Clinical trial NCT04279951: Alpha and Omega of Lifestyle Therapy
Official title: Alpha and Omega of Lifestyle Therapy - Resistance Training and Ingestion of n-3 Polyunsaturated Fatty Acids to Improve Health and Muscle Functions in Individuals With Obesity and Healthy Controls
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Obesity
Keywords: Resistance exercise
Omega 3
Lead sponsor: Inland Norway University of Applied Sciences
Sponsor class: OTHER
First posted: 2020-02-21
Enrollment: 150
Sex: ALL
Minimum age (years): 30
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: BASIC_SCIENCE

Brief summary: The study aims to investigate the effects of double-blinded, randomized placebo-controlled n3-fatty acid supplementation (1000 mg day-1) and 13 weeks of resistance training on muscle function/biology and systemic health in individuals with obesity (BMI\>30) and lean individuals (BMI\<30)

Detailed description: Lifestyle therapy is important for treating lifestyle-related morbidities such as obesity. Such therapy often includes exercise and nutrition, and leads to improved health, functionality and quality of life. Unfortunately, obesity leads to adverse changes in the physiological milieu, including inflammation and altered nutritional status such as reduced omega-3:omega-6 ratios. Indeed, inadequate omega 3 levels are common even among lean individuals. This may negatively affect the outcome of lifestyle therapy with exercise, particularly those involving resistance training, contributing to the large heterogeneity seen in training responses. In accordance with this, many individuals (including both lean and obese subjects) fail to improve muscle biology/functions and health, including failure to increase muscle mass and strength, failure to improve glucose handling and inflammatory status. This makes general lifestyle therapy recommendations ineffective. Here, we investigate effects of double-blinded, randomized placebo-controlled n3-fatty acid supplementation (1000 mg day-1) and 13 weeks of low- and high-load resistance training on muscle growth/function/biology and health in individuals with obesity (BMI\>30, n=60) and lean controls (BMI\<30, n=60). Each participant will perform two different training protocols, one on each leg. The supplement period will commence 7 weeks prior to the onset of the strength training intervention to ensure adequate omega-3 biology at the onset of training. Analyses include assessment of the separate and combined effects of n3-supplementation and obesity on training responses to resistance training, measured as muscle mass, muscle strength/functionality, muscle biological traits, and systemic health variables such as hormone/inflammation/glucose biology, adipose tissue biology/mass, gut microbiome and health-related quality of life. The project will provide important insight into the feasibility of resistance training and n-3 fatty acid supplementation for treating individuals with obesity, paving the way for personalized lifestyle therapy.

The study has two defined main outcome measures, targeting the combined effects of omega-3 and strength training on i) muscle thickness of the thigh (measured using ultrasound; this main outcome measure targets the effects of the intervention on muscle growth), and ii) glucose tolerance (measured using an oral glucose test; this main outcome measure targets the effects of the intervention on improvements in health).

In our analytical approach, we will use a mixed model-approach to assess the main effects of the intervention, mainly defined as changes from before to after the resistance training intervention. Importantly, for health variables such as glucose tolerance, analyses will be performed by accounting for individual variation at baseline, as any beneficial effect can be expected to be higher/present only in individuals with a pathological/diseased starting point. Notably, for many variables, we will collect data from two additional time points (pre-supplementation and after two weeks of familiarization to training). These data will provide insight into additional perspectives, such as the effects of omega-3 intake-only on glucose tolerance, which will bring additional depth to our conclusions (these analyses are not necessarily specified in the Outcome Measures section). For other data, such as primary cultivation of skeletal muscle and muscle mitochondrial respiration, data will only be collected from a randomized subset of participants. For analyses of the effects of the intervention on obesity-related pathophysiologies and health-related quality of life, data from a group of non-intervention individuals will act as reference values (data sampled alongside the intervention). Finally, we will use regression analyses to explain individual differences in training responses, with particular emphasis on muscle hypertrophy/glucose tolerance and their mechanistic origin of nature.

2021/08: The number of anticipated participants was increased from 120 to 150 due to circumstances relating to the SARS-CoV-2 pandemic

Eligibility criteria: Inclusion Criteria:

* Untrained (less than 2 sessions of resistance exercise per month and less than 3 hours of endurance exercise per week)

Exclusion Criteria:

* Unstable cardiovascular disease
* Injuries affecting the ability to perform heavy resistance exercise
* Mental illness
* Allergy to local anesthesia
* Smoking
* Use of medicine or drugs containing steroids the last two months prior to inclusion

Primary outcomes:
measure: Muscle thickness, ultrasound
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Glucose tolerance
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
Secondary outcomes:
measure: Lean body mass
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Fat mass
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Visceral fat mass
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle mass, MRI
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle mass, immunohistochemistry
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle mass, combined measure
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle fibre type composition
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Myonuclear number
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle satellite cell number
timeFrame: Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
measure: Muscle capillarization
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Fat infiltration (muscle)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Muscle quality
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Unilateral lower body maximal strength
timeFrame: Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
measure: Unilateral lower body isokinetic muscle strength
timeFrame: Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
measure: Unilateral lower body isometric muscle strength
timeFrame: Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
measure: Peak power output during one-legged cycling
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Oxygen consumption during one-legged cycling
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Unilateral lower body muscle endurance
timeFrame: Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
measure: Waist circumference
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Blood pressure at rest
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Hemoglobin glycosylation (HbA1c)
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Fasting blood glucose
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: N-3 PUFA (blood)
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Inflammatory characteristics of peripheral blood mononuclear cell (PBMC)
timeFrame: Throughout the course of the intervention (weeks 0, 8 and 20)
measure: Lipid concentrations in blood
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Nutritent concentrations in blood
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Hormone concentrations in blood
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Concentrations of inflammatory factors in blood
timeFrame: Changes throughout the course of the intervention (weeks 0, 8 and 20)
measure: Muscle fractional synthesis rate
timeFrame: Week 18 to 20
measure: Gene expression in skeletal muscle (intervention)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Gene expression in skeletal muscle (familiarization)
timeFrame: Changes from before to after familiarization to resistance exercise (week 8 to 10)
measure: Protein abundance in skeletal muscle (intervention)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Protein abundance in skeletal muscle (familiarization)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 10)
measure: Mitochondrial functions in muscle
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Gene expression in subcutaneous fat
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Satellite cell proliferation and myotube growth (in vitro)
timeFrame: Changes from before to after N3-supplementation-only (week 0 to 8)
measure: Musculoskeletal pain (Nordic Pain Questionnaire)
timeFrame: Changes throughout the course of the training intervention (weeks 0, 8 and 20)
measure: Musculoskeletal pain (VAS)
timeFrame: Changes throughout the course of the training intervention (weeks 0, 8 and 20)
measure: Gastrointestinal symptoms
timeFrame: Changes throughout the course of the training intervention (weeks 0, 8 and 20)
measure: Gut microbiome (feces, N3-supplementation-only)
timeFrame: Changes from before to after N3-supplementation-only (week 0 to 8)
measure: Gut microbiome (feces, training intervention)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Fecal short-chained fatty acids (N3-supplementation-only)
timeFrame: Changes from before to after N3-supplementation-only (week 0 to 8)
measure: Fecal short-chained fatty acids (training intervention)
timeFrame: Changes from before to after the resistance training intervention (week 8 to 20)
measure: Arterial stiffness
timeFrame: Throughout the course of the intervention (week 0, 8 and 20)
measure: Health-related quality of life (SF-36)
timeFrame: Changes throughout the course of the intervention (week 0, 8 and 20)
measure: Health-related quality of life in overweight/obesity
timeFrame: Changes throughout the course of the intervention (week 0, 8 and 20)
measure: Health-related quality of life (PANAS)
timeFrame: Changes throughout the course of the intervention (week 0, 8 and 20)
measure: Activities of daily living
timeFrame: Changes throughout the course of the intervention (week 0, 8 and 20)
Other outcomes:
measure: Training diary relating to the intervention protocol
timeFrame: Weeks 8 to 20
measure: Dietary registration
timeFrame: Week 0, 8 and 20
Locations:
city: Lillehammer
country: Norway
facility: Inland Norway University of Applied Sciences
Study officials:
affiliation: Inland Norway University of Applied Sciences
name: Stian Ellefsen, PhD
role: PRINCIPAL_INVESTIGATOR
References: