The Impact of Exercise / Stress Stimuli on HMB Supplementation Efficacy

Supplementation Clinical Trial

Official title:

Evaluation of the Impact of Exercise / Stress Stimuli on the Mechanisms and Efficacy of Beta-hydroxy-beta-methylbutyric Acid (HMB) in Trained and Malnourished Subjects

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05444959
• Other study ID #: ZDS2022_0001
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: September 10, 2021
• Est. completion date: July 1, 2024

Study information

• Verified date: April 2024
• Source: Poznan University of Physical Education
• Contact: Krzysztof Durkalec-Michalski, Prof., PhD
• Phone: +48 61 835 51 65
• Email: durkalec-michalski[@]awf.poznan.pl
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The study aims at assessing the influence of β-hydroxy-β-methylbutyrate (HMB) free acid supplementation (90 mg/kg of fat free body mass/day) supplemented for 21 days on protein kinases activity and selected hormones levels, and subsequent improvements in muscle protein synthesis, lean body mass content and aerobic capacity.

Description:

The main aim of the project is to assess the effects of 21 days of HMB (90 mg/kg of fat free body mass per day) or Placebo (PLA) supplementation under two distinct exercise/stress stimulus conditions in the groups of exercise trained participants (S group) and individuals showing features of malnutrition (W group) on the activity of Akt/PBK/mTOR/p70S6K and MAPK/ERK protein kinase pathway in peripheral blood mononuclear cells and muscle; blood concentrations of free and total testosterone, cortisol, IGF-1 and growth hormone; level of resting and exercise energy metabolism rate and alternations in energy sources utilization during exercise, as well as aerobic capacity and body composition.

The study is a double-blind, randomized, placebo-controlled, parallel-group trial. The study protocol consists of two 21-days supplementation periods. Within the first period of the trial the participants will follow their customary physical exercise (S group) / lifestyle (W group). In turn, in the second period of the trial the routine training (S group) or customary lifestyle (W group) will be supplemented twice a week with a functional training program, as a source of an additional exercise/stress stimulus.

Investigators aim to recruit 60 exercise trained individuals (S group) and 60 will be inactive individuals showing features of malnutrition (W group). Random allocation of participants to the HMB and PLA treatments will be done using a random sequence generator, with groups being equalised by fat-free mass level (within S group and W group separately).

At the first preliminary visit anthropometric measurements, and familiarization with exercise test procedures [i.e., incremental cycling test with ergorespirometry, maximal voluntary isometric contraction test (MVIC; performed in a Biodex isokinetic dynamometer)] will be performed. After the completion of the preliminary tests, the participants within S group and W group will be divided randomly into two treatments: 90mg/kgFFM per day of HMB or the same amount of PLA. There will be two 21-days supplementation periods differing in the type of exercise/stress stimulus of the organism.

Before the start of supplementation period (T1) and after their completion (T2 and T3) the series of testing procedures will be performed, each of the series will consist of one day. Each testing series (T1, T2, and T3) will include anthropometric measurements followed by pre-exercise (pre-Ex) blood collection (for the determination of the activity of signaling protein kinases in peripheral blood mononuclear cells; hormone concentrations: free and total testosterone, cortisol, IGF-1 and growth hormone; concentrations of alternative energy sources: ketone bodies and free fatty acids; activity of selected enzymes: lactate dehydrogenase , and creatine kinase ; gasometric indices: pH, pCO2, pO2 and electrolytes: Ca2+, Na+, K+, Cl-; concentrations of other biochemical indices: myoglobin, urea, creatinine, glucose, lactate, bilirubins ), the m. vastus lateralis ultrasound and collection of the m. vastus lateralis samples using the percutaneous muscle microbiopsy technique (for the determination of the activity of signaling protein kinases). After the resting pre-Ex procedures, the ICT will be performed. Then the post-exercise (post-Ex) blood sampling and second muscle microbiopsy will be carried out. Finally, at the end of the procedures the MVIC will be assessed.

After collection all the data, comparisons between supplementation treatment conditions (HMB vs PLA) within groups and supplementation periods, as well as comparisons between studied groups (S group vs W group) within supplementation treatment and supplementation period will be performed using T-test for independent variables. Comparisons between supplementation periods within studied groups and supplementation treatment will be performed via T-test for dependent variables. Statistical analysis will be performed using Statistica v. 13.3, StatSoft Polska Sp. z o.o., 2022.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 120
• Est. completion date: July 1, 2024
• Est. primary completion date: May 10, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 20 Years to 45 Years

Eligibility

Inclusion Criteria:

• written informed consent from all participants before the study

• a current medical clearance to practice sports,

• Group S: regular physical activity (> 250 minutes per week), training practice (> 10 years),

• Group W: a subjects characterized by certain features of the body malnutrition (BMI < 18.5), low lean body mass (FFMI < 17.4) and lack of regular physical activity that never were trained in competitive sports,

Exclusion Criteria:

• current injury,

• any health-related contraindication,

• declared general feeling of being unwell,

• unwilling to follow the study protocol,

• serious disease or metabolic problems,

• intake of ergogenic supplements 3 months before the beginning of the study,

• history of anabolic androgenic steroids or drugs use that may interfere with muscle mass control (eg, corticosteroids), or affect physical performance,

• smoking and tobacco use,

• presence of infectious disease in the previous 4 weeks of the study

Related Conditions & MeSH terms

• Aerobic Capacity
• Sport
• Sports Nutrition
• Supplementation

Intervention

Dietary Supplement:
• HMB supplementation
Group taking oral HMB free acid supplementation in a blinded liquid form.
• Placebo treatment
Group taking oral supplementation with placebo (in a blinded liquid form).

Locations

Country	Name	City	State
Czechia	Department of Physiology and Biochemisty at the Faculty of Physical Education and Sport (Charles University, Prague, Czech Republic)	Prague	Prague 6
Poland	Department of Sports Dietetics, Poznan University of Physical Education	Poznan	Wielkopolska

Sponsors (4)

Lead Sponsor	Collaborator
Poznan University of Physical Education	Faculty of Physical Education and Sport at Charles University, Czech Republic, National Science Centre, Poland, Poznan University of Life Sciences, Poland

Countries where clinical trial is conducted

Czechia,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in the molecular potential after supplementation and exercises-induced stress stimuli on the organism	AKTser473, mTORSer2448, p70S7K1Thr389, 4E-BP1Ser65/Thr70, and 4EBP1Thr37/46 kinase activity (optical density)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in the muscle cholesterol and mevalonate content (in the vastus lateralis muscle samples) after supplementation and exercises-induced stress stimuli on the organism	Muscle cholesterol and mevalonate content (units)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in blood concentrations of hormones: free and total testosterone, cortisol, IGF-1, growth hormone after supplementation and exercises-induced stress stimuli on the organism.	Blood free and total testosterone, cortisol, IGF-1, growth hormone content	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in creatine kinase (CK) and lactate dehydrogenase (LDH) activity (IU) in blood after supplementation and exercises-induced stress stimuli on the organism	CK and LDH activity (IU)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in body mass and body mass composition after supplementation and exercises-induced stress stimuli on the organism	Body mass, fat free mass, fat mass (kg)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in maximal oxygen uptake during the incremental cycling test after supplementation and exercises-induced stress stimuli on the organism	VO2max level (mL/min)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in total body water content after supplementation and exercises-induced stress stimuli on the organism	Body water content (L)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in other biochemical indices: myoglobin, urea, creatinine, glucose, lactate, bilirubins and electrolytes (Ca2+, Na+, K+, Cl-) after supplementation and exercises-induced stress stimuli on the organism	Blood concentrations of : myoglobin (mmol/L), urea (mmol/L), creatinine (mmol/L), glucose (mmol/L), lactate (mmol/L), bilirubins (mmol/L), and electrolytes [Ca2+, Na+, K+, Cl-] (mmol/L)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in utilization of energy substrates during rest and physical exercise after supplementation and exercises-induced stress stimuli on the organism	Utilization of energy substrates - fats, carbohydrate and protein during rest and exercise (g/min)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in resting and exercise energy expenditures after supplementation and exercises-induced stress stimuli on the organism	Energy expenditure during rest and exercise (kcal/min)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in total daily energy expenditures after supplementation and exercises-induced stress stimuli on the organism	Daily energy expenditure (kcal/day)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in specific exercise performance test Fight Gone Bad after supplementation and exercises-induced stress stimuli on the organism	Number of repetitions of five different exercise - sumo deadlift high-pulls, wall ball shots, box jumps, push press and rowing on an ergometer in each of three exercise rounds and total number of repetitions of all exercises of all exercise rounds (reps	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods
Secondary	Changes in the maximum voluntary isometric contraction (MVIC) after supplementation and exercises-induced muscle damage	Maximum voluntary isometric contraction (MVIC) torque (Nm)	Day 0 [Baseline (before treatment)] and after 21 days of each two supplementation periods