Bath Myorhythms Project

NCT06997315 | Not Yet Recruiting DMC

• 1 other identifier: 7560-9757
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Human Physiology is coordinated by a circadian timing system that synchronises daily cycles of light-dark, wake- sleep, activity-rest and feeding-fasting. The alignment of these behavioural patterns with underlying biological rhythms is closely linked to physiological function, with misalignment linked to chronic metabolic diseases. The vast majority of evidence about rhythms in metabolism comes from studies of rodents, which is remarkable given that rodents differ fundamentally from humans in both behaviour and metabolic regulation. Moreover, almost no research in any species has examined the effects of muscle contractile activity on 24-h rhythms in metabolism. Skeletal muscle is a key site of metabolic regulation and contractile activity is a powerful stimulus to increase metabolism. The researchers have established a novel protocol for serial muscle sampling throughout 24 hours and pilot work completed in preparation for this grant revealed diurnal transcriptomic and lipidomic rhythms in human skeletal muscle. Further development of that protocol has used enteral feeding via a tube which delivers nutrient directly to the stomach to enable constant nutrient delivery (including during sleep), with preliminary data indicating that underlying rhythms in metabolism are responsive to nutrient availability patterns. The researchers will now capitalise on those findings by incorporating multiple isotope tracers within the protocol, thus finally documenting the nature of rhythmic flux in carbohydrate metabolism and protein turnover in human skeletal muscle, and how those rhythms are aligned with timing and patterns of exercise. In summary, participants will stay in the laboratory for 36 hours with 24 hours of constant feeding via nasogastric tube, and muscle and blood sampling. Participants will be allocated to either the early or late exercise group (involving 1 hour of cycling at either 0800 or 2000 h, respectively) or the control group who will rest for the 24 hours.

Conditions

Metabolic Regulation

Outcome Measures

Primary Outcomes (5)

• Carbohydrate flux

  Rates of exogenous glucose appearance, endogenous glucose production, total carbohydrate oxidation, exogenous carbohydrate oxidation and net glycogen degradation in muscle biopsies over 24 hours

  24 hours

• Skeletal muscle protein synthesis

  Plasma amino acid concentrations derived from the L-\[ring-13C\]-phenylalanine infusion over 24 hours.

  24 hours

• Skeletal muscle protein synthesis

  Protein fractional synthetic rates in muscle samples derived from the L-\[ring-13C\]-phenylalanine infusion over 24 hours.

  24 hours

• Mass spectrometry phosphoproteomics

  Mass spectrometry phosphoproteomics from skeletal muscle biopsies over 24 hours.

  24 hours

• Protein content of proteins involved in insulin signalling, glucose transport and protein synthesis.

  The content of proteins involved in insulin signalling, glucose transport and protein synthesis determined by semi-quantitative western blotting in skeletal muscle biopsies over 24 hours.

  24 hours.

Secondary Outcomes (17)

• Skeletal muscle gene expression

  24 hours

• Intramuscular metabolites

  24 hours

• Intramuscular enzymes

  24 hours

• Plasma glucose concentrations

  24 hours

• Plasma non-esterified fatty acid concentrations

  24 hours

Other Outcomes (9)

• Skeletal muscle lipid concentrations

  24 hours

• Blood cell counts

  24 hours

• Skeletal muscle autophagic flux

  24 hours

Study Arms (3)

Control

ACTIVE COMPARATOR

Other: No exercise

Early exercise

EXPERIMENTAL

Other: Time of exercise

Late exercise

EXPERIMENTAL

Other: Time of exercise

Interventions

Time of exercise OTHER

The intervention is 1 hour of exercise at 50% between lactate threshold 1 and 2 either in the morning or the evening at the start of the 24 hour sampling period.

Early exercise; Late exercise

No exercise OTHER

The participants will rest for the full 24 hour sampling period.

Control

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Women and men - with targeted recruitment to encourage females to volunteer given previous recruitment rates; anticipating fewer women than men, sex will also be included as a strata in the randomisation plan to favour the few who do volunteer being relatively evenly distributed between conditions.
• A body mass index of \>18 and \<35 kg•m-2.
• Minimum absolute body mass of 67 kg (to accommodate the required dose of lidocaine for 7 biopsies, plus additional for pre-incisions)
• be between 18-50 years of age
• Premenopausal women
• Metabolically healthy (free from diagnosed metabolic illness or family history of type II diabetes
• be able and willing to give informed oral and written consent,
• complete and meet the defined criteria of pre-study questionnaires and screens
• have a regular sleep cycle with a sleep duration between 6 and 8 h
• do not exhibit extreme morning or evening preference (Horne and Ostberg, 1976)
• agree to keep a constant sleep/wake cycle with a self-selected 8-h duration in bed/dark trying to sleep (from which it cannot be deviated by more than 30 minutes) for one week prior to the lab study
• obtain 15 minutes of sunlight within 1.5 hours of waking up and agree to nap only within a 4 h designated nap window for one week prior to the lab study
• allow confirmation of compliance to these instructions by wearing ActiHeart and light monitors continuously and complete daily sleep and event diaries for one week before the study session
• agree to refrain from alcohol, caffeine, strenuous exercise and certain food components for one day before the study session
• agree to weigh and record daily meals (based on individual energy requirements) for TWO days prior to the study

You may not qualify if:

• are taking regular medication (also non-prescribed) or food supplements (e.g. vitamins, minerals, fish oil, antioxidant tablets) from which it is not possible to refrain, known to influence: sleep/alertness/the circadian timing system (e.g. beta-blockers, barbituates, antidepressants, benzodiazepines, melatonin, ritalin, modafinil, soporifics, St John's Wort), any of the metabolic functions (e.g. affecting thyroid, kidney, liver or gastrointestinal function) any of the inflammatory markers (e.g. aspirin, ibuprofen, antibiotics, hay fever medication, medication for sore throats and colds), and/or any of the endothelial markers (e.g. ACE inhibitors and angiotensin (receptor) blockers, diuretics, beta-blockers, anti-thrombosis medication), any anticoagulant medication
• have a history of psychiatric or neurological disease or drug and alcohol abuse
• have donated over 400 ml of blood in the three months preceding the study
• have participated in shift work (regularly working past a typical bed time of 2300 h) or have travelled across more than two time zones within three weeks before the study
• do not keep a regular sleep-wake cycle
• do not refrain from alcohol, caffeine containing drinks (e.g. coffee, coke, tea, Red Bull), strenuous exercise and certain foods (e.g. those high in fat and green vegetables) for one day before and during the laboratory session
• regularly consume more than 4 cups of caffeinated beverages (e.g. tea, coffee, cola) daily
• smokers
• have a known lidocaine allergy

Sponsors & Collaborators

• University of Bath: lead
• University of Surrey: collaborator
• Maastricht University: collaborator
• University of Copenhagen: collaborator
• University of Nottingham: collaborator
• Australian Catholic University: collaborator
• University of Geneva, Switzerland: collaborator

Study Sites (1)

University of Bath

Bath, BA2 7AY, United Kingdom

Location

Central Study Contacts

James A Betts, PhD

CONTACT

01225 383 448; jb335@bath.ac.uk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 22, 2025
• First Posted: May 30, 2025
• Study Start: May 23, 2025
• Primary Completion (Estimated): November 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share

Locations

GB (1)