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

October 26, 2022 updated by: King's College London

Dietary Protein and Skeletal Muscle in Older Twins - Targeting the Gut Microbiome to Overcome Anabolic Resistance: The PROMOTe Study

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.

Study Overview

Detailed Description

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.

Study Type

Interventional

Enrollment (Actual)

71

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • London, United Kingdom
        • Department of Twin Research and Genetics

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

60 years to 120 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Treatment Arm
protein supplementation plus prebiotic supplementation
Darmocare Pre = trade name Gut microbiome modulator
commercially available protein supplementation with high leucine content
PLACEBO_COMPARATOR: Placebo Arm
Protein supplementation plus placebo
commercially available protein supplementation with high leucine content
Starchy substance

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in chair rise time
Time Frame: baseline and end of study (12 weeks)
Chair rise time refers to the time it takes to complete 5 chair rises, without using arms. It is a well-recognised proxy marker of muscle strength. The change from baseline chair rise time at 12 weeks is the primary outcome. The residuals of change will be used in analysis.
baseline and end of study (12 weeks)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Gripstrength, as measured by dynamometer
Time Frame: baseline and end of study (12 weeks)
A marker of muscle strength, measured in kilograms. Dominant hand will be used. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Microbiome composition
Time Frame: baseline and end of study (12 weeks)
faecal samples analysed for their microbial composition, aka the presence of bacteria in the stool. The bacteria present will be identified where possible and quantified. The diversity of the microbiota present will be calculated using standard protocols. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Metabolites in serum
Time Frame: baseline and end of study (12 weeks)
Serum samples analysed for their metabolite composition, aka the presence of metabolites in the blood. Those present will be identified where possible and quantified. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Cognition
Time Frame: baseline and end of study (12 weeks)
CANTAB Battery. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Questionnaire measures: appetite as measured by SNAQ
Time Frame: baseline and end of study (12 weeks)
SNAQ: Simplified Nutritional Appetite Questionnaire (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Questionnaire measures: physical activity as measured by IPAQ
Time Frame: baseline and end of study (12 weeks)
IPAQ: international physical activity questionnaire. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Salivary microbiome
Time Frame: baseline and end of study (12 weeks)
saliva samples analysed for their microbial composition, aka the presence of bacteria in the saliva. The bacteria present will be identified where possible and quantified. The diversity of the microbiota present will be calculated using standard protocols. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Urinary microbiome
Time Frame: baseline and end of study (12 weeks)
Urine samples analysed for their microbial composition, aka the presence of bacteria in the urine. The bacteria present will be identified where possible and quantified. The diversity of the microbiota present will be calculated using standard protocols. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Anthropological measures: height
Time Frame: baseline and end of study (12 weeks)
height, measured in centimetres. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)
Anthropological measures: weight
Time Frame: baseline and end of study (12 weeks)
measured in kilograms. (absolute and change from baseline at 12 weeks)
baseline and end of study (12 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Claire Steves, The Department of Twin Research & Genetic Epidemiology

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

April 29, 2021

Primary Completion (ACTUAL)

December 20, 2021

Study Completion (ACTUAL)

December 20, 2021

Study Registration Dates

First Submitted

February 5, 2020

First Submitted That Met QC Criteria

March 12, 2020

First Posted (ACTUAL)

March 16, 2020

Study Record Updates

Last Update Posted (ACTUAL)

October 27, 2022

Last Update Submitted That Met QC Criteria

October 26, 2022

Last Verified

February 1, 2021

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Please see attached document DTR_DataAccess_Policy_0318.pdf for our Data Access Policy.

IPD Sharing Time Frame

The data will become available after the study has been completed and all results analysed. We estimate this to be approximately 2023. The data will remain available for the foreseeable future with no end date in sight at present.

IPD Sharing Access Criteria

Please see attached document DTR_DataAccess_Policy_0318.pdf for our Data Access Policy.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP
  • ICF

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Frailty

Clinical Trials on Prebiotic food supplement

Subscribe