Isoleucine Addition Treatment Effects in a Controlled Diet Study (ISOLATE)

April 10, 2026 updated by: Jean L. Fry

ISOLeucine Addition Treatment Effects (ISOLATE) in a Controlled Diet Study

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Isoleucine restriction promotes insulin sensitivity in preclinical models and is a promising strategy for preventing type 2 diabetes. This project aims to identify clinical and molecular changes in skeletal muscle and adipose tissues when adults with obesity switch from a typical American style diet to a plant-based diet low in isoleucine with or without isoleucine repletion.

Study Type

Interventional

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

  • United States
    • Kentucky
      • Lexington, Kentucky, United States, 40536
        • University of Kentucky

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

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • 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.

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: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Isoleucine group
Participants will be randomized to receive low-isoleucine diet and isoleucine supplement
Dietary supplement: L-Isoleucine
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.
Other: Low-isoleucine diet
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.
Active Comparator: Placebo group
Participants will be randomized to receive low-isoleucine diet and placebo supplement
Other: Low-isoleucine diet
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in insulin sensitivity (M value)
Time Frame: 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.
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in ratio of phosphorylation IRS-1 in skeletal muscle
Time Frame: 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.
Phosphorylation of IRS-1 at Ser636/639 will be quantified in skeletal muscle tissue obtained at baseline and after the intervention. Levels of phosphorylated IRS-1 and total IRS-1 will be measured, and the outcome will be expressed as the change in the phospho-to-total IRS-1 protein ratio 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.
Absolute change in visceral fat
Time Frame: 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.
Abdominal adiposity will be assessed by computed tomography (CT). A single slice at the L4/L5level will be obtained at baseline and post-intervention. Visceral and subcutaneous fat volumes will be quantified using ImageJ.
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
Time Frame: 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.
Phosphorylation of Akt (Thr308 and Ser473) will be quantified in skeletal muscle tissue obtained at baseline and after the intervention. Levels of phosphorylated Akt and total Akt will be measured, and the outcome will be expressed as the change in the phospho-to-total Akt protein ratio 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.

Collaborators and Investigators

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

Sponsor

Jean L. Fry

Collaborators

National Institute of General Medical Sciences (NIGMS)

Investigators

  • Principal Investigator: Jean Fry, PhD, University of Kentucky

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 (Estimated)

May 4, 2026

Primary Completion (Estimated)

January 31, 2029

Study Completion (Estimated)

January 31, 2029

Study Registration Dates

First Submitted

January 7, 2026

First Submitted That Met QC Criteria

January 7, 2026

First Posted (Actual)

January 9, 2026

Study Record Updates

Last Update Posted (Actual)

April 15, 2026

Last Update Submitted That Met QC Criteria

April 10, 2026

Last Verified

January 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 108059
  • P20GM156679 (U.S. NIH Grant/Contract)

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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