Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber

NCT ID: NCT05110274

Last Updated: 2023-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-08-26
• Study Completion Date: 2022-07-08

Brief Summary

This study is designed to test the reliability of a novel procedure for measuring metabolic flexibility, i.e., the ability to quickly adapt macronutrient oxidation to macronutrient availability, in a respiratory chamber. The investigators will compare paired measurements of metabolic flexibility determined 5-7 days apart in a metabolic chamber to assess reliability. The investigators will also compare their novel method of measuring metabolic flexibility in a respiratory chamber with a more convention method, metabolic flexibility during a hyperinsulinemic clamp.

Detailed Description

Metabolic flexibility (METFLEX) is the ability to adapt fuel oxidation to fuel availability and energy demands. Impaired METFLEX is associated with weight gain, ectopic lipid deposition, insulin resistance, and the potential development of type 2 diabetes. Even if impaired METFLEX shows promise as an early predictor of future metabolic dysfunction, longitudinal studies have been lacking because of the absence of simple methods for assessing METFLEX. This project will further validate (reproducibility and comparison with hyperinsulinemic-euglycemic clamps) a novel approach for measuring METFLEX recently developed by the PI.

METFLEX is commonly measured during a hyperinsulinemic-euglycemic clamp. Yet, this technique is questioned because it relies on a non-physiological stimulus (intravenous glucose and insulin) and inherently suppresses fat oxidation via non physiological hyperinsulinemic conditions. In contrast, impaired fat oxidation in response to a high-fat meal is a more physiological indicator of metabolic inflexibility. The investigators have recently developed a method for measuring METFLEX by assessing the dynamics in respiratory exchange ratio (RER) in response to a high-fat standardized dinner in a whole-body room indirect calorimeter. Securing extramural funding for the aforementioned longitudinal studies employing this novel methodology is presently limited due to a lack of the following preliminary data: 1) quantification of the intra-subject variability of this novel METFLEX measure to perform power calculations (sample size) in large-scale prospective clinical trials, and 2) comparison of our method to a more accepted measurement of METFLEX. The overarching goal of this method development project is to generate reproducibility and validity data of The investigators' new assessment of METFLEX in a whole-body room indirect calorimeter against the METFLEX measured by a hyperinsulinemic-euglycemic clamp.

Conditions

Metabolism

Study Design

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

Study Groups

Sequential measurements of metabolic flexibility

Study participants will undergo three assessments of metabolic flexibility. Two measurements of metabolic flexibility will be conducted during two separate overnight stay in a metabolic chamber approximately 5-7 days apart. The third measurement of metabolic flexibility will be assessed during a hyperinsulinemic-euglycemic clamp procedure conducted 7-28 days following the completion of the second overnight stay in the metabolic chamber.

Group Type: EXPERIMENTAL

Overnight Metabolic Flexibility

Intervention Type: PROCEDURE

Participants will spend 13 hours (overnight) in a metabolic chamber where they will be fed a single high-fat supper meal. Energy expenditure, respiratory exchange ratio (RER), and 12-h oxidation of CHO, fat, and protein will be calculated and used to determine metabolic flexibility, i.e. change in RER from baseline.

Clamp Metabolic Flexibility

Intervention Type: PROCEDURE

Metabolic flexibility with be assessed during a 2-step hyperinsulinemic-euglycemic clamp procedure. The clamp will be performed for four hours, two hours at an insulin dose of 10 mU/m\^2/min and two hours at an insulin dose of 80 mU/m\^2/min. Resting metabolic rate will be determined via hood indirect calorimetry at baseline, before insulin onset, and during the final 30 min of each step of the clamp. Metabolic flexibility will be determined by comparing the resting metabolic rate during baseline and during the final 30 min of each step of the clamp.

Interventions

Overnight Metabolic Flexibility

Participants will spend 13 hours (overnight) in a metabolic chamber where they will be fed a single high-fat supper meal. Energy expenditure, respiratory exchange ratio (RER), and 12-h oxidation of CHO, fat, and protein will be calculated and used to determine metabolic flexibility, i.e. change in RER from baseline.

Intervention Type: PROCEDURE

Clamp Metabolic Flexibility

Metabolic flexibility with be assessed during a 2-step hyperinsulinemic-euglycemic clamp procedure. The clamp will be performed for four hours, two hours at an insulin dose of 10 mU/m\^2/min and two hours at an insulin dose of 80 mU/m\^2/min. Resting metabolic rate will be determined via hood indirect calorimetry at baseline, before insulin onset, and during the final 30 min of each step of the clamp. Metabolic flexibility will be determined by comparing the resting metabolic rate during baseline and during the final 30 min of each step of the clamp.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• BMI between 18.5 kg/m^2 and 35 kg/m^2 (±0.5 kg/m^2 will be accepted)
• Willing to consume pre-prepared meals
• Non pregnant
• Bilateral oophorectomy or use of the following contraceptive methods (females only):

1. monophasic oral contraceptives

2. progesterone-only oral contraceptives

3. injectable or implantable progesterone-only contraceptives

Exclusion Criteria

• Unstable weight in the last 3 months [gain or loss >7 lb (or 3.2 kg)]
• Currently working shift work
• Smoking or use of tobacco products within the last 3 months
• History of clinically diagnosed diabetes or a fasting blood glucose >126 mg/dL
• Average screening blood pressure >140/90 mmHg
• Previous bariatric surgery (or other surgeries) for obesity or weight loss
• Use of medications affecting metabolism or sleep**
• History of cardiovascular disease, neurological disease, or other chronic diseases that affect sleep or metabolism
• Pregnant, planning to become pregnant, or breastfeeding
• Adherence to special restrained diets (e.g., low-carbohydrate, low-fat, or vegetarian/vegan diets) over the last 3 months.

• Sporadic use of these medications is acceptable (however, enrollment will be evaluated on a case-by-case basis). If taking sporadically, participants should not be taking the medication for 1-month prior to the first visit.

NOTE: Participants may also be excluded if deemed medically necessary by study Medical Investigator.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Pennington Biomedical Research Center

OTHER

Sponsor Role: lead

Responsible Party

David McDougal

Assistant Professor - Research

Responsibility Role: PRINCIPAL_INVESTIGATOR

Locations

Pennington Biomedical Research Center

Baton Rouge, Louisiana, United States

Countries

United States

Other Identifiers

PBRC 2021-031

Identifier Type: -

Identifier Source: org_study_id