Protein and Skeletal Muscle in Older Twins: Role of the Gut Microbiome

NCT ID: NCT04309292

Last Updated: 2022-10-27

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

71 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-04-29

Study Completion Date

2021-12-20

Brief Summary

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Research Question: Does the gut microbiome contribute to muscle anabolic resistance to protein supplementation in older adults?

Background: Loss of muscle occurs with age and skeletal muscle in older adults can display anabolic resistance to protein in diet. It has been hypothesised that the gut microbiome may play a role in this relationship and therefore could be targeted.

Aim:

This trial aims to test whether modulation of the gut microbiome, in addition to protein supplementation, can improve skeletal muscle function versus protein supplementation alone.

Methods:

Double blinded, randomised, placebo controlled, dietary intervention study. Twin pairs will be randomised to either receive protein supplementation plus placebo or protein supplementation plus a gut microbiome modulator (prebiotic plus probiotic) for 12 weeks. Primary outcome will be muscle function measured using chair-rise time.

Conclusion:

Anabolic resistance warrants further characterisation to guide future therapeutic interventions, especially considering its role in the development of disability, sarcopenia and frailty.

Detailed Description

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Research Question: Does the gut microbiome contribute to muscle anabolic resistance to protein supplementation in older adults?

Background: Loss of skeletal muscle mass and strength occurs with increasing age and is associated with loss of function, disability, and the development of sarcopenia and frailty. Dietary protein is essential for skeletal muscle function, but older adults do not respond as well as younger people to protein, so called 'anabolic resistance'. The aetiology and molecular mechanisms for this are not understood, however a number have been proposed. The gut microbiome is known to play a key role in a number of these postulated mechanisms. This has led us to hypothesise that the gut microbiome may mediate anabolic resistance and could represent an exciting new target for ameliorating muscle loss in older adults.

Aim:

This trial aims to test whether modulation of the gut microbiome, in addition to protein supplementation, can improve skeletal muscle function versus protein supplementation alone.

Methods:

Double blinded, randomised, placebo controlled, dietary intervention study. Volunteers will be recruited in twin pairs from TwinsUK cohort, for which extensive baseline data are available. The twin nature of the study allows for close genetic and environmental matching at baseline. Each pair will be randomised to either receive protein supplementation plus placebo or protein supplementation plus a gut microbiome modulator (prebiotic plus probiotic). Intervention period will be 12 weeks. Clinical and biochemical measures will be taken at 0, and 12 weeks, with 2-monthly contact. Gut microbiota composition will be measured, alongside a battery of physical assessments. Primary outcome will be muscle function measured using chair-rise time. The trial will be delivered remotely using video calls, and postal boxes.

Conclusion:

Anabolic resistance warrants further characterisation to guide future therapeutic interventions, especially considering its role in the development of disability, sarcopenia and frailty. Therapeutic options are badly needed, particularly for older adults who cannot undertake exercise programmes.

Conditions

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Sarcopenia Frailty Age-Related Sarcopenia

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Treatment Arm

protein supplementation plus prebiotic supplementation

Group Type EXPERIMENTAL

Prebiotic food supplement

Intervention Type DIETARY_SUPPLEMENT

Darmocare Pre = trade name Gut microbiome modulator

Protein supplement

Intervention Type DIETARY_SUPPLEMENT

commercially available protein supplementation with high leucine content

Placebo Arm

Protein supplementation plus placebo

Group Type PLACEBO_COMPARATOR

Protein supplement

Intervention Type DIETARY_SUPPLEMENT

commercially available protein supplementation with high leucine content

Maltrodextrin (placebo)

Intervention Type DIETARY_SUPPLEMENT

Starchy substance

Interventions

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Prebiotic food supplement

Darmocare Pre = trade name Gut microbiome modulator

Intervention Type DIETARY_SUPPLEMENT

Protein supplement

commercially available protein supplementation with high leucine content

Intervention Type DIETARY_SUPPLEMENT

Maltrodextrin (placebo)

Starchy substance

Intervention Type DIETARY_SUPPLEMENT

Eligibility Criteria

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Inclusion Criteria

* Aged \>=60 years
* Dietary protein intake of \<1.3g/kg/day
* Able to consent
* Able to access video calls on a device such as laptop/tablet

Exclusion Criteria

* Severe food allergy
* Current or recent antibiotic use (preceding 3 months)
* Currently or recent use of protein or leucine supplements (preceding 3 months)
* Currently or recent use of probiotic or prebiotic food supplements (preceding 3 months)
* Current or prior history of gastrointestinal disease e.g. gastrointestinal cancer, inflammatory bowel disease, bariatric surgery, irritable bowel syndrome
* history of any significant injury or surgery which currently affects physical functioning and ability to undertake chair stand test
* weight loss of ≥5% of body weight in preceding 6-12 months
* Currently involved in other intervention studies
* Any condition or circumstance likely to interfere with the normal conduct of the study and interpretation of the results, as judged by the investigators As the study population are over 60 years old, it is assumed that there will be no pregnant women who are eligible to take part.
Minimum Eligible Age

60 Years

Maximum Eligible Age

120 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role collaborator

King's College London

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Claire Steves

Role: PRINCIPAL_INVESTIGATOR

The Department of Twin Research & Genetic Epidemiology

Locations

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Department of Twin Research and Genetics

London, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Ni Lochlainn M, Bowyer RCE, Steves CJ. Dietary Protein and Muscle in Aging People: The Potential Role of the Gut Microbiome. Nutrients. 2018 Jul 20;10(7):929. doi: 10.3390/nu10070929.

Reference Type BACKGROUND
PMID: 30036990 (View on PubMed)

Ni Lochlainn M, Bowyer RCE, Moll JM, Garcia MP, Wadge S, Baleanu AF, Nessa A, Sheedy A, Akdag G, Hart D, Raffaele G, Seed PT, Murphy C, Harridge SDR, Welch AA, Greig C, Whelan K, Steves CJ. Effect of gut microbiome modulation on muscle function and cognition: the PROMOTe randomised controlled trial. Nat Commun. 2024 Feb 29;15(1):1859. doi: 10.1038/s41467-024-46116-y.

Reference Type DERIVED
PMID: 38424099 (View on PubMed)

Ni Lochlainn M, Nessa A, Sheedy A, Horsfall R, Garcia MP, Hart D, Akdag G, Yarand D, Wadge S, Baleanu AF, Whelan K, Steves C. The PROMOTe study: targeting the gut microbiome with prebiotics to overcome age-related anabolic resistance: protocol for a double-blinded, randomised, placebo-controlled trial. BMC Geriatr. 2021 Jul 1;21(1):407. doi: 10.1186/s12877-021-02301-y.

Reference Type DERIVED
PMID: 34210274 (View on PubMed)

Other Identifiers

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1234

Identifier Type: -

Identifier Source: org_study_id

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