NCT04461236

Brief Summary

The primary objective of this study is to determine the mechanism of reduced branched-chain amino acid (BCAA) oxidation to propionyl CoA and isoleucine intake can affect TCA cycle function in obese insulin resistant T2D. We will test the hypotheses that isoleucine and valine oxidation to propionyl CoA is reduced and that week long oral administration of isoleucine in T2D subjects will increase propionyl CoA and succinyl CoA production in muscle. The secondary objectives of this study are to determine the extent to which type 2 diabetics are capable of controlling and coordinating complex patterns of force using the upper and lower limb. This line of research has functional significance as upper body coordination and fine motor control is important for many activities associated with daily living and may contribute to therapy protocols for individuals with type 2 diabetes. Functional performance via six-minute walk and balance board measurement will also be tested with and without sensory augmentation via electrical stimulation of foot. Changes in peripheral blood mononuclear cells (PBMCs) mitochondrial respiration values will also be assessed between subject types and for diabetic after the 10-day supplementation period.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
38

participants targeted

Target at P25-P50 for not_applicable type-2-diabetes

Timeline
Completed

Started May 2019

Shorter than P25 for not_applicable type-2-diabetes

Geographic Reach
1 country

1 active site

Status
completed

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

Study Start

First participant enrolled

May 30, 2019

Completed
9 months until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 2, 2020

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

March 2, 2020

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

June 22, 2020

Completed
16 days until next milestone

First Posted

Study publicly available on registry

July 8, 2020

Completed
Last Updated

February 3, 2025

Status Verified

January 1, 2025

Enrollment Period

9 months

First QC Date

June 22, 2020

Last Update Submit

January 30, 2025

Conditions

Type 2 Diabetes

Keywords

Isoleucine intake

Outcome Measures

Primary Outcomes (1)

  • Change in whole-body protein metabolism in type 2 diabetic obese subjects

    Change in whole-body protein synthesis rate after 10 days of isoleucine supplementation

    0, 10, 20, 40, 60, 120 ± 5 min after isotope infusion

Secondary Outcomes (9)

  • 24-hour glucose levels in type 2 diabetic obese subjects

    10 days

  • Group differences in fat metabolism between type 2 diabetics and non-diabetic subjects

    0, 10, 20, 40, 60, 120 ± 5 min after isotope infusion

  • Group differences in glucose metabolism between type 2 diabetics and non-diabetic subjects

    0, 10, 20, 40, 60, 120 ± 5 min after isotope infusion

  • Changes in state of mood as measured by the Hospital Anxiety and Depression Scale (HADS) in type 2 diabetics obese subjects

    postabsorptive state on study day 1 and study day 2

  • Changes in state of mood as measured by the Profile of Mood State (POMS) in type 2 diabetics obese subjects

    postabsorptive state on study day 1 and study day 2

  • +4 more secondary outcomes

Other Outcomes (5)

  • Group differences in skeletal muscle strength between type 2 diabetics and non-diabetic subjects

    on study day 1 (baseline)

  • Group differences in balance between type 2 diabetics and non-diabetic subjects

    on study day 1 (baseline)

  • Group differences in exercise capacity between type 2 diabetics and non-diabetic subjects

    on study day 1 (baseline)

  • +2 more other outcomes

Study Arms (3)

Isoleucine

EXPERIMENTAL

Type 2 Diabetics randomized to isoleucine group

Dietary Supplement: Oral Supplement

Placebo

PLACEBO COMPARATOR

Type 2 Diabetics randomized to placebo group

Dietary Supplement: Placebo

Healthy

NO INTERVENTION

gender-, age-, BMI-matched controls for baseline measurements only. No supplementation provided.

Interventions

Oral SupplementDIETARY_SUPPLEMENT

Supplement provided in capsules. Half the capsules to be taken with lunch and the other half with dinner. All supplements are commercially available.

Isoleucine
PlaceboDIETARY_SUPPLEMENT

Placebo

Placebo

Eligibility Criteria

Age45 Years - 84 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Age: 45-84 years old, inclusive
  • Clinical diagnosis with type-II diabetes (Diabetics subjects only) and oral glucose lowering medication or insulin
  • Stable body-weight (± 5%) for the past 3 months
  • Body Mass Index (BMI): 28 kg/m2 or higher
  • Subject is judged to be in satisfactory health based on medical history, physical examination, and laboratory screening evaluations.
  • Ability to walk, sit down and stand up independently
  • Ability to lie in supine or elevated position for up to 10 hours
  • Willingness and ability to comply with the protocol

You may not qualify if:

  • Subject is expected to have surgery within one-month of screening
  • Subject is currently participating or has participated in a study with an investigational compound or device within 30 days of signing the informed consent.
  • Active dependence of alcohol or drugs
  • Diagnosed and active treatment of Type 1 Diabetes Mellitus
  • Medication: Use of substances known to influence protein metabolism: antibiotics within 3 weeks prior to the study visit, current use of corticosteroids, growth hormone, testosterone, estrogen, immunosuppressant, blood thinners, or insulin.
  • Adherence to a weight loss diet.
  • (Possible) pregnancy

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Texas A&M University CTRAL

College Station, Texas, 77845-4253, United States

Location

Related Publications (2)

  • Deutz LN, Wierzchowska-McNew RA, Deutz NE, Engelen MP. Reduced plasma glycine concentration in healthy and chronically diseased older adults: a marker of visceral adiposity? Am J Clin Nutr. 2024 Jun;119(6):1455-1464. doi: 10.1016/j.ajcnut.2024.04.008. Epub 2024 Apr 12.

    PMID: 38616018DERIVED

  • Wierzchowska-McNew RA, Engelen MPKJ, Thaden JJ, Ten Have GAM, Deutz NEP. Obesity- and sex-related metabolism of arginine and nitric oxide in adults. Am J Clin Nutr. 2022 Dec 19;116(6):1610-1620. doi: 10.1093/ajcn/nqac277.

    PMID: 36166849DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Dietary Supplements

Condition Hierarchy (Ancestors)

Diabetes MellitusGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesEndocrine System Diseases

Intervention Hierarchy (Ancestors)

FoodDiet, Food, and NutritionPhysiological PhenomenaFood and Beverages

Study Design

Study Type
interventional
Phase
not applicable
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Purpose
OTHER
Intervention Model
SINGLE GROUP
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor

Study Record Dates

First Submitted

June 22, 2020

First Posted

July 8, 2020

Study Start

May 30, 2019

Primary Completion

March 2, 2020

Study Completion

March 2, 2020

Last Updated

February 3, 2025

Record last verified: 2025-01

Locations

US(1)