Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism. (BCAA)

July 29, 2022 updated by: Maria Viridiana Olin Sandoval, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
It has been observed that subjects with obesity and insulin resistance have higher concentrations of branched chain amino acids in plasma or serum. However, this association has been established under fasting conditions, so they only give information about a metabolic state and do not reflect the dynamics and flexibility of the metabolism of these amino acids in the absence or presence of insulin resistance. The main aim of this study is to compare the catabolism of branched chain amino acids and their keto acids in subjects with and without insulin resistance, after the infusion of an amino acid solution with high concentration of the branched chain amino acids, leucine, valine, and isoleucine. The results of this project will allow the investigators to understand the dynamics of the branched chain amino acids and their derivatives, and its relationship with insulin resistance, which could eventually be used to design nutritional strategies to treat insulin resistance and thus, delay the development of type 2 diabetes.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

An 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids, leucine, isoleucine, and valine, will be administered intravenously. The dose will be calculated considering the 25% of the estimated protein per day. For example, if the patient is 70 kg and the investigators consider 1g/kg/day, the amount of protein to be administered will be 17.5 grams (70 x 0.25 = 17.5 grams). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician. After the administration of the L- amino acid solution, the investigators will take blood samples at 0, 15, 30, 45, 60, 90 and 120 minutes to determine the area under the curve for glucose, insulin, amino acids and branched chain keto acids.

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Mexico
      • Mexico, Mexico, 14080
        • Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 50 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Inclusion criteria for cases (subjects with insulin resistance).

  • Male and female.
  • Adults between 18 and 50 years of age.
  • Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m2.
  • HOMA index ≥ 2.5
  • In the case of women, being in the follicular phase of the menstrual cycle.

Inclusion criteria for controls (subjects without insulin resistance).

  • Male and female
  • Adults between 18 and 50 years of age.
  • Body Mass Index (BMI) ≥ 18.5 and ≤ 40 kg/m2.
  • HOMA index < 2.5
  • Blood glucose < 100 mg/dL
  • In the case of women, being in the follicular phase of the menstrual cycle.

Exclusion Criteria:

  • Patients with any type of diabetes.
  • Patients with kidney disease diagnosed by any physician.
  • Patients with creatinine > 1.3 mg/dL for men and > 1.1 mg/dL for women and/or Blood Urea Nitrogen (BUN) > 20 mg/dL.
  • Patients with acquired diseases secondarily producing obesity and diabetes.
  • Patients who have suffered a cardiovascular event.
  • Weight loss > 3 kg in the last 3 months.
  • Patients with any catabolic diseases.
  • Pregnancy status.
  • Positive smoking.
  • Treatment with any medication (except contraceptives and proton pump inhibitors)
  • Having suffered any infection in the last 20 days.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5
Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids. The dose will be calculated considering the 25% of the estimated protein per day (1 g/kg/day). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician.
Other: Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.
Intravenous administration of 8% crystalline L-amino acids with high concentrations of branched chain amino acids.
Experimental: Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) < 2.5
Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids. The dose will be calculated considering the 25% of the estimated protein per day (1 g/kg/day). This dose will be placed in a short peripheral intravenous catheter and administered at a rate of 1.5ml per minute, using an infusion pump. The patient will be monitored all the time by a physician.
Other: Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.
Intravenous administration of 8% crystalline L-amino acids with high concentrations of branched chain amino acids.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the curve of branched-chain amino acids.
Time Frame: 2 hours

Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The branched chain amino acids concentration will be determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS), and the area under the curve will be calculated using the trapezoidal rule.
2 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Area under the curve of branched-chain keto acids.
Time Frame: 2 hours

Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The branched chain keto acids concentration will be determined by liquid chromatography coupled to mass spectrometry (LC-MS/MS), and the area under the curve will be calculated using the trapezoidal rule.
2 hours
Area under the curve of insulin.
Time Frame: 2 hours

Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The insulin concentration will be determined using an ELISA assay and the area under the curve will be calculated using the trapezoidal rule.
2 hours
Area under the curve of glucose.
Time Frame: 2 hours

Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The glucose concentration will be determined using an enzymatic assay (Hexokinase) and the area under the curve will be calculated using the trapezoidal rule.
2 hours
Respiratory quotient.
Time Frame: 2 hours
Time Frame: Measured for 0,15,30,45,60,90,120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids The respiratory quotient will be determined by indirect calorimetry and the area under the curve will be calculated using the trapezoidal rule.
2 hours
Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)
Time Frame: 2 hours

Time Frame: Measured for 0, 60 and 120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The expression of enzyme branched chain aminotransferase 2 (BCAT2) will be determined in mononuclear cells isolated from blood by Western Blot and quantitative PCR.
2 hours
Expression of the enzyme branched-chain keto acid dehydrogenase (BCKDH)
Time Frame: 2 hours

Time Frame: Measured for 0, 60 and 120 minutes following the intravenous administration of the amino acid solution rich in branched chain amino acids.

The expression of enzyme branched chain ketoacid dehydrogenase (BCKDH) will be determined in mononuclear cells isolated from blood by Western Blot and quantitative PCR.
2 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Investigators

  • Principal Investigator: MARIA VIRIDIANA OLIN SANDOVAL, Dr, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 31, 2022

Primary Completion (Actual)

July 29, 2022

Study Completion (Actual)

July 29, 2022

Study Registration Dates

First Submitted

May 7, 2021

First Submitted That Met QC Criteria

May 7, 2021

First Posted (Actual)

May 14, 2021

Study Record Updates

Last Update Posted (Actual)

August 2, 2022

Last Update Submitted That Met QC Criteria

July 29, 2022

Last Verified

July 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FNU-3549-20-23-1

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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