Protection Against Insulin Resistance in Obesity

NCT ID: NCT02717832

Last Updated: 2022-05-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-03-31
• Study Completion Date: 2019-08-09

Brief Summary

The overall goal of this project is to identify factors that "protect" some obese adults from becoming insulin resistant. Identifying mechanisms that help protect some obese adults from developing insulin resistance could lead to novel, targeted therapeutic and/or preventative strategies for obese adults who are insulin resistant.

Detailed Description

SCREENING PROCEDURES Participants will undergo a battery of initial screening tests including: a detailed health history and physical examination, a physical activity questionnaire, and a body composition assessment. All women will undergo a urine pregnancy test.

GENERAL STUDY DESIGN To avoid potential confounding hormonal effects, all women will be studied in the early follicular phase of their menstrual cycle. Subjects will be advised of what they should be eating in the 3 days leading up to their hospital visit to maintain their weight. Subjects will also complete a three day food journal before their hospital visit. The day prior to the study trial admission, subjects will need to eat pre-prepared standardized meals for breakfast, lunch, dinner and an evening snack that the study team has given them.

Subjects will be admitted to the Michigan Clinical Research Unit (MCRU) in the morning after a 12-hour, overnight fast. After arrival, subjects will rest quietly in their room for about 30 minutes. The study team will then measure subjects resting metabolic rate for about 20 minutes. After this test, an intravenous (IV) catheter will be placed for infusions and a second IV will be placed in vein of the opposite arm for blood sampling.

After the IV placement, the study team will begin a tracer-labeled glucose, or "sugar," infusion. The study team will then remove a small sample of muscle from the subjects thigh. This muscle biopsy procedure involves numbing a nickel-sized portion of the skin of the thigh with a local anesthetic, making a small incision (1/4 inch), and removing a small piece of muscle (approximately the size of 2-3 grains of rice). The incision will then be closed with a piece of sterile tape. The study team will also obtain a small sample of fat tissue from the area just underneath the skin near the belly button. This procedure involves numbing a small region of skin near the belly button with a local anesthetic, using a needle a small amount of fat tissue is removed from underneath the skin. During the procedure subjects will feel some pinching and pulling, but it should not be very painful. The injury resulting from the muscle and fat tissue biopsies is rather minor. Subjects will likely have some bruising and mild soreness, but it should not prevent them from performing their general daily activities.

Approximately 2.5 hours after admission, the study team will begin the tracer-labeled fat infusion. The tracer-labeled fats the study team are infusing occur naturally in the body. By injecting a slightly greater amount of this substance than what is already in the body the study team will be able to measure the rate of fat breakdown and fat burning. After about 50 minutes of the infusion, three blood samples will be obtained in 5 min intervals.

After, the study team will begin a hyperinsulinemic-euglycemic clamp procedure (a procedure to measure the body's sensitivity to insulin). During this procedure the study team will infuse insulin and glucose through the IV and will collect blood samples every 5 minutes for the duration of the procedure to monitor the subjects blood glucose and blood insulin concentrations. This procedure is designed to last 2 hours. The study team will change the infusion rate of glucose accordingly to ensure that the subjects blood sugar is maintained at a healthy/normal level. The study team will also infuse a small amount of potassium to make sure potassium concentrations remain at healthy/normal levels. About 30 minutes after starting this procedure to measure the body's sensitivity to insulin, the study team will collect another sample of muscle from the thigh and fat tissue from the area just underneath the skin near the belly button. After completing the hyperinsulinemic-euglycemic clamp procedure, subjects will be provided a meal, and the study team will continue to monitor the subjects blood glucose concentration until stable.

When the subjects vital signs are stable, the study team will also measure percent body fat using a Dual Energy X-ray Absorptiometry (DEXA) and intra-abdominal fat by Magnetic resonance imaging (MRI). When the DEXA scan and MRI tests have been completed, subjects will be discharged from the hospital. Depending on scheduling, however, the DEXA scan and MRI tests may be performed on a separate occasion from the study trial admission.

Conditions

Obesity; Insulin Resistance

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Insulin Sensitivity

Group Type: EXPERIMENTAL

hyperinsulinemic-euglycemic clamp

Intervention Type: DRUG

Interventions

hyperinsulinemic-euglycemic clamp

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Body mass index [BMI]: 30-40 kg/m2
• Age: 18-45 years
• All women must be pre-menopausal
• Non-exerciser: no regularly planned exercise/physical activity

Exclusion Criteria

• Weight instability ≥ ±3kg ≥ 6 months
• Medications known to affect lipid and/or glucose metabolism
• Pregnancy or actively breast feeding

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

University of Michigan

OTHER

Sponsor Role: lead

Responsible Party

Jeffrey F Horowitz

Professor, Movement Science and Director, Substrate Metabolism Laboratory

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jeffrey F Horowitz

Role: PRINCIPAL_INVESTIGATOR

University of Michigan

Locations

University of Michigan

Ann Arbor, Michigan, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

HUM00111275

Identifier Type: -

Identifier Source: org_study_id