## Protocol Section
### Identification Module
**NCT ID:** NCT05063279

**Acronym:** RELIEF

**Brief Title:** RELIEF - Resistance Training for Life

**Official Title:** Resistance Training for Life - the Efficacy of Increasing Resistance Training Volume for Improving Muscle Mass, Function, Biology and Health in Young and Elderly

#### Organization Study ID Info
**ID:** TR030
#### Organization
**Class:** OTHER
**Full Name:** Inland Norway University of Applied Sciences
### Status Module
#### Completion Date
**Date:** 2022-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2022-08-08

**Type:** ACTUAL

**Last Update Submit Date:** 2022-08-05

**Overall Status:** RECRUITING

#### Primary Completion Date
**Date:** 2022-12-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2021-09-06

**Type:** ACTUAL

**Status Verified Date:** 2022-08

#### Study First Post Date
**Date:** 2021-10-01
**Type:** ACTUAL
**Study First Submit Date:** 2021-09-11
**Study First Submit QC Date:** 2021-09-27
### Sponsor Collaborators Module

#### Collaborators

**Class:** OTHER

**Name:** Sykehuset Innlandet HF

#### Lead Sponsor

**Class:** OTHER

**Name:** Stian Ellefsen

#### Responsible Party

**Investigator Affiliation:** Inland Norway University of Applied Sciences

**Investigator Full Name:** Stian Ellefsen

**Investigator Title:** Professor

**Type:** SPONSOR_INVESTIGATOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** Sarcopenia is an age-related gradual loss of muscle mass and strength and is associated with physical disability and mortality risk. Currently, the most promising remedy for preventing and treating sarcopenia is physical activity, particularly progressive resistance training. Yet, the amount of resistance exercise needed to achieve optimal benefits remains largely unknown. This lack of knowledge is underpinned by the notion that aging reduces the ability to adapt to (and benefit from) resistance training, and is further complicated by a relative large degrees of between-subject heterogeneity. The primary aim of the study is to compare the effects of 10 weeks of resistance training with low- and moderate volume (one vs. three sets per exercise) on muscle mass accretion in lower and upper body extremities in young (\<30 years of age) and elderly individuals (\>70 years of age). Specifically, the study addresses the hypothesis that elderly individuals will benefit more from higher exercise volume (moderate vs. low) compared to their young counterparts. In addition, the study aims to compare the efficacy of the two volume conditions for altering other characteristics such as muscle strength and biology, including assessment of associations between individual changes in muscle mass, strength and biology (e.g. the relationship between muscle mass accretion and muscle content of rRNA/rDNA), and also to investigate the general health effects of the intervention.

### Conditions Module

**Conditions:**

- Sarcopenia

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** CROSSOVER

**Intervention Model Description:** Study conditions (exercise volume) are randomized to either leg/arm for within-participant comparisons. The effect of age is assessed from two parallel age groups.

##### Masking Info

**Masking:** DOUBLE

**Masking Description:** Study conditions (exercise volume) and age groups identifiers are omitted from outcome assessments whenever possible. Assessment of the primary (and selected secondary) outcome(s) will be performed in a blinded fashion by assessors/investigators.

**Who Masked:**

- INVESTIGATOR

- OUTCOMES_ASSESSOR

**Primary Purpose:** PREVENTION

#### Enrollment Info

**Count:** 60

**Type:** ESTIMATED

**Phases:**

- NA

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Participants in two age groups will receive moderate (three sets of per exercise per session) and low-volume (one set of resistance per session) training allocated to either right or left upper- and lower extremities. A total of 24 sessions will be performed over 10-12 weeks.

**Intervention Names:**

- Other: Progressive resistance training

**Label:** Resistance training group

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** A negative control group is included in the study which will not receive any resistance training.

**Label:** Negative control group

**Type:** NO_INTERVENTION

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Resistance training group

**Description:** Progressive resistance training, performed with a target number of repetitions of 10 per set. Sets are performed to exhaustion, and external load will be adjusted to meet the target number of repetitions.

**Name:** Progressive resistance training

**Type:** OTHER

### Outcomes Module

#### Other Outcomes

**Description:** Musle thickness of m. vastus lateralis measured using ultrasound

**Measure:** Muscle thickness, m. vastus lateralis (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Muscle strength will be assessed as a weighted average of lower body isokinetic and isometric knee extensor maximal force

**Measure:** Muscle strength, lower-body extremities (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Muscle strength of the arms measured as isometric force (elbow flexors; fixed angle)

**Measure:** Muscle strength, upper-body extremities (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Muscular peak power/force measured using dynamic leg press

**Measure:** Muscular peak power/force, lower-body extremities

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Muscle architecture pennation angle of m. vastus lateralis measured using ultrasound

**Measure:** Muscle architecture, m. vastus lateralis (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Muscle architecture pennation angle of m. vastus lateralis measured using ultrasound

**Measure:** Muscle architecture, m. vastus lateralis

**Time Frame:** Change from baseline to the training period (10-12 weeks).

**Description:** Whole Body Dual X-Ray Absorptiometry to estimate lean mass, bone mineral density and fat mass.

**Measure:** Body composition

**Time Frame:** Change from baseline to after the training period (10-12 weeks).

**Description:** Muscle fiber characteristics such as muscle fiber proportions, cross-sectional area, myonuclei content and capillarization measured in biopsies from m. vastus lateralis

**Measure:** Muscle fibre characteristics in m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Total-RNA abundance measured in biopsies from m. vastus lateralis.

**Measure:** Total-RNA abundance in m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Total-RNA abundance measured in biopsies from m. vastus lateralis.

**Measure:** Total-RNA abundance in m. vastus lateralis

**Time Frame:** Change from baseline to after 6 training sessions

**Description:** rRNA/RNA abundances measured in biopsies from m. vastus lateralis.

**Measure:** rRNA/RNA abundances in m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** rRNA/RNA abundances measured in biopsies from m. vastus lateralis.

**Measure:** rRNA/mRNA abundances in m. vastus lateralis

**Time Frame:** Change from baseline to after 6 training sessions

**Description:** Protein abundances measured in biopsies from m. vastus lateralis.

**Measure:** Protein abundances in m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Protein abundances measured in biopsies from m. vastus lateralis.

**Measure:** Protein abundance in m. vastus lateralis

**Time Frame:** Change from baseline to after 6 training sessions

**Description:** Ribosomal DNA content measured in m. vastus lateralis

**Measure:** rDNA content in m. vastus lateralis

**Time Frame:** Measured at baseline

**Description:** Ribosomal DNA content measured in m. vastus lateralis

**Measure:** rDNA content in m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Ribosomal DNA content measured in m. vastus lateralis

**Measure:** rDNA content in m. vastus lateralis, (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Ribosomal DNA content measured in whole-blood

**Measure:** rDNA content, whole-blood

**Time Frame:** Measured at baseline

**Description:** Ribosomal DNA content measured in whole-blood

**Measure:** rDNA content, whole-blood

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Ribosomal DNA content measured in whole-blood

**Measure:** rDNA content, whole-blood (mid)

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Epigenetic traits measured as DNA methylation/histone modifications in m. vastus lateralis

**Measure:** Epigenetic traits, muscle

**Time Frame:** Measured at baseline

**Description:** Epigenetic traits measured as DNA methylation/histone modifications in m. vastus lateralis

**Measure:** Epigenetic traits, muscle

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Epigenetic traits measured as DNA methylation/histone modifications in m. vastus lateralis

**Measure:** Epigenetic traits, muscle

**Time Frame:** Change from baseline to after 12 sessions

**Description:** Resting blood pressure

**Measure:** Blood pressure

**Time Frame:** Change from baseline to after the training period (10-12 weeks).

**Description:** Total hemoglobin mass measured using the carbon monoxide rebreathing method

**Measure:** Hemoglobin mass

**Time Frame:** Change from baseline to after the training period (10-12 weeks).

**Description:** Blood glucose and endocrine responses to a 2h glucose tolerance test (75 g bolus of glucose).

**Measure:** Glucose tolerance

**Time Frame:** Change from baseline to after the training period (10-12 weeks).

**Description:** Systemic inflammation measured as blood markers such as C-reactive protein (CRP) in resting blood samples.

**Measure:** Systemic inflammation

**Time Frame:** Change from baseline to after the training period (10-12 weeks).

**Description:** Concentrations of various lipoproteins and lipids in blood measured using targeted metabolomics

**Measure:** Lipoproteins and lipids in blood

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Long-term glucose levels measured as hemoglobin glycosylation

**Measure:** Hemoglobin glycosylation

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Concentrations of hormones such as testosterone, growth hormone, thyroid hormones, cortisol and insulin (c-peptide) in serum

**Measure:** Hormone concentrations in blood

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Health-related quality of life measured using the SF-36 questionnaire

**Measure:** Health-related quality of life (SF-36)

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Sarcopenia score assessed using SARC-F (questionnaire)

**Measure:** SARC-F

**Time Frame:** Measured at baseline

**Description:** Sarcopenia score assessed using SARC-F (questionnaire)

**Measure:** SARC-F

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Dietary composition assessed using a food-frequency questionnaire (nutritional composition, energy intake, habitual patterns of dietary intake)

**Measure:** Dietary registration

**Time Frame:** Measured at baseline

**Description:** Dietary composition assessed using a food-frequency questionnaire (nutritional composition, energy intake, habitual patterns of dietary intake)

**Measure:** Dietary registration

**Time Frame:** Measured after 12 sessions

**Description:** Information about intervention-specific training, including training frequency, volume and load

**Measure:** Training diary relating to the intervention protocol

**Time Frame:** Throughout the intervention (continuous)

**Description:** Activities of daily living measured using a questionnaire (i.e. time spent in activity, intensities and type of activity)

**Measure:** Activities of daily living (questionnaire)

**Time Frame:** Measured at baseline

**Description:** Daily activity level registred over three to five days using an accelerometer.

**Measure:** Daily activity level

**Time Frame:** Measured during the intervention

#### Primary Outcomes

**Description:** Muscle size of lower extremity knee extensors measured with magnetic resonance imaging (MRI).

**Measure:** Muscle size, lower extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

#### Secondary Outcomes

**Description:** Muscle size of upper extremity elbow flexors measured with magnetic resonance imaging (MRI).

**Measure:** Muscle size, upper-body extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Appendicular lean mass of the legs measured using Dual X-Ray Absorptiometry

**Measure:** Appendicular lean mass, lower-body extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Appendicular lean mass of the arms measured using Dual X-Ray Absorptiometry

**Measure:** Appendicular lean mass, upper-body extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Musle thickness of m. vastus lateralis measured using ultrasound

**Measure:** Muscle thickness, m. vastus lateralis

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Muscle strength of the legs measured as a weighted average of lower body isokinetic and isometric knee extensor maximal force

**Measure:** Muscle strength, lower-body extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Muscle strength of the arms measured as isometric force (elbow flexors; fixed angle)

**Measure:** Muscle strength, upper-body extremities

**Time Frame:** Change from baseline to after the training period (10-12 weeks)

**Description:** Muscular peak power/force measured using dynamic leg press

**Measure:** Muscular peak power/force, lower-body extremities

**Time Frame:** MeasurChange from baseline to after the training period (10-12 weeks)

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* Ages between 18 and 30 or \> 70

Exclusion Criteria:

* Resistance training, \> 1 session per week
* Endurance training, \> 3 sessions per week
* Unstable cardiovascular disease
* Illness or serious injury contradicting resistance training
* Serious mental illness
* Allergy to local anaesthesia

**Healthy Volunteers:** True

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** daniel.hammarstrom@inn.no

**Name:** Daniel Hammarström, PhD

**Phone:** +4740555928

**Role:** CONTACT

**Contact 2:**

**Email:** stian.ellefsen@inn.no

**Name:** Stian Ellefsen, PhD

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Lillehammer

**Contacts:**

***Contact 1:***

- **Email:** daniel.hammarstrom@inn.no

- **Name:** Daniel Hammarström, PhD

- **Phone:** +4740555928

- **Role:** CONTACT

**Country:** Norway

**Facility:** Inland Norway University of Applied Sciences

**Status:** RECRUITING

**Zip:** 2624

#### Overall Officials

**Official 1:**

**Affiliation:** Inland Norway University of Applied Sciences

**Name:** Stian Ellefsen, PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Description:** The full data sets used to analyze study outcomes will be made available with the publication of the study. Data sets will be included or referred to in the publication and hosted online.

**Info Types:**

- STUDY_PROTOCOL

- ANALYTIC_CODE

**IPD Sharing:** YES

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000009133

- Term: Muscular Atrophy

- ID: D000020879

- Term: Neuromuscular Manifestations

- ID: D000009461

- Term: Neurologic Manifestations

- ID: D000009422

- Term: Nervous System Diseases

- ID: D000001284

- Term: Atrophy

- ID: D000020763

- Term: Pathological Conditions, Anatomical

### Condition Browse Module - Browse Branches

- Abbrev: BC10

- Name: Nervous System Diseases

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: All

- Name: All Conditions

### Condition Browse Module - Browse Leaves

- ID: M28396

- Name: Sarcopenia

- Relevance: HIGH

- As Found: Sarcopenia

- ID: M12090

- Name: Muscular Atrophy

- Relevance: LOW

- As Found: Unknown

- ID: M4589

- Name: Atrophy

- Relevance: LOW

- As Found: Unknown

- ID: M22619

- Name: Neuromuscular Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M12404

- Name: Neurologic Manifestations

- Relevance: LOW

- As Found: Unknown

- ID: M22519

- Name: Pathological Conditions, Anatomical

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000055948

- Term: Sarcopenia

### Misc Info Module

- Version Holder: 2024-05-24
