Forearm Immobilization, Metabolic Health, and Nutrition

The Impact of Dietary Branched-chain Amino Acid (BCAA) Restriction on the Development of Insulin Resistance and Anabolic Resistance During Forearm Immobilization in Healthy, Young Volunteers.

The present study will investigate the impact of dietary branched chain amino acid restriction on muscle atrophy, insulin sensitivity and muscle protein synthesis following short-term forearm immobilization

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Behavioral: Forearm immobilization

Detailed Description

Twenty-four healthy young volunteers will undergo 2 days of forearm immobilization in combination with either a branched chain amino acid restricted diet or a control diet. Before and after immobilization, they will receive a stable isotope tracer infusion (5.5 h) combined with repeated blood and muscle sampling under insulin clamp conditions, in order to measure insulin sensitivity and muscle protein synthesis in the fasted and fed state.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom, EX1 2LU
      • University of Exeter

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Males and females 18-40 years of age
• Body mass index between 18.5 and 30 kg/m2

Exclusion Criteria:

• Smoking
• Any diagnosed metabolic impairment (e.g. type 1 or 2 diabetes)
• Any diagnosed cardiovascular disease
• Hypertension (≥140 mmHg systolic and/or ≥90 mmHg diastolic)
• Chronic use of any prescribed or over the counter pharmaceuticals (excluding oral contraceptives and contraceptive devices)
• Regular use of nutritional supplements
• Currently involved in a structured progressive resistance training programme (>3 times per week)
• A personal or family history of thrombosis, epilepsy, seizures or schizophrenia
• Any previous motor disorders or disorders in muscle and/or lipid metabolism
• Known hypokalaemia
• Presence of an ulcer in the stomach or gut and/or strong history of indigestion
• Known severe kidney problems
• Pregnant or breastfeeding
• Unable to give consent

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Control diet during immobilisation; A 2 day controlled dietary intervention.	Behavioral: Forearm immobilization; Two days of forearm immobilization
Experimental: Branched chain amino acid restricted diet during immobilisation; A 2 day branched chain amino acid restricted dietary intervention.	Behavioral: Forearm immobilization; Two days of forearm immobilization

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Forearm glucose uptake	Insulin sensitivity, measured as forearm glucose uptake, under hyperinsulinaemic-euglycaemic conditions	Hyperinsulinaemic-euglycaemic clamps are performed before and immediately after 2 days of forearm immobilisation. Forearm glucose uptake is measured during the steady state period of the clamp.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis rates	Muscle protein synthesis rates are measured using an intravenously infused stable isotope labelled amino acid tracer, combined with repeated blood and muscle tissue sampling.	During 3 hours of hyperinsulinaemic-euglycaemic clamped conditions before and after 2 days of immobilisation
Intramuscular BCAA concentration	Intramuscular BCAA concentration measured using mass spectrometry	Before and after 3 hours of hyperinsulinaemic-euglycaemic clamped conditions
BCAA concentrations between forearm arterialized venous and deep venous blood	Arterialized venous-deep venous forearm balance of BCAA, in the fasted state and during a hyperinsulinaemic-euglycaemic clamp	Fasted and during the steady-state phase of the insulin clamp (i.e. last 30 minutes)
Whole-body substrate oxidation	Whole-body substrate oxidation measured using indirect calorimetry	Hyperinsulinaemic-euglycaemic clamps are performed before and immediately after 2 days of forearm immobilisation. Whole-body substrate oxidation is measured before the commencement of, and during the steady state period of the clamp (last 30 minutes)

Collaborators and Investigators

• Sponsor: University of Exeter
• Collaborators: Wellcome Trust
• Investigators: Principal Investigator: Marlou Dirks, PhD, University of Exeter

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2021
• Primary Completion (Actual): June 10, 2022
• Study Completion (Actual): June 10, 2022

Study Registration Dates

• First Submitted: October 22, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): August 25, 2022
• Last Update Submitted That Met QC Criteria: August 24, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: 200617

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