Mechanisms of Tissue Repair After Muscle Injury and Tendon Strain

Regulation of Human Tendon and Skeletal Muscle Protein Turnover Following Tissue Injury: Mechanisms Behind Regeneration and Injury Preventive Adaptations

The study is a 5-week human study including 24 18-35 year old healthy men. Each participant will have muscle injury and tendon strain induced in one leg using neuromuscular electrical stimulation in conjunction with forced lengthening contractions. The investigators will monitor the recovery from injury/strain over a 4 week period, in which half of the subjects will receive growth hormone (somatropin) to stimulate the connective tissue synthesis.

Study Overview

• Status: Completed
• Conditions: Muscle; Injury, Quadriceps (Thigh); Tendon Strain
• Intervention / Treatment: Other: Neuromuscular electrical stimulation

• Study Type: Interventional
• Enrollment (Actual): 25
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen, Denmark, 2400
    • Institute of Sports Medicine Copenhagen

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Healthy men
• BMI between 18.5-30 kg/m^2

Exclusion Criteria:

• Smoking
• Regular strength training within the last 3 months
• Current or former use of anabolic steroids or growth hormone
• Use of corticosteroids in the last 3 months
• Use of blood thinning medication
• Use of medication which can affect muscle protein synthesis
• Current or former drug og alcohol abuse
• Knee pain
• Previous participation in studies using deuterated water or alanine tracers

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Growth hormone/somatropin; Somatropin over two weeks (33.3 ug/kg/day in the first week, 50 ug/kg/day in the second week)	Other: Neuromuscular electrical stimulation; One bout of neuromuscular electrical stimulation in conjunction with forced lengthening contractions on one leg; Other Names: Neuromuscular electrical stimulation using Theta 4 channel stimulator from Chattanooga. Coupled with forced eccentric contractions.
Placebo Comparator: Placebo; Injections of placebo/saline over two weeks	Other: Neuromuscular electrical stimulation; One bout of neuromuscular electrical stimulation in conjunction with forced lengthening contractions on one leg; Other Names: Neuromuscular electrical stimulation using Theta 4 channel stimulator from Chattanooga. Coupled with forced eccentric contractions.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Effect of somatropin on muscle protein synthesis 14 days after injury	The difference in fractional synthesis rate in muscle proteins 14 days after injury with or without 14 days treatment with somatropin. Measured using deuterated water	14 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle protein synthesis 7 days after injury	The difference in fractional synthesis rate in muscle proteins 7 days after injury vs control (no injury) with or without 7 days treatment with somatropin. Measured using deuterated water	7 days
Muscle protein synthesis 14 days after injury	The difference in fractional synthesis rate in muscle proteins 14 days after injury compared to control leg (no injury). Measured using deuterated water.	14 days
Muscle protein breakdown 14 days after injury	The difference in fractional synthesis rate in muscle proteins 14 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. Measured using stable isotop labelled alanine.	14 days
Muscle protein breakdown 7 days after injury	The difference in fractional synthesis rate in muscle proteins 7 days after injury vs. control (no injury) with or without 7 days treatment with somatropin. Measured using stable isotop labelled alanine.	7 days
Muscle protein breakdown 28 days after injury	The difference in fractional synthesis rate in muscle proteins 28 days after injury vs. control (no injury) with or without 14 days treatment with somatropin. Measured using stable isotop labelled alanine.	28 days
Histochemical staining of muscle cross sections 7 days after injury	Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections	7 days
Histochemical staining of muscle cross sections 14 days after injury	Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections	14 days
Histochemical staining of muscle cross sections 28 days after injury	Number of satellite cells, fibroblasts and immune cells in injured vs. control tissue (no injury), with and without growth hormone. Measured using histochemical staining of muscle cross sections	28 days
The effect of somatropin on tendon tissue synthesis	The difference in fractional synthesis rate in tendon proteins after 7 days placebo/treatment with somatropin. Measured using deuterated water	7 days
Tendon tissue synthesis 7 days after strain	The difference in fractional synthesis rate in tendon proteins 7 days after strain compared to control leg (no strain). Measured using deuterated water	7 days
Tendon tissue synthesis 7 days after strain with/without somatropin	The difference in fractional synthesis rate in tendon proteins 7 days after strain compared to control leg (no strain) with or without somatropin. Measured using deuterated water	7 days
Isometric muscle force output 7 days following injury	The difference in isometric muscle force output 7 days after injury vs. control (no injury) with or without 7 days treatment with somatropin.	7 days
Isometric muscle force output 14 days following injury	The difference in isometric muscle force output 14 days after injury vs. control (no injury) with or without 14 days treatment with somatropin.	14 days
Isometric muscle force output 28 days following injury	The difference in isometric muscle force output 28 days after injury vs. control (no injury) with or without 14 days treatment with somatropin.	28 days

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 11, 2023
• Primary Completion (Actual): January 3, 2024
• Study Completion (Actual): January 3, 2024

Study Registration Dates

• First Submitted: March 17, 2023
• First Submitted That Met QC Criteria: March 30, 2023
• First Posted (Actual): April 12, 2023

Study Record Updates

• Last Update Posted (Actual): January 9, 2024
• Last Update Submitted That Met QC Criteria: January 8, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Wounds and Injuries; Sprains and Strains
• Other Study ID Numbers: BBH150

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The IPD will be made available upon individual request once the study is finalised and published.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No