Forearm Immobilization, Metabolic Health, and Muscle Loss

Study Overview
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Brief Summary
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The present study will investigate the impact of altered substrate availability on muscle atrophy, insulin sensitivity and muscle protein synthesis following short-term forearm immobilization

Detailed Description
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Thirty-six healthy young volunteers will undergo 2 days of forearm immobilization combined with ingestion of one of two drug or placebo. 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
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The Impact of Acipimox and Salbutamol Supplementation on the Development of Insulin Resistance and Anabolic Resistance During Forearm Immobilization in Healthy, Young Volunteers

Conditions
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Healthy

Intervention / Treatment
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* Behavioral: Forearm immobilization


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females 18-40 years of age Body mass index between 18 and 27 Exclusion Criteria: 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 Metallic implants A personal or family history of thrombosis, epilepsy, seizures or schizophrenia Any previous motor disorders Any known disorders in lipid metabolism Any known disorders in muscle metabolism Known allergy for Acipimox, beta agonist, or other substances in the tablets Known sensitivity for sympathomimetic drugs Known hypokalaemia Presence of an ulcer in the stomach or gut and/or strong history of indigestion Known severe kidney problems Pregnancy Unable to give consent

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Acipimox ingestion during immobilization<br>Oral ingestion of Acipimox during 2 days of forearm immobilization | Behavioral: Forearm immobilization<br>* Two days of forearm immobilization<br>|
| Experimental: B-agonist during immobilization<br>Oral ingestion of salbutamol during 2 days of forearm immobilization | Behavioral: Forearm immobilization<br>* Two days of forearm immobilization<br>|
| Placebo Comparator: Placebo ingestion during immobilization<br>Oral ingestion of a placebo 2 days of forearm immobilization | Behavioral: Forearm immobilization<br>* Two days of forearm immobilization<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forearm glucose uptake | Insulin sensitivity, measured as forearm glucose uptake, under hyperinsulinaemic-euglycaemic conditions | During the steady-state phase of the insulin clamp (i.e. last 30 min) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Muscle protein synthesis | Muscle protein synthesis, measured as using the arteriovenous-venous method, via stable isotope tracer infusion | In the fasted state (30 min before starting insulin clamp), and during the steady-state phase of the insulin clamp (i.e. last 30 min) | 
| Forearm muscle volume | Forearm muscle volume measured via MRI | Following cast application, and immediately after 2 days of forearm immobilizaiton |