Circadian RhythmsNCT03906409
Effect of Nutrient Delivery Pattern on Biological Rhythms in Human Skeletal Muscle
A study testing Constant and Bolus in people with Circadian Rhythms and Feeding Patterns, run by University of Bath at 1 site in United Kingdom.
Trial summary
Recent work has established biological rhythms in human skeletal muscle. It remains unknown how the timing and pattern of meals influences these rhythms. Therefore, this study sets out to establish how frequent (CONSTANT) vs infrequent (BOLUS) feeding patterns influence established biological rhythms in skeletal… Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Circadian Rhythms, Feeding Patterns
- What is being tested?
- Constant and Bolus
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 28 Feb 2019to 28 Feb 2022
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Body mass index >19 but <30 kg/m2
- 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 hours, 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 hour sleep duration (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 monitors continuously and complete daily sleep and event diaries for one week before the study session,
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- Agree to refrain from alcohol, caffeine, heavy exercise and certain food components TWO days before the study session,
- Agree to weigh and record daily meals (based on individual energy requirements) for TWO days prior to the study,
- Agree to refrain from prescribed and 'over the counter' medication and food/vitamin supplements for a wash-out period three weeks before and during the study.
Who cannot join
- 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, antiobiotics, 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),
- Have a history of any circadian or sleep disorder or metabolic, cardiovascular or chronic infectious / inflammatory disease as confirmed by the GP or the pre-study questionnaires (e.g. a Pittsburgh Sleep Quality Index > 5 will result in exclusion),
- 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,
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- Have participated in shift work or have travelled across more than two time zones within three weeks of the study,
- Do not keep a regular sleep-wake cycle,
- Do not refrain from alcohol, caffeine containing drinks (e.g. coffee, coke, tea, redbull), heavy exercise and certain foods (e.g. those high in fat and green vegetables) TWO days before and during the laboratory session,
- Normally consume more than 4 cups of caffeinated beverages (e.g. tea, coffee, cola) daily
- Smokers
Trial locations and contacts
1 site in 1 country.
About this study
Recent work has established biological rhythms in human skeletal muscle. It remains unknown how the timing and pattern of meals influences these rhythms. Therefore, this study sets out to establish how frequent (CONSTANT) vs infrequent (BOLUS) feeding patterns influence established biological rhythms in skeletal muscle.
Read the detailed description
Human metabolism is regulated on a daily basis via a circadian timing system that coordinates metabolic responses between various tissues. Skeletal muscle is a major site for the oxidation or storage of key metabolites, with recent studies at Bath and Surrey demonstrating biological rhythms in this tissue over a 24-h cycle. It is well established that dysregulated metabolism in skeletal muscle contributes to poor metabolic health and that poor diet is a causal factor in this deterioration. Diet can be characterised by three nutritional considerations: how much is eaten (i.e. quantity/dose), what is eaten (i.e. type) and when it is eaten (i.e. timing). Whilst most dietary approaches and most scientific studies have focused on the first two factors, there is convincing evidence that human health is also dictated by the pattern of nutrient delivery; this includes the frequency and regularity of daily eating occasions, along with their timing both in absolute terms (i.e. time-of-day) and relative to when other inter-related daily events occur - or usually occur (e.g. light exposure, sleep, exercise, etc.).
It remains unknown whether the interaction of such factors may affect the biological rhythms previously documented in human skeletal muscle. In particular, from a basic science perspective, the fundamental contrast between frequent versus infrequent feeding warrants investigation. To this end, 16-24 healthy adults will be randomly allocated to receive their individual daily energy requirements delivered via naso-gastric infusion either continuously over 24 hours (n=8-12; CONSTANT) or as two bolus infusions at the start (0800 h) and mid-point (2000 h) of the monitoring period (n=8-12; BOLUS). Serial skeletal muscle (vastus lateralis) biopsies will be sampled every 4 hours over a controlled 24-h sleep-wake cycle.
- Conditions
- Circadian Rhythms, Feeding Patterns
- Being tested
- Constant, Bolus
- Keywords
- Feeding Patterns, Skeletal Muscle, Metabolism, Circadian Rhythms, Diurnal Rhythms
- Medical subject headings
- Feeding Behavior
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ConstantOther
Participants will be provided with their daily energy requirements in a continuous drip across the day (1 ml/minute).
BolusOther
Participants will be provided with their daily energy requirements in two bolus feeds. One at 08:00-08:15 and one at 20:00-20:15
| Study group | Role | What they receive |
|---|---|---|
| Constant | Active comparator | Participants will be provided with their daily energy requirements in a continuous drip across the day (1 ml/minute). Receives: Other: Constant |
| Bolus | Experimental | Participants will be provided with their daily energy requirements in two bolus feeds. One at 08:00-08:15 and one at 20:00-20:15 Receives: Other: Bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Autophagy
Rhythms in autophagy with different feeding patterns
Measured: 4 hours
Transcriptomic, rhythms in human skeletal muscle
Assessing rhythms in core-clock genes within the muscle samples
Measured: Over a 24-hour period at a 4 hour resolution
Secondary outcomes (2)
Endocrine responses of systemic blood plasma over 24-hours
Rhythms in endocrine regulation of metabolism over a 24-hour period (e.g. insulin, appetite hormones)
Measured: 24-hours
Continuously monitored subcutaneous interstitial glucose concentrations
Assessed using a continual glucose monitor
Measured: 48-hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start28 Feb 2019
- Primary completion28 Feb 2022
- Study completion28 Feb 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Circadian RhythmsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomised to one of two parallel trial arms: constant feed or bolus feed
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Bath
- Sponsor type
- University, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Responsible party
- Principal investigator, James Betts, University of Bath
- Investigators
- Harry A Smith, MSci, Principal investigator, University of BathJames A Betts, PhD, Principal investigator, University of Bath
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03906409
- Sponsor's protocol ID
- FE
- Status last verified
- Apr 2023
- First submitted
- 4 Apr 2019
- Last updated
- 14 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Christou S, Wehrens SMT, Isherwood C, Moller-Levet CS, Wu H, Revell VL, Bucca G, Skene DJ, Laing EE, Archer SN, Johnston JD. Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis. Sci Rep. 2019 Feb 25;9(1):2641. doi: 10.1038/s41598-019-39668-3.
PubMed 30804433Perrin L, Loizides-Mangold U, Chanon S, Gobet C, Hulo N, Isenegger L, Weger BD, Migliavacca E, Charpagne A, Betts JA, Walhin JP, Templeman I, Stokes K, Thompson D, Tsintzas K, Robert M, Howald C, Riezman H, Feige JN, Karagounis LG, Johnston JD, Dermitzakis ET, Gachon F, Lefai E, Dibner C. Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle. Elife. 2018 Apr 16;7:e34114. doi: 10.7554/eLife.34114.
PubMed 29658882
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Nutrient Delivery Pattern on Biological Rhythms in Human Skeletal Muscle
- ClinicalTrials.gov ID
- NCT03906409
- Acronym / sponsor ID
- FE
- Conditions
- Circadian Rhythms, Feeding Patterns
- Keywords
- Feeding Patterns, Skeletal Muscle, Metabolism, Circadian Rhythms, Diurnal Rhythms
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- University of BathUniversity, hospital or other
- Collaborators
- Société des Produits Nestlé (SPN)
- Study start
- 28 Feb 2019 (actual)
- Primary completion
- 28 Feb 2022 (actual)
- Study completion
- 28 Feb 2022 (actual)
- First posted
- 8 Apr 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent work has established biological rhythms in human skeletal muscle. It remains unknown how the timing and pattern of meals influences these rhythms. Therefore, this study sets out to establish how frequent (CONSTANT) vs infrequent (BOLUS) feeding patterns influence established biological rhythms in skeletal muscle.
Detailed description
Human metabolism is regulated on a daily basis via a circadian timing system that coordinates metabolic responses between various tissues. Skeletal muscle is a major site for the oxidation or storage of key metabolites, with recent studies at Bath and Surrey demonstrating biological rhythms in this tissue over a 24-h cycle. It is well established that dysregulated metabolism in skeletal muscle contributes to poor metabolic health and that poor diet is a causal factor in this deterioration. Diet can be characterised by three nutritional considerations: how much is eaten (i.e. quantity/dose), what is eaten (i.e. type) and when it is eaten (i.e. timing). Whilst most dietary approaches and most scientific studies have focused on the first two factors, there is convincing evidence that human health is also dictated by the pattern of nutrient delivery; this includes the frequency and regularity of daily eating occasions, along with their timing both in absolute terms (i.e. time-of-day) and relative to when other inter-related daily events occur - or usually occur (e.g. light exposure, sleep, exercise, etc.).
It remains unknown whether the interaction of such factors may affect the biological rhythms previously documented in human skeletal muscle. In particular, from a basic science perspective, the fundamental contrast between frequent versus infrequent feeding warrants investigation. To this end, 16-24 healthy adults will be randomly allocated to receive their individual daily energy requirements delivered via naso-gastric infusion either continuously over 24 hours (n=8-12; CONSTANT) or as two bolus infusions at the start (0800 h) and mid-point (2000 h) of the monitoring period (n=8-12; BOLUS). Serial skeletal muscle (vastus lateralis) biopsies will be sampled every 4 hours over a controlled 24-h sleep-wake cycle.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Participants will be randomised to one of two parallel trial arms: constant feed or bolus feed
| Arm | Type | Receives |
|---|---|---|
| Constant | Active comparator | Other: ConstantParticipants will be provided with their daily energy requirements in a continuous drip across the day (1 ml/minute). |
| Bolus | Experimental | Other: BolusParticipants will be provided with their daily energy requirements in two bolus feeds. One at 08:00-08:15 and one at 20:00-20:15 |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- Body mass index >19 but <30 kg/m2
- 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 hours, 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 hour sleep duration (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,
Key exclusion criteria (11 listed)
- 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, antiobiotics, 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),
- Have a history of any circadian or sleep disorder or metabolic, cardiovascular or chronic infectious / inflammatory disease as confirmed by the GP or the pre-study questionnaires (e.g. a Pittsburgh Sleep Quality Index > 5 will result in exclusion),
- Have a history of psychiatric or neurological disease or drug and alcohol abuse,
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ConstantParticipants will be provided with their daily energy requirements in a continuous drip across the day (1 ml/minute). | Other | Constant |
| BolusParticipants will be provided with their daily energy requirements in two bolus feeds. One at 08:00-08:15 and one at 20:00-20:15 | Other | Bolus |
Primary outcome
Autophagy
Time frame: 4 hours
Rhythms in autophagy with different feeding patterns
Transcriptomic, rhythms in human skeletal muscle
Time frame: Over a 24-hour period at a 4 hour resolution
Assessing rhythms in core-clock genes within the muscle samples
2 secondary outcomes
Endocrine responses of systemic blood plasma over 24-hours
Time frame: 24-hours
Continuously monitored subcutaneous interstitial glucose concentrations
Time frame: 48-hours
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2023.
- Background: PubMed 30804433Christou S, Wehrens SMT, Isherwood C, Moller-Levet CS, Wu H, Revell VL, Bucca G, Skene DJ, Laing EE, Archer SN, Johnston JD. Circadian regulation in human white adipose tissue revealed by transcriptome and metabolic network analysis. Sci Rep. 2019 Feb 25;9(1):2641. doi: 10.1038/s41598-019-39668-3.
- Background: PubMed 29658882Perrin L, Loizides-Mangold U, Chanon S, Gobet C, Hulo N, Isenegger L, Weger BD, Migliavacca E, Charpagne A, Betts JA, Walhin JP, Templeman I, Stokes K, Thompson D, Tsintzas K, Robert M, Howald C, Riezman H, Feige JN, Karagounis LG, Johnston JD, Dermitzakis ET, Gachon F, Lefai E, Dibner C. Transcriptomic analyses reveal rhythmic and CLOCK-driven pathways in human skeletal muscle. Elife. 2018 Apr 16;7:e34114. doi: 10.7554/eLife.34114.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Harry A Smith, MSci principal investigator
University of Bath
James A Betts, PhD principal investigator
University of Bath
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Constant and Bolus in people with Circadian Rhythms and Feeding Patterns, run by University of Bath at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Autophagy (time frame: 4 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03906409, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2023.