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

Primary Purpose

Obesity, Insulin Resistance

Status
Completed
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.
Sponsored by
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Obesity

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5

Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) < 2.5

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Area under the curve of branched-chain amino acids.
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.

Secondary Outcome Measures

Area under the curve of branched-chain keto acids.
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.
Area under the curve of insulin.
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.
Area under the curve of glucose.
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.
Respiratory quotient.
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.
Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)
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.
Expression of the enzyme branched-chain keto acid dehydrogenase (BCKDH)
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.

Full Information

First Posted
May 7, 2021
Last Updated
July 29, 2022
Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
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1. Study Identification

Unique Protocol Identification Number
NCT04886973
Brief Title
Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.
Acronym
BCAA
Official Title
Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.
Study Type
Interventional

2. Study Status

Record Verification Date
July 2022
Overall Recruitment Status
Completed
Study Start Date
March 31, 2022 (Actual)
Primary Completion Date
July 29, 2022 (Actual)
Study Completion Date
July 29, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Obesity, Insulin Resistance

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The groups will receive the treatment simultaneously
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) ≥ 2.5
Arm Type
Experimental
Arm Description
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.
Arm Title
Subjects with a Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) < 2.5
Arm Type
Experimental
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
Administration of an 8% crystalline L-amino acid solution with high concentrations of branched chain amino acids.
Intervention Description
Intravenous administration of 8% crystalline L-amino acids with high concentrations of branched chain amino acids.
Primary Outcome Measure Information:
Title
Area under the curve of branched-chain amino acids.
Description
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.
Time Frame
2 hours
Secondary Outcome Measure Information:
Title
Area under the curve of branched-chain keto acids.
Description
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.
Time Frame
2 hours
Title
Area under the curve of insulin.
Description
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.
Time Frame
2 hours
Title
Area under the curve of glucose.
Description
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.
Time Frame
2 hours
Title
Respiratory quotient.
Description
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.
Time Frame
2 hours
Title
Expression of the enzyme branched-chain aminotransferase 2 (BCAT2)
Description
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.
Time Frame
2 hours
Title
Expression of the enzyme branched-chain keto acid dehydrogenase (BCKDH)
Description
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.
Time Frame
2 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
MARIA VIRIDIANA OLIN SANDOVAL, Dr
Organizational Affiliation
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran
Official's Role
Principal Investigator
Facility Information:
Facility Name
Instituto Nacional de Ciencias Medicas Y Nutricion Salvador Zubiran
City
Mexico
ZIP/Postal Code
14080
Country
Mexico

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
16424141
Citation
Shimomura Y, Yamamoto Y, Bajotto G, Sato J, Murakami T, Shimomura N, Kobayashi H, Mawatari K. Nutraceutical effects of branched-chain amino acids on skeletal muscle. J Nutr. 2006 Feb;136(2):529S-532S. doi: 10.1093/jn/136.2.529S.
Results Reference
background
PubMed Identifier
28127425
Citation
Zhang S, Zeng X, Ren M, Mao X, Qiao S. Novel metabolic and physiological functions of branched chain amino acids: a review. J Anim Sci Biotechnol. 2017 Jan 23;8:10. doi: 10.1186/s40104-016-0139-z. eCollection 2017.
Results Reference
background
PubMed Identifier
16365084
Citation
Brosnan JT, Brosnan ME. Branched-chain amino acids: enzyme and substrate regulation. J Nutr. 2006 Jan;136(1 Suppl):207S-11S. doi: 10.1093/jn/136.1.207S.
Results Reference
background
PubMed Identifier
19356713
Citation
Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, Haqq AM, Shah SH, Arlotto M, Slentz CA, Rochon J, Gallup D, Ilkayeva O, Wenner BR, Yancy WS Jr, Eisenson H, Musante G, Surwit RS, Millington DS, Butler MD, Svetkey LP. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 2009 Apr;9(4):311-26. doi: 10.1016/j.cmet.2009.02.002. Erratum In: Cell Metab. 2009 Jun;9(6):565-6.
Results Reference
background
PubMed Identifier
23043162
Citation
Floegel A, Stefan N, Yu Z, Muhlenbruch K, Drogan D, Joost HG, Fritsche A, Haring HU, Hrabe de Angelis M, Peters A, Roden M, Prehn C, Wang-Sattler R, Illig T, Schulze MB, Adamski J, Boeing H, Pischon T. Identification of serum metabolites associated with risk of type 2 diabetes using a targeted metabolomic approach. Diabetes. 2013 Feb;62(2):639-48. doi: 10.2337/db12-0495. Epub 2012 Oct 4.
Results Reference
background
PubMed Identifier
27642608
Citation
Zhao X, Han Q, Liu Y, Sun C, Gang X, Wang G. The Relationship between Branched-Chain Amino Acid Related Metabolomic Signature and Insulin Resistance: A Systematic Review. J Diabetes Res. 2016;2016:2794591. doi: 10.1155/2016/2794591. Epub 2016 Aug 25.
Results Reference
background
PubMed Identifier
21423183
Citation
Wang TJ, Larson MG, Vasan RS, Cheng S, Rhee EP, McCabe E, Lewis GD, Fox CS, Jacques PF, Fernandez C, O'Donnell CJ, Carr SA, Mootha VK, Florez JC, Souza A, Melander O, Clish CB, Gerszten RE. Metabolite profiles and the risk of developing diabetes. Nat Med. 2011 Apr;17(4):448-53. doi: 10.1038/nm.2307. Epub 2011 Mar 20.
Results Reference
background
PubMed Identifier
25287287
Citation
Lynch CJ, Adams SH. Branched-chain amino acids in metabolic signalling and insulin resistance. Nat Rev Endocrinol. 2014 Dec;10(12):723-36. doi: 10.1038/nrendo.2014.171. Epub 2014 Oct 7.
Results Reference
background
PubMed Identifier
25260659
Citation
Serralde-Zuniga AE, Guevara-Cruz M, Tovar AR, Herrera-Hernandez MF, Noriega LG, Granados O, Torres N. Omental adipose tissue gene expression, gene variants, branched-chain amino acids, and their relationship with metabolic syndrome and insulin resistance in humans. Genes Nutr. 2014 Nov;9(6):431. doi: 10.1007/s12263-014-0431-5. Epub 2014 Sep 27.
Results Reference
background
PubMed Identifier
23057765
Citation
Gunnerud U, Holst JJ, Ostman E, Bjorck I. The glycemic, insulinemic and plasma amino acid responses to equi-carbohydrate milk meals, a pilot- study of bovine and human milk. Nutr J. 2012 Oct 12;11:83. doi: 10.1186/1475-2891-11-83.
Results Reference
background

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Effect of Insulin Resistance on Branched Chain Amino Acid Metabolism.

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