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

Primary Purpose

Obesity, Overweight, Metabolic Diseases

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Low Calorie Diet (LCD)

Phentermine

About this trial

This is an interventional basic science trial for Obesity focused on measuring fatty acid oxidation, Proton magnetic resonance spectroscopy

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Translational Research Institute for Metabolism and Diabetes

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Arm Label

Overwight/Obese with no drug

Overweight/obese with Phentermine

Arm Description

After screening, overweight/obese subjects (BMI >27 - ≤40.0) subjects will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved.

After screening, overweight/obese (BMI >27.0 - ≤40.0) 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.

Outcomes

Primary Outcome Measures

Change From Baseline Amount of Fat Oxidation at 14 Days

Measured with respiratory quotient obtained with indirect calorimetry 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)

Fat Oxidation Rates at 1 Week Intervals

Measured with respiratory quotient using indirect calorimetry 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

Soleus IMCL Content

Measured with magnetic resonance spectroscopy (MRS) Expected results 1H-MRS can measure skeletal muscle (intramyocellular lipid) IMCL content with low test-retest variability 1H-MRS can sensitively monitor reductions (or lack thereof) in skeletal muscle IMCL during caloric restriction Reductions in IMCL will be higher in subjects with lower fasting respiratory quotients (RQ) at baseline/during LCD

Full Information

NCT ID

NCT01616082

First Posted

June 4, 2012

Last Updated

October 21, 2020

Sponsor

AdventHealth Translational Research Institute

Collaborators

Takeda

1. Study Identification

Unique Protocol Identification Number

NCT01616082

Brief Title

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

Acronym

MagellanII

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2020

Overall Recruitment Status

Completed

Study Start Date

September 2011 (undefined)

Primary Completion Date

November 2012 (Actual)

Study Completion Date

November 2012 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

AdventHealth Translational Research Institute

Collaborators

Takeda

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Obesity, Overweight, Metabolic Diseases

Keywords

fatty acid oxidation, Proton magnetic resonance spectroscopy

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

39 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Overwight/Obese with no drug

Arm Type

Active Comparator

Arm Description

After screening, overweight/obese subjects (BMI >27 - ≤40.0) subjects will be started on a low calorie diet (approximately 900-1000 kcal/d) until a target weight loss is achieved.

Arm Title

Overweight/obese with Phentermine

Arm Type

Active Comparator

Arm Description

Intervention Type

Behavioral

Intervention Name(s)

Low Calorie Diet (LCD)

Intervention Description

A Diet History Questionnaire was completed and subjects had dietary counseling and were provided shakes. The low calorie diet began, to continued for a period of 8 weeks.

Intervention Type

Drug

Intervention Name(s)

Phentermine

Intervention Description

Individuals not on track to achieve their target weight by four weeks received 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 were 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.

Primary Outcome Measure Information:

Title

Change From Baseline Amount of Fat Oxidation at 14 Days

Description

Time Frame

Days 0, 14

Title

Fat Oxidation Rates at 1 Week Intervals

Description

Time Frame

Days 0, 7, 14, 28, 49, 56

Secondary Outcome Measure Information:

Title

Soleus IMCL Content

Description

Time Frame

Days -7, -1, 14, 56

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven R Smith, MD

Organizational Affiliation

Translational Research Institute for Metabolism and Diabetes

Official's Role

Principal Investigator

Facility Information:

Facility Name

Translational Research Institute for Metabolism and Diabetes

City

Orlando

State/Province

Florida

ZIP/Postal Code

32804

Country

United States

12. IPD Sharing Statement

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Links:

URL

http://www.tri-md.org

Description

Translational Research Institute for Metabolism and Diabetes web page for more information on the study

Learn more about this trial

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

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