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

NCT01616082 | Completed Results DMC

• 2 other identifiers: TRIMDFH 266040266040
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity; Overweight; Metabolic Diseases

Keywords

fatty acid oxidation; Proton magnetic resonance spectroscopy

Outcome Measures

Primary Outcomes (2)

• 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)

  Days 0, 14

• 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)

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

Secondary Outcomes (1)

• Soleus IMCL Content

  Days -7, -1, 14, 56

Study Arms (2)

Overwight/Obese with no drug

ACTIVE COMPARATOR

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.

Behavioral: Low Calorie Diet (LCD)

Overweight/obese with Phentermine

ACTIVE COMPARATOR

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.

Behavioral: Low Calorie Diet (LCD); Drug: Phentermine

Interventions

Low Calorie Diet (LCD) BEHAVIORAL

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.

Overweight/obese with Phentermine; Overwight/Obese with no drug

Phentermine DRUG

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.

Overweight/obese with Phentermine

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• AdventHealth Translational Research Institute: lead
• Takeda: collaborator

Study Sites (1)

Translational Research Institute for Metabolism and Diabetes

Orlando, Florida, 32804, United States

Location

Related Publications (19)

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• Tamura Y, Tanaka Y, Sato F, Choi JB, Watada H, Niwa M, Kinoshita J, Ooka A, Kumashiro N, Igarashi Y, Kyogoku S, Maehara T, Kawasumi M, Hirose T, Kawamori R. Effects of diet and exercise on muscle and liver intracellular lipid contents and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab. 2005 Jun;90(6):3191-6. doi: 10.1210/jc.2004-1959. Epub 2005 Mar 15.

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• Whytock KL, Corbin KD, Parsons SA, Pachori A, Bock CP, Jones KP, Smith JS, Yi F, Xie H, Petucci CJ, Gardell SJ, Smith SR. Metabolic adaptation characterizes short-term resistance to weight loss induced by a low-calorie diet in overweight/obese individuals. Am J Clin Nutr. 2021 Jul 1;114(1):267-280. doi: 10.1093/ajcn/nqab027.

  PMID: 33826697 DERIVED

Related Links

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

MeSH Terms

Conditions

Obesity; Overweight; Metabolic Diseases

Interventions

Caloric Restriction; Phentermine

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet Therapy; Nutrition Therapy; Therapeutics; Energy Intake; Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena; Amphetamines; Phenethylamines; Ethylamines; Amines; Organic Chemicals

Results Point of Contact

• Title: Dr. Steven R. Smith
• Organization: Translational Research Institute for Metabolism and Diabetes

steven.r.smith.md@flhosp.org

407-303-7115

Study Officials

• Steven R Smith, MD

  Translational Research Institute for Metabolism and Diabetes

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2012
• First Posted: June 11, 2012
• Study Start: September 1, 2011
• Primary Completion: November 1, 2012
• Study Completion: November 1, 2012
• Last Updated: November 13, 2020
• Results First Posted: November 13, 2020

Record last verified: 2020-10

Locations

US (1)