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

AdventHealth Translational Research Institute

Status: Completed

Conditions: Metabolic Diseases; Overweight; Obesity

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

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01616082

TRIMDFH 266040

266040 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 39 patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No 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.

Trial design

Primary purpose: Basic Science

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

39 participants in 2 patient groups

Overwight/Obese with no drug

Active Comparator group

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.

Treatment:

Behavioral: Low Calorie Diet (LCD)

Overweight/obese with Phentermine

Active Comparator group

Description:

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.

Treatment:

Behavioral: Low Calorie Diet (LCD)

Drug: Phentermine