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

NCT05110274 | Completed

• 1 other identifier: PBRC 2021-031
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Metabolism

Outcome Measures

Primary Outcomes (2)

• peak decrease in overnight respiratory exchange ratio

  mean of peak decrease in respiratory exchange ratio (baseline values -nadir values) following the test meal during an overnight stay in a respiratory chamber. Peak values are defined as the lowest respiratory exchange ratio value measured during the sleep period, 11pm-5am Baseline values are measured 1h prior to meal (5:00-5:45pm) An increase in this value indicates increased metabolic flexibility.

  12 hours

• change in respiratory exchange ratio during high-dose insulin infusion

  mean of peak increase in respiratory exchange ratio during a 80 mU/m\^2/min insulin infusion (insulin stimulated - baseline values) that is conducted during an hyperinsulinemic-euglycemic clamp procedure.. Insulin-stimulated values are defined as the mean respiratory exchange ratio value measured during the final 30 min of a 2 hour 80 mU/m\^2/min insulin infusion. Baseline values are measured 30 min prior to the start of the hyperinsulinemic-euglycemic clamp procedure. An increase in this value indicates increased metabolic flexibility.

  4.5 hours

Secondary Outcomes (5)

• slope of respiratory exchange ratio

  12 hours

• respiratory exchange ratio/food quotient (RER:FQ ratio)

  12 hours

• change in respiratory exchange ratio during low-dose insulin infusion

  4.5 hours

• Time to nadir respiratory exchange ratio

  12 hours

• Time to food quotient

  12 hours

Study Arms (1)

Sequential measurements of metabolic flexibility

EXPERIMENTAL

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.

Procedure: Overnight Metabolic Flexibility; Procedure: Clamp Metabolic Flexibility

Interventions

Overnight Metabolic Flexibility 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.

Sequential measurements of metabolic flexibility

Clamp Metabolic Flexibility 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.

Sequential measurements of metabolic flexibility

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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):
• monophasic oral contraceptives
• progesterone-only oral contraceptives
• injectable or implantable progesterone-only contraceptives

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pennington Biomedical Research Center: lead

Study Sites (1)

Pennington Biomedical Research Center

Baton Rouge, Louisiana, 70808-4124, United States

Location

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor - Research

Study Record Dates

• First Submitted: October 4, 2021
• First Posted: November 5, 2021
• Study Start: August 26, 2021
• Primary Completion: July 8, 2022
• Study Completion: July 8, 2022
• Last Updated: March 9, 2023

Record last verified: 2023-03

Locations

US (1)