Forearm Immobilization, Metabolic Health, and Muscle Loss

The Impact of Acipimox and Salbutamol Supplementation on the Development of Insulin Resistance and Anabolic Resistance During Forearm Immobilization in Healthy, Young Volunteers

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

Study Overview

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

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Devon
    • Exeter, Devon, United Kingdom
      • Royal Exeter & Devon NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 40 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percent Change in Forearm Glucose Uptake	Insulin sensitivity, measured as forearm glucose uptake, during a 30-min baseline period and 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
Percent Change in Muscle Protein Synthesis	Percent change in 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)

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): May 10, 2019
• Primary Completion (Actual): July 1, 2021
• Study Completion (Actual): July 1, 2021

Study Registration Dates

• First Submitted: February 28, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): June 21, 2024
• Last Update Submitted That Met QC Criteria: January 10, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Other Study ID Numbers: 250839; 209198/Z/17/Z (Other Grant/Funding Number: Wellcome Trust)

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
• product manufactured in and exported from the U.S.: No