Alpha and Omega of Lifestyle Therapy

Obesity Clinical Trial

— Alpha&Omega  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04279951
• Other study ID #: Trainome 2019#015
• Status: Active, not recruiting
• Phase: N/A
• Start date: September 2, 2019
• Est. completion date: December 2026

Study information

• Verified date: August 2022
• Source: Inland Norway University of Applied Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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)

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

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 150
• Est. completion date: December 2026
• Est. primary completion date: March 30, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 60 Years

Eligibility

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

Related Conditions & MeSH terms

• Obesity

Intervention

Other:
• Resistance exercise
High-load and low-load resistance exercise two times per week for 10 weeks, preceded by 3 weeks of familiarization to training (high-load training)

Dietary Supplement:
• Omega-3
1 gram of omega-3 per day for 20 weeks
• Placebo
1 gram of sunflower oleic oil per day for 20 weeks

Locations

Country	Name	City	State
Norway	Inland Norway University of Applied Sciences	Lillehammer

Sponsors (1)

Lead Sponsor	Collaborator
Inland Norway University of Applied Sciences

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Training diary relating to the intervention protocol	Information about intervention-specific training, including training frequency, volume and load	Weeks 8 to 20
Other	Dietary registration	Dietary registration measured using a food frequency questionnaire, assessing nutritional composition, energy intake and habitual patterns of dietary intake	Week 0, 8 and 20
Primary	Muscle thickness, ultrasound	Muscle thickness of vastus lateralis and vastus intermedius measured using ultrasound	Changes from before to after the resistance training intervention (week 8 to 20)
Primary	Glucose tolerance	Glucose tolerance measured using an oral glucose tolerance test	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Lean body mass	Lean body mass measured using whole-body DXA scan	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Fat mass	Fat mass measured using whole-body DXA scan	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Visceral fat mass	Visceral fat mass measured using whole-body DXA scan	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle mass, MRI	Thigh muscle cross sectional area/volume measured using magnetic resonance imaging (MRI)	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle mass, immunohistochemistry	Fibre type-specific muscle-fibre cross-sectional area measured using immunohistochemistry	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle mass, combined measure	Muscle mass of the legs measured as the weighted average of data from ultrasound, MRI, immunohistochemistry and DXA measurements	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle fibre type composition	Muscle fibre type composition measured using immunohistochemistry	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Myonuclear number	Fiber type-specific myonuclear number measured using immunohistochemistry	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle satellite cell number	Fiber type-specific muscle satellite cell number measured using immunohistochemistry	Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
Secondary	Muscle capillarization	Fiber type-specific muscle capillarization measured using immunohistochemistry	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Fat infiltration (muscle)	Fat infiltration in thigh muscle measured using magnetic resonance imaging (MRI)	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Muscle quality	Muscle strength measured per muscle mass of the legs	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Unilateral lower body maximal strength	The ability of muscles of the lower body to exert maximal force during dynamic movements	Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
Secondary	Unilateral lower body isokinetic muscle strength	The ability of the knee extensors to exert maximal force during isokinetic movements	Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
Secondary	Unilateral lower body isometric muscle strength	The ability of the knee extensors to exert maximal force during isometric actions	Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
Secondary	Peak power output during one-legged cycling	Maximal cycling performance measured as peak power output (Watt) during an incremental one-legged cycling test	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Oxygen consumption during one-legged cycling	The ability to consume oxygen during an incremental one-legged cycling test	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Unilateral lower body muscle endurance	The ability of muscles of the lower body to perform repeated dynamic contractions at a specified submaximal load (70% of 1RM) to exhaustion	Changes throughout the course of the resistance training intervention (weeks 8, 10 and 20)
Secondary	Waist circumference	Circumference of the waist measured using measuring tape	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Blood pressure at rest	Blood pressure at rest measured using an automated upper-arm blood pressure cuff	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Hemoglobin glycosylation (HbA1c)	Long-term glucose levels measured as hemoglobin glycosylation of the metabolic syndrome such as waist circumference, blood pressure at rest, lipid profile ( hemoglobin glycosylation (HbA1c) and fasting blood glucose	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Fasting blood glucose	Fasting blood glucose measured in serum	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	N-3 PUFA (blood)	Omega-3 (DHA/EPA) levels in blood	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Inflammatory characteristics of peripheral blood mononuclear cell (PBMC)	Expression of genes associated with inflammation and lipid metabolism in peripheral blood mononuclear cell measured using quantitative PCR	Throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Lipid concentrations in blood	Concentrations of various lipids and lipid metabolites such as triglycerides, LDL, HDL, ceramides, dihydroceramides, glucosylceramides, and lactosylceramides measured in serum using tageted metabolomics	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Nutritent concentrations in blood	Concentrations of nutrients (such as amino acids) and ions (such as iron and calcium) measured in serum	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Hormone concentrations in blood	Concentrations of hormones such as testosterone, growth hormone, thyroid hormones, cortisol and insulin (as well as c-peptide) measured in serum	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Concentrations of inflammatory factors in blood	Levels of inflammatory factors such as IL6, CRP and NFkB in serum	Changes throughout the course of the intervention (weeks 0, 8 and 20)
Secondary	Muscle fractional synthesis rate	Protein/RNA synthesis rate measured using heavy water (deuterium) and chromatography/spectrometry	Week 18 to 20
Secondary	Gene expression in skeletal muscle (intervention)	RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as targeted genes and at the level of the transcriptome	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Gene expression in skeletal muscle (familiarization)	RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in m. vastus lateralis, measured both as single genes and at the level of the transcriptome	Changes from before to after familiarization to resistance exercise (week 8 to 10)
Secondary	Protein abundance in skeletal muscle (intervention)	Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Protein abundance in skeletal muscle (familiarization)	Levels of proteins and their modification status (e.g. phosphorylation) in m. vastus lateralis, measured at the level of single proteins and at the level of the proteome	Changes from before to after the resistance training intervention (week 8 to 10)
Secondary	Mitochondrial functions in muscle	The ability of muscle mitochondria (extracted from muscle homogenate) to synthesize ATP in vitro	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Gene expression in subcutaneous fat	RNA (e.g. messenger RNA, ribosomal RNA, microRNA, long non-coding RNA) abundances in subcutaneous fat, measured as targeted genes	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Satellite cell proliferation and myotube growth (in vitro)	The ability of muscle satellite cells (extracted from muscle homogenate) to proliferate (rates of cell division), differentiate into myotubes and subsequently grow (rates of change in myotube size) in primary cultures	Changes from before to after N3-supplementation-only (week 0 to 8)
Secondary	Musculoskeletal pain (Nordic Pain Questionnaire)	Musculoskeletal pain measured using The standardized Nordic Pain Questionnaire	Changes throughout the course of the training intervention (weeks 0, 8 and 20)
Secondary	Musculoskeletal pain (VAS)	Musculoskeletal pain measured using VAS-scale (1-10)	Changes throughout the course of the training intervention (weeks 0, 8 and 20)
Secondary	Gastrointestinal symptoms	Gastrointestinal symptoms such as abdominal discomfort and pain, measured using Rome IV criteria	Changes throughout the course of the training intervention (weeks 0, 8 and 20)
Secondary	Gut microbiome (feces, N3-supplementation-only)	Relative composition of the gut microbiome measured using quantitative polymerase chain reaction	Changes from before to after N3-supplementation-only (week 0 to 8)
Secondary	Gut microbiome (feces, training intervention)	Relative composition of the gut microbiome measured using quantitative polymerase chain reaction	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Fecal short-chained fatty acids (N3-supplementation-only)	Short chained fatty acids measured in feces	Changes from before to after N3-supplementation-only (week 0 to 8)
Secondary	Fecal short-chained fatty acids (training intervention)	Short chained fatty acids measured in feces	Changes from before to after the resistance training intervention (week 8 to 20)
Secondary	Arterial stiffness	Arterial stiffness measured using pulse-wave velocity	Throughout the course of the intervention (week 0, 8 and 20)
Secondary	Health-related quality of life (SF-36)	Health-related quality of life measured using the SF-36 questionnaire	Changes throughout the course of the intervention (week 0, 8 and 20)
Secondary	Health-related quality of life in overweight/obesity	Health-related quality of life in overweight/obesity individuals measured using The impact of weight on quality of life (IWQOL) questionnaire	Changes throughout the course of the intervention (week 0, 8 and 20)
Secondary	Health-related quality of life (PANAS)	Health-related quality of life measured using the Positive and Negative Affect Schedule (PANAS) questionnaire	Changes throughout the course of the intervention (week 0, 8 and 20)
Secondary	Activities of daily living	Activities of daily living (e.g. time spent in physical activity, intensities of activities) measured using questionnaire	Changes throughout the course of the intervention (week 0, 8 and 20)