Forearm Immobilization, Metabolic Health, and Nutrition

Study Overview
=================
Brief Summary
-----------------
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

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.

Official Title
-----------------
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.

Conditions
-----------------
Healthy

Intervention / Treatment
-----------------
* Behavioral: Forearm immobilization


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

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

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) |