MetabolismMETFLEX IINCT05110274
Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber
A study testing Overnight Metabolic Flexibility and Clamp Metabolic Flexibility in people with Metabolism, run by Pennington Biomedical Research Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Metabolism
- What is being tested?
- Overnight Metabolic Flexibility and Clamp Metabolic Flexibility
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Aug 2021to 8 Jul 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Pennington Biomedical Research Center
Baton Rouge, Louisiana, 70808-4124
About this study
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.
Read the 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
- Being tested
- Overnight Metabolic Flexibility, Clamp Metabolic Flexibility
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Overnight Metabolic FlexibilityProcedure or surgery
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 FlexibilityProcedure or surgery
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Procedure: Overnight Metabolic Flexibility; Procedure: Clamp Metabolic Flexibility |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 4.5 hours
Secondary outcomes (5)
slope of respiratory exchange ratio
This value indicates the speed and magnitude of the participants change in respiratory exchange ratio between the peak and nadir values measured overnight in the respiratory chamber.
A more negative value in this measurement indicates either a short time interval between the highest and lowest respiratory exchange ratio values measured and/or a large difference between the highest and lowest values of respiratory exchange ratio values measured.
Measured: 12 hours
respiratory exchange ratio/food quotient (RER:FQ ratio)
The ratio of the 12-h respiratory exchange ratio to the food quotient of the meal.
This measurement assesses the degree to which a participant's actual respiratory exchange ratio matches the theoretical respiratory exchange ratio that would be obtained if all the macronutrients in the test meal were oxidized during an overnight stay in a respiratory chamber.
A value of 1 indicates perfect agreement between measured and theoretical values. A value greater than 1 indicates a lack of fat oxidation, while a value less than 1 indicates a lack of carbohydrate oxidation.
Individuals with high metabolic flexibility should achieve values closer to 1 than individuals with low metabolic flexibility.
Measured: 12 hours
change in respiratory exchange ratio during low-dose insulin infusion
mean of peak increase in respiratory exchange ratio during a 10 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 10 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.
Measured: 4.5 hours
Time to nadir respiratory exchange ratio
Average time from meal to nadir respiratory exchange ratio value
This measurement indicates how long on average it took form the onset of the meal, 6pm, for the participants to achieve their lowest/nadir respiratory exchange ratio value during an overnight stay in a respiratory chamber..
Measured: 12 hours
Time to food quotient
Average time from meal to a participant's respiratory exchange ratio reaching the food quotient of the test meal
This measurement indicates how long on average it takes form the onset of the meal, 6pm, for the participants to register a respiratory exchange ratio equal to the food quotient of the test meal during an overnight stay in a respiratory chamber.
A reduction in this value indicates increased metabolic flexibility.
Measured: 12 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Nov 2021
- Study start26 Aug 2021
- Primary completion8 Jul 2022
- Study completion8 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MetabolismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pennington Biomedical Research Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, David McDougal, Pennington Biomedical Research Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05110274
- Sponsor's protocol ID
- PBRC 2021-031
- Acronym
- METFLEX II
- Status last verified
- Mar 2023
- First submitted
- 4 Oct 2021
- Last updated
- 9 Mar 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 Mar 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Validating a Novel Approach to Assess Metabolic Flexibility in a Respiratory Chamber
- ClinicalTrials.gov ID
- NCT05110274
- Acronym / sponsor ID
- METFLEX II / PBRC 2021-031
- Conditions
- Metabolism
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Pennington Biomedical Research CenterUniversity, hospital or other
- Study start
- 26 Aug 2021 (actual)
- Primary completion
- 8 Jul 2022 (actual)
- Study completion
- 8 Jul 2022 (actual)
- First posted
- 5 Nov 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Sequential measurements of metabolic flexibility | Experimental | Procedure: Overnight Metabolic Flexibility, Procedure: Clamp Metabolic FlexibilityStudy 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. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- 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):
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Overnight Metabolic FlexibilityParticipants 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. | Procedure or surgery | Sequential measurements of metabolic flexibility |
| Clamp Metabolic FlexibilityMetabolic 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. | Procedure or surgery | Sequential measurements of metabolic flexibility |
Primary outcome
peak decrease in overnight respiratory exchange ratio
Time frame: 12 hours
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.
change in respiratory exchange ratio during high-dose insulin infusion
Time frame: 4.5 hours
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.
5 secondary outcomes
slope of respiratory exchange ratio
Time frame: 12 hours
respiratory exchange ratio/food quotient (RER:FQ ratio)
Time frame: 12 hours
change in respiratory exchange ratio during low-dose insulin infusion
Time frame: 4.5 hours
Time to nadir respiratory exchange ratio
Time frame: 12 hours
Time to food quotient
Time frame: 12 hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Mar 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Overnight Metabolic Flexibility and Clamp Metabolic Flexibility in people with Metabolism, run by Pennington Biomedical Research Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Mar 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
peak decrease in overnight respiratory exchange ratio (time frame: 12 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Mar 2023.