivicaine or any medication component of the study procedure.
  • Presence of cardiac pacemaker, implanted cardiac defibrillator, or brain aneurysm clips.
  • Any significant bleeding diathesis which could preclude recovery from the biopsy procedure. ASA, ibuprofen, and any other oral anti platelet agent will be discontinued at least 7 days prior to procedure.
  • Abnormal CK as per site laboratory ranges.
  • Subjects with either a medical history of or physical evidence of keloid scar formation upon physical examination.
  • 12-lead electrocardiogram (ECG) demonstrating a clinically significant abnormality.
  • Pregnant or nursing females or females less than 6 months postpartum from the scheduled date of collection.
  • Participation in non-routine rigorous exercise (e.g., road races, heavy lifting, etc.) within one week prior to the muscle biopsy procedures.
  • Presence of any condition in the investigator's opinion that may negatively affect subject safety or protocol adherence.
  • Females of childbearing potential (any female except those with tubal ligation, hysterectomy, or absence of menses > 2years) unwilling to use an approved method of contraception (condom, diaphragm, implantable uterine device (IUD) that does not release hormones).
  • Prior participation in the Magellan I study at the Translational Research Institute for Metabolism and Diabetes.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01616082

Locations
United States, Florida
Translational Research Institute for Metabolism and Diabetes
Orlando, Florida, United States, 32804
Sponsors and Collaborators
Translational Research Institute for Metabolism and Diabetes, Florida
Takeda
Investigators
Principal Investigator: Steven R Smith, MD Translational Research Institute for Metabolism and Diabetes
  More Information

Additional Information:
Publications:

Responsible Party: Translational Research Institute for Metabolism and Diabetes, Florida
ClinicalTrials.gov Identifier: NCT01616082     History of Changes
Other Study ID Numbers: TRIMDFH 266040, 266040
Study First Received: June 4, 2012
Last Updated: December 5, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Translational Research Institute for Metabolism and Diabetes, Florida:
fatty acid oxidation
Proton magnetic resonance spectroscopy

Additional relevant MeSH terms:
Metabolic Diseases
Overweight
Body Weight
Signs and Symptoms
Phentermine
Adrenergic Agents
Anti-Obesity Agents
Appetite Depressants
Autonomic Agents
Central Nervous System Agents
Central Nervous System Stimulants
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs
Sympathomimetics
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014