Forearm Immobilization, Metabolic Health, and Nutrition

• Sponsor: University of Exeter (Other)
• Overall Status: Completed
• CT.gov ID: NCT04626401
• Collaborator: Wellcome Trust (Other)
• Enrollment: 24
• Location: 1
• Arms: 2
• Actual Duration (Months): 11.5
• Patients Per Site Per Month: 2.1

Study Details

Study Description

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

Condition or Disease	Intervention/Treatment	Phase
Healthy	Behavioral: Forearm immobilization	N/A

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Masking Description: Double blinded
• Primary Purpose: Basic Science
• 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.
• Actual Study Start Date: Jun 24, 2021
• Actual Primary Completion Date: Jun 10, 2022
• Actual Study Completion Date: Jun 10, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Forearm glucose uptake [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.]

   Insulin sensitivity, measured as forearm glucose uptake, under hyperinsulinaemic-euglycaemic conditions

Secondary Outcome Measures

1. Muscle protein synthesis rates [During 3 hours of hyperinsulinaemic-euglycaemic clamped conditions before and after 2 days of immobilisation]

   Muscle protein synthesis rates are measured using an intravenously infused stable isotope labelled amino acid tracer, combined with repeated blood and muscle tissue sampling.

2. Intramuscular BCAA concentration [Before and after 3 hours of hyperinsulinaemic-euglycaemic clamped conditions]

   Intramuscular BCAA concentration measured using mass spectrometry

3. BCAA concentrations between forearm arterialized venous and deep venous blood [Fasted and during the steady-state phase of the insulin clamp (i.e. last 30 minutes)]

   Arterialized venous-deep venous forearm balance of BCAA, in the fasted state and during a hyperinsulinaemic-euglycaemic clamp

4. Whole-body substrate oxidation [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)]

   Whole-body substrate oxidation measured using indirect calorimetry

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Exeter	Exeter	Devon	United Kingdom	EX1 2LU

Sponsors and Collaborators

• University of Exeter
• Wellcome Trust

Investigators

• Principal Investigator: Marlou Dirks, PhD, University of Exeter

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: University of Exeter
• ClinicalTrials.gov Identifier: NCT04626401
• Other Study ID Numbers: 200617
• First Posted: Nov 12, 2020
• Last Update Posted: Aug 25, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Study Results

No Results Posted as of Aug 25, 2022