NCT07329088

Brief Summary

The primary purpose of this study is to determine whether isoleucine repletion attenuates increases in insulin sensitivity typically observed when people with obesity follow a healthy, low-isoleucine diet.

Trial Health

50
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Timeline
33mo left

Started May 2026

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 7, 2026

Completed
2 days until next milestone

First Posted

Study publicly available on registry

January 9, 2026

Completed
4 months until next milestone

Study Start

First participant enrolled

May 4, 2026

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 31, 2029

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

January 31, 2029

Last Updated

April 15, 2026

Status Verified

January 1, 2026

Enrollment Period

2.7 years

First QC Date

January 7, 2026

Last Update Submit

April 10, 2026

Conditions

Prediabetes (Insulin Resistance, Impaired Glucose Tolerance)Metabolic Syndrome (MetS)Obesity & Overweight

Keywords

L-IsoleucineInsulin ResistanceHyperglycemiaMuscle, SkeletalAmino AcidsPrediabetic StateDietMechanistic Target of Rapamycin Complex 1Adipose TissueBody Composition

Outcome Measures

Primary Outcomes (1)

  • Change in insulin sensitivity (M value)

    The primary clinical outcome is insulin sensitivity, quantified as the M value derived from the hyperinsulinemic-euglycemic clamp. Hyperinsulinemic-euglycemic clamps will be performed to measure insulin sensitivity (IS). Briefly, after a ≥8 hour fast, participants will be admitted to the PC clinical unit and two IVs will be inserted; one for infusion, the other for blood draws. The primary metric will be an absolute change in M value from baseline to post intervention.

    The first measure is taken immediately after the run-in and the final measure will be taken immediately after the completion of the low-isoleucine diet and isoleucine vs placebo supplement intervention four weeks later.

Secondary Outcomes (3)

  • Change in ratio of phosphorylation IRS-1 in skeletal muscle

    The first measure is taken immediately after the run-in and the final measure will be taken immediately after the completion of the low-isoleucine diet and isoleucine vs placebo supplement intervention four weeks later.

  • Absolute change in visceral fat

    The first measure is taken immediately after the run-in and the final measure will be taken immediately after the completion of the low-isoleucine diet and isoleucine vs placebo supplement intervention four weeks later.

  • Change in ratio of phosphorylation Akt in skeletal muscle

    The first measure is taken immediately after the run-in and the final measure will be taken immediately after the completion of the low-isoleucine diet and isoleucine vs placebo supplement intervention four weeks later.

Study Arms (2)

Isoleucine group

EXPERIMENTAL

Participants will be randomized to receive low-isoleucine diet and isoleucine supplement

Dietary Supplement: L-IsoleucineOther: Low-isoleucine diet

Placebo group

ACTIVE COMPARATOR

Participants will be randomized to receive low-isoleucine diet and placebo supplement

Other: Low-isoleucine diet

Interventions

L-IsoleucineDIETARY_SUPPLEMENT

Participants will follow a habitual American style diet. All participants transition to a healthy, low-isoleucine diet the study team provides, but only the isoleucine group receives isoleucine supplements to replete the overall diet to typical intake levels.

Isoleucine group
Low-isoleucine dietOTHER

Healthy, weight-maintaining, low-isoleucine meals and snacks will be provided directly to participants for 4 weeks. Diets are formulated by registered dietitians to meet energy, protein, and amino-acid requirements while minimizing weight change; target macronutrient distribution ≈ 10% protein / 60% carbohydrate / 30% fat38. Isoleucine content will meet minimum needs of 23 mg/kg.

Isoleucine groupPlacebo group

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • BMI ≥ 30
  • Meeting at least three metabolic syndrome criteria
  • Follow an American style diet

You may not qualify if:

  • Type 1 or 2 Diabetes diagnosis
  • Medical condition or medication that affects insulin sensitivity, weight, or metabolism
  • More than 5% weight change in 3 previous months
  • Restrictive dietary pattern
  • History of bariatric surgery
  • Food allergy more severe than grade 1 on the CoFAR Grading Scale for Systemic Allergic Reactions, Version 3.0
  • Allergy to lidocaine.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Kentucky

Lexington, Kentucky, 40536, United States

Location

Related Publications (9)

  • Doi M, Yamaoka I, Fukunaga T, Nakayama M. Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. Biochem Biophys Res Commun. 2003 Dec 26;312(4):1111-7. doi: 10.1016/j.bbrc.2003.11.039.

    PMID: 14651987BACKGROUND

  • Zhang S, Yang Q, Ren M, Qiao S, He P, Li D, Zeng X. Effects of isoleucine on glucose uptake through the enhancement of muscular membrane concentrations of GLUT1 and GLUT4 and intestinal membrane concentrations of Na+/glucose co-transporter 1 (SGLT-1) and GLUT2. Br J Nutr. 2016 Aug;116(4):593-602. doi: 10.1017/S0007114516002439.

    PMID: 27464458BACKGROUND

  • Woo SL, Yang J, Hsu M, Yang A, Zhang L, Lee RP, Gilbuena I, Thames G, Huang J, Rasmussen A, Carpenter CL, Henning SM, Heber D, Wang Y, Li Z. Effects of branched-chain amino acids on glucose metabolism in obese, prediabetic men and women: a randomized, crossover study. Am J Clin Nutr. 2019 Jun 1;109(6):1569-1577. doi: 10.1093/ajcn/nqz024.

    PMID: 31005973BACKGROUND

  • Drummond MJ, Bell JA, Fujita S, Dreyer HC, Glynn EL, Volpi E, Rasmussen BB. Amino acids are necessary for the insulin-induced activation of mTOR/S6K1 signaling and protein synthesis in healthy and insulin resistant human skeletal muscle. Clin Nutr. 2008 Jun;27(3):447-56. doi: 10.1016/j.clnu.2008.01.012. Epub 2008 Mar 14.

    PMID: 18342407BACKGROUND

  • Yu D, Richardson NE, Green CL, Spicer AB, Murphy ME, Flores V, Jang C, Kasza I, Nikodemova M, Wakai MH, Tomasiewicz JL, Yang SE, Miller BR, Pak HH, Brinkman JA, Rojas JM, Quinn WJ 3rd, Cheng EP, Konon EN, Haider LR, Finke M, Sonsalla M, Alexander CM, Rabinowitz JD, Baur JA, Malecki KC, Lamming DW. The adverse metabolic effects of branched-chain amino acids are mediated by isoleucine and valine. Cell Metab. 2021 May 4;33(5):905-922.e6. doi: 10.1016/j.cmet.2021.03.025. Epub 2021 Apr 21.

    PMID: 33887198BACKGROUND

  • Yeh CY, Chini LCS, Davidson JW, Garcia GG, Gallagher MS, Freichels IT, Calubag MF, Rodgers AC, Green CL, Babygirija R, Sonsalla MM, Pak HH, Trautman M, Hacker TA, Miller RA, Simcox J, Lamming DW. Late-life isoleucine restriction promotes physiological and molecular signatures of healthy aging. bioRxiv [Preprint]. 2024 Jan 9:2023.02.06.527311. doi: 10.1101/2023.02.06.527311.

    PMID: 36798157BACKGROUND

  • Trautman ME, Richardson NE, Lamming DW. Protein restriction and branched-chain amino acid restriction promote geroprotective shifts in metabolism. Aging Cell. 2022 Jun;21(6):e13626. doi: 10.1111/acel.13626. Epub 2022 May 8.

    PMID: 35526271BACKGROUND

  • Green CL, Trautman ME, Chaiyakul K, Jain R, Alam YH, Babygirija R, Pak HH, Sonsalla MM, Calubag MF, Yeh CY, Bleicher A, Novak G, Liu TT, Newman S, Ricke WA, Matkowskyj KA, Ong IM, Jang C, Simcox J, Lamming DW. Dietary restriction of isoleucine increases healthspan and lifespan of genetically heterogeneous mice. Cell Metab. 2023 Nov 7;35(11):1976-1995.e6. doi: 10.1016/j.cmet.2023.10.005.

    PMID: 37939658BACKGROUND

  • Fontana L, Cummings NE, Arriola Apelo SI, Neuman JC, Kasza I, Schmidt BA, Cava E, Spelta F, Tosti V, Syed FA, Baar EL, Veronese N, Cottrell SE, Fenske RJ, Bertozzi B, Brar HK, Pietka T, Bullock AD, Figenshau RS, Andriole GL, Merrins MJ, Alexander CM, Kimple ME, Lamming DW. Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health. Cell Rep. 2016 Jul 12;16(2):520-530. doi: 10.1016/j.celrep.2016.05.092. Epub 2016 Jun 23.

    PMID: 27346343BACKGROUND

MeSH Terms

Conditions

Prediabetic StateInsulin ResistanceGlucose IntoleranceMetabolic SyndromeObesityOverweightHyperglycemia

Interventions

Isoleucine

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System DiseasesHyperinsulinismOvernutritionNutrition DisordersBody WeightSigns and SymptomsPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Amino Acids, Branched-ChainAmino AcidsAmino Acids, Peptides, and ProteinsAmino Acids, Essential

Study Officials

  • Jean Fry, PhD

    University of Kentucky

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
TRIPLE
Who Masked
PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR INVESTIGATOR
PI Title
Associate Professor-PI

Study Record Dates

First Submitted

January 7, 2026

First Posted

January 9, 2026

Study Start

May 4, 2026

Primary Completion (Estimated)

January 31, 2029

Study Completion (Estimated)

January 31, 2029

Last Updated

April 15, 2026

Record last verified: 2026-01

Data Sharing

IPD Sharing
Will not share

Locations

US(1)