Skeletal Muscle Adaptations to Peptide-Supplemented Resistance Exercise Training

NCT07773142 | Recruiting

• 1 other identifier: RG_26-018
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

Brief Summary

Skeletal muscle size, an important metabolic tissue, is governed by the balance between two opposing processes, muscle protein synthesis and muscle protein breakdown. In response to long-term resistance exercise (weightlifting), skeletal muscle growth is commonly observed and it is believed that this is due to increases in muscle protein synthesis which leads to a positive net protein balance stimulating muscle growth. Due to its links to overall metabolic health, maximising muscle growth in response to resistance exercise training has become a significant focus in recent times, with various dietary supplements proposed due to their additive effects on muscle growth with resistance training. Protein supplementation, most commonly whey protein, is the most popular dietary supplement utilised by individuals completing resistance exercise training, however, more recent research has suggested that specific components of whey protein, as well as other foodstuffs, have the potential to individually activate growth pathways within skeletal muscle. This study will investigate whether daily supplementation with a combination of these compounds is able to produce greater muscle growth, compared to a placebo, when combined with resistance exercise training. We will also investigate whether this supplement can also produce greater increase in strength as well as studying the potential mechanisms behind any of these preferential adaptations in muscle samples which will be collected before and after the training period.

Conditions

Supplement; Resistance Training Adaptation

Keywords

skeletal muscle; hypertrophy; autophagy; resistance exercise; resistance training; supplementation

Outcome Measures

Primary Outcomes (4)

• Leg Press 1RM strength

  Maximal strength completed on a 45 degree incline, weight plate-loaded leg press machine (statistically powered primary outcome)

  From enrolment to the final testing visit of the participant (~5 days following final testing session)

• 1RM strength for seated chest press, standing overhead press, bent-over row, 45-degree leg press, knee extension, seated hamstring curl, and standing calf press

  Maximal Strength on all other exercises completed in training sessions throughout intervention

  From enrolment to the final testing visit of the participant (~5 days following final testing session)

• Leg extensor MVC

  Maximal force production in a isometric knee extension movement using a dynamometer

  From enrolment to the final testing visit of the participant (~5 days following final testing session)

• Muscle growth/hypertrophy

  Assessments of muscle growth/hypertrophy through macro- and micro-scopic assessments: * B-mode ultrasound assessments of vastus lateralis cross-sectional area and thickness * Immunofluorescence microscopy to assess fibre-type specific changes in fibre cross-sectional area

  From enrolment to the final testing visit of the participant (~5 days following final testing session) for ultrasound assessments. Muscle samples will be analysed for fibre CSA from end of final participant testing until end of study date.

Secondary Outcomes (5)

• Body Composition

  From enrolment to the final testing visit of the participant (~5 days following final testing session)

• Skeletal muscle autophagic flux

  Skeletal muscle samples will be analysed from the final participant session until the study end date.

• Lysosome and autophagy-related protein content

  Skeletal muscle samples will be analysed from the final participant session until the study end date.

• Autophagic and anabolic signalling processes (phosphorylation events, translocation, colocalization)

  Skeletal muscle samples will be analysed from the final participant session until the study end date.

• Satellite Cell Content

  Skeletal muscle samples will be analysed from the final participant session until the study end date.

Study Arms (2)

Supplement

ACTIVE COMPARATOR

The supplement will comprise 5 active ingredients: 1) Dileucine (Peptide 185™, 2g/serving), comprising two chemically bonded leucine amino acid molecules which are commonly found within animal protein sources, 2) PeptiStrong®( 2.4g/serving), a trademarked hydrolysed Broad Bean (Vicia faba) protein extract, 3) Calcium β-hydroxy-β-methylbutyrate monohydrate (myHMB®, 1.5g/serving), a leucine metabolite in its calcium salt form, 4) Creatine monohydrate (5g/serving), a well-researched dietary supplement which increases muscle strength and power by improving cellular energy availability, and 5) PepForm® creatine monohydrate (1g/serving), a trademarked creatine monohydrate product which is purported to enhance creatine bioavailability by binding creatine with peptides derived from whey protein. The supplement will be consumed daily throughout the 8-week training period - in the morning on non-training days and within 30 minutes of completing training session on training days.

Other: Resistance Exercise Training with or without daily supplementation; Radiation: Dual Energy X-Ray Absorptiometry (DEXA) Scan; Procedure: Muscle Sampling; Procedure: Blood Sampling; Other: Leg Extensor MVC Test; Other: 1 repetition maximum tests; Procedure: Ultrasound VL Muscle Thickness/Cross-sectional Area Measurement; Other: 3-day weighed food diary; Dietary Supplement: Daily Supplementation with active or placebo comparator

Placebo

PLACEBO COMPARATOR

The placebo will contain 12g maltodextrin per serving and is taste and colour matched to the active comparator. The placebo will be consumed daily throughout the 8-week training period - in the morning on non-training days and within 30 minutes of completing training session on training days.

Other: Resistance Exercise Training with or without daily supplementation; Radiation: Dual Energy X-Ray Absorptiometry (DEXA) Scan; Procedure: Muscle Sampling; Procedure: Blood Sampling; Other: Leg Extensor MVC Test; Other: 1 repetition maximum tests; Procedure: Ultrasound VL Muscle Thickness/Cross-sectional Area Measurement; Other: 3-day weighed food diary; Dietary Supplement: Daily Supplementation with active or placebo comparator

Interventions

Resistance Exercise Training with or without daily supplementation OTHER

The intervention involves undertaking 3 supervised, in person, training sessions per week for 8 weeks, which are designed to increase muscle mass and strength of all major muscle groups. Each session will involve performing 7 different exercises in the order of a seated chest press, standing overhead press, bent-over row, 45-degree leg press, knee extension, seated hamstring curl, and a seated calf press. For each exercise, participants perform 4 working sets to volitional failure with 75% 1RM with a two-minute rest period will be given between sets. Resistance exercise loads will be adjusted between sets to ensure that participants consistently reach volitional failure between 8-12 repetitions and reset during week 5 when interim 1RM tests are undertaken. Throughout this period, participant will consume their assigned supplement daily either in the morning on non-training days or within 30 mins of training on training days.

Placebo; Supplement

Dual Energy X-Ray Absorptiometry (DEXA) Scan RADIATION

Participant's body composition will be determined through a full body DEXA scan before and after the intervention. They will have their height and weight determined prior to this scan to confirm their BMI and to calibrate the DEXA machine. The DEXA scan involves resting supine for approximately 20 minutes whilst the machine utilises a low dose of ionising radiation to estimate the total amount of fat mass and fat-free (lean) mass. The distribution of these is also determined across different body segments. The dosage of radiation is approximately 10 micro-Sieverts (µSv), which is far lower than the 80µSv airline passengers are typically exposed to during a single transatlantic flight. Scans will be conducted in line with IRMER regulations/guidelines by an appropriately trained individual.

Placebo; Supplement

Muscle Sampling PROCEDURE

Before and after the 8-week training intervention, a skeletal muscle (vastus lateralis) biopsy sample will be obtained from participants. This will be completed by a trained individual, in sterile conditions and under local anaesthetic using the Bergstrom needle technique modified for suction. These will be immediately processed and stored for subsequent analysis following intervention completion by all participants.

Placebo; Supplement

Blood Sampling PROCEDURE

Before and after the 8 week training intervention, a single 10ml venous blood sample will be collected from participant's antecubital vein. Serum and plasma will be subsequently isolated from the sample and stored for future analysis.

Placebo; Supplement

Leg Extensor MVC Test OTHER

This uses an isokinetic dynamometer to determine the peak amount of force that the leg extensor (thigh) muscles can produce during a voluntary muscle contraction. Participants will be required to sit on a padded dynameter chair with their lower legs naturally hanging over the edge of the chair, bent at a 90-degree angle. On each attempt, participants will be asked to cross their arms over their upper body and, following a count of 3 seconds, to kick as hard and as fast as possible into the stationary shin pad for 5 seconds, with peak force recorded during each attempt. This will be completed before and after the 8 week training/supplement intervention.

Placebo; Supplement

1 repetition maximum tests OTHER

Participants will next complete 1RM strength tests for 7 different resistance exercises before, mid-way and after the intervention. Each exercise will target different areas of the body and will be performed throughout the 8-week training programme. These include a seated chest press, standing overhead press, bent-over row, 45-degree leg press, knee extension, seated hamstring curl, and seated calf press. This involves lifting progressively increasing loads for each exercise until a single repetition can no longer be completed with correct form. Attempts will be separated by a rest interval of 2 minutes.

Placebo; Supplement

Ultrasound VL Muscle Thickness/Cross-sectional Area Measurement PROCEDURE

Participants will have their vastus lateralis muscle thickness and cross-sectional area measured via an Ultrasound scan. They will be asked to lie still on a medical examination couch whilst a member of the research team locates the position of their greater trochanter and lateral condyle of the femur. The ultrasound probe will then be placed on this mark and repositioned vertically to identify the medial and lateral borders of the VL. The midpoint of these locations will be marked and the distance between the superficial and deep aponeuroses of the VL muscle will be measured to quantify VL muscle thickness. A wide-view image spanning the entire cross-section of the vastus lateralis will also be obtained for cross-sectional area assessment.

Placebo; Supplement

3-day weighed food diary OTHER

Participants will be asked to record a 3-day weighted food diary on weeks 1, 5 and 8 of the resistance training programme. The choice of days will be at the participants discretion but must include 2 weekdays and 1 weekend day to account for dietary variation throughout the week. On these days, they will be required to record all food and drink consumed which contains calories, including the weight/volume and branding. Food diaries will be analysed for macronutrient and caloric intake. This data will be used to determine whether participant's diets, especially protein intake, remains relatively stable throughout the interventional period. Full instructions on how to properly record a weighted food diary will be provided by the research team at the start of the training period. Depending on participant preference, diaries may be recorded physically within a provided logbook or electronically using a mobile application (MyFitnessPal). Weighing scales will be provided by the research team

Placebo; Supplement

Daily Supplementation with active or placebo comparator DIETARY_SUPPLEMENT

In a double-blind manner, participants will be randomised to supplement or placebo cohorts. Assigned supplements will be consumed daily across the 8-week intervention either in the morning on non-training days or with 30 minutes of training on training days. The placebo will contain maltodextrin carbohydrate, whereas the supplement will comprise 5 active ingredients: 1) Dileucine (Peptide 185™, 2g/serving), 2) PeptiStrong®( 2.4g/serving), a trademarked hydrolysed Broad Bean (Vicia faba) protein extract, 3) Calcium β-hydroxy-β-methylbutyrate monohydrate (myHMB®, 1.5g/serving), a leucine metabolite in its calcium salt form, 4) Creatine monohydrate (5g/serving), , and 5) PepForm® creatine monohydrate (1g/serving), a trademarked creatine monohydrate product where creatine is bound to peptides derived from whey proteins. Supplements will be provided in opaque contained withs instructions to add one scoop (provided) of supplement/placebo to 300ml water.

Placebo; Supplement

Eligibility Criteria

• Age: 18 Years - 35 Years
• Gender Eligibility Details: Cis-gender males and females
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Aged 18-35 years
• Body Mass Index (BMI, calculated by research team based on height and weight) between 18.5-27.4 kg.m-2
• Meeting UK physical activity guidelines (150 mins moderate or 75 mins vigorous activity/week)
• Not currently participating in structured progressive resistance exercise training or have regularly participated in previous 6 months
• In good health, being free from disease or conditions (e.g., Type-II diabetes, hyper/hypothyroidism, irritable bowel syndrome, polycystic ovary syndrome) which influence skeletal muscle metabolism or digestion (self-declared)

You may not qualify if:

• Have an allergy to ingredients of the supplement or placebo supplement (e.g., legume/bean, corn allergies)
• Have used dietary supplements which are known to affect skeletal muscle recovery and exercise adaptations (e.g., creatine) within the previous month
• Are a smoker/vaper or have a history of smoking/vaping in previous year
• Have a respiratory condition (e.g., asthma, chronic obstructive pulmonary disease)
• Using hormone therapy (not including birth control), anabolic steroids, or recreational drugs
• Are pregnant or currently breastfeeding
• Are currently trying to conceive a child
• Have any injury or body weakness which prevents participation in full body resistance exercise
• Have a known allergy to lidocaine

Sponsors & Collaborators

• University of Birmingham: lead

Study Sites (1)

School of Sport, Exercise and Rehabilitation Sciences, University of Birmingham

Birmingham, Birmingham, B15 2TT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Hypertrophy

Interventions

Absorptiometry, Photon; Blood Specimen Collection; Exercise

Condition Hierarchy (Ancestors)

Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Radiography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Densitometry; Photometry; Chemistry Techniques, Analytical; Investigative Techniques; Specimen Handling; Clinical Laboratory Techniques; Punctures; Surgical Procedures, Operative; Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Study Officials

• Nathan Hodson

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Nathan Hodson, PhD

CONTACT

07526146514; n.w.hodson@bham.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Parallel-arm, randomised, double-blind placebo controlled trial

Study Record Dates

• First Submitted: August 14, 2026
• First Posted: August 19, 2026
• Study Start: July 14, 2026
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: August 21, 2026

Record last verified: 2026-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: IPD will be available upon request following publication of the IPD with no end date
• Access Criteria: Qualified researchers with an approved scientifically sound research proposal from recognized academic, clinical, or commercial institutions can request IPD from the principal investigator. In such cases, the de-identified data long with the study protocol will be provided via a secure cloud-based research environment.

Locations

GB (1)