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

Primary Purpose

Sarcopenia, Frailty, Age-Related Sarcopenia

Status
Completed
Phase
Not Applicable
Locations
United Kingdom
Study Type
Interventional
Intervention
Prebiotic food supplement
Protein supplement
Maltrodextrin (placebo)
Sponsored by
King's College London
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Sarcopenia focused on measuring gut microbiome, metabolome, prebiotic

Eligibility Criteria

60 Years - 120 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • Department of Twin Research and Genetics

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment Arm

Placebo Arm

Arm Description

protein supplementation plus prebiotic supplementation

Protein supplementation plus placebo

Outcomes

Primary Outcome Measures

Change in chair rise time
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.

Secondary Outcome Measures

Gripstrength, as measured by dynamometer
A marker of muscle strength, measured in kilograms. Dominant hand will be used. (absolute and change from baseline at 12 weeks)
Microbiome composition
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)
Metabolites in serum
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)
Cognition
CANTAB Battery. (absolute and change from baseline at 12 weeks)
Questionnaire measures: appetite as measured by SNAQ
SNAQ: Simplified Nutritional Appetite Questionnaire (absolute and change from baseline at 12 weeks)
Questionnaire measures: physical activity as measured by IPAQ
IPAQ: international physical activity questionnaire. (absolute and change from baseline at 12 weeks)
Salivary microbiome
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)
Urinary microbiome
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)
Anthropological measures: height
height, measured in centimetres. (absolute and change from baseline at 12 weeks)
Anthropological measures: weight
measured in kilograms. (absolute and change from baseline at 12 weeks)

Full Information

First Posted
February 5, 2020
Last Updated
October 26, 2022
Sponsor
King's College London
Collaborators
Co-sponsor: Guy's and St Thomas' NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT04309292
Brief Title
Protein and Skeletal Muscle in Older Twins: Role of the Gut Microbiome
Acronym
PROMOTe
Official Title
Dietary Protein and Skeletal Muscle in Older Twins - Targeting the Gut Microbiome to Overcome Anabolic Resistance: The PROMOTe Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Completed
Study Start Date
April 29, 2021 (Actual)
Primary Completion Date
December 20, 2021 (Actual)
Study Completion Date
December 20, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King's College London
Collaborators
Co-sponsor: Guy's and St Thomas' NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sarcopenia, Frailty, Age-Related Sarcopenia
Keywords
gut microbiome, metabolome, prebiotic

7. Study Design

Primary Purpose
Prevention
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
71 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Treatment Arm
Arm Type
Experimental
Arm Description
protein supplementation plus prebiotic supplementation
Arm Title
Placebo Arm
Arm Type
Placebo Comparator
Arm Description
Protein supplementation plus placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
Prebiotic food supplement
Intervention Description
Darmocare Pre = trade name Gut microbiome modulator
Intervention Type
Dietary Supplement
Intervention Name(s)
Protein supplement
Intervention Description
commercially available protein supplementation with high leucine content
Intervention Type
Dietary Supplement
Intervention Name(s)
Maltrodextrin (placebo)
Intervention Description
Starchy substance
Primary Outcome Measure Information:
Title
Change in chair rise time
Description
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.
Time Frame
baseline and end of study (12 weeks)
Secondary Outcome Measure Information:
Title
Gripstrength, as measured by dynamometer
Description
A marker of muscle strength, measured in kilograms. Dominant hand will be used. (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)
Title
Microbiome composition
Description
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)
Time Frame
baseline and end of study (12 weeks)
Title
Metabolites in serum
Description
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)
Time Frame
baseline and end of study (12 weeks)
Title
Cognition
Description
CANTAB Battery. (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)
Title
Questionnaire measures: appetite as measured by SNAQ
Description
SNAQ: Simplified Nutritional Appetite Questionnaire (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)
Title
Questionnaire measures: physical activity as measured by IPAQ
Description
IPAQ: international physical activity questionnaire. (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)
Title
Salivary microbiome
Description
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)
Time Frame
baseline and end of study (12 weeks)
Title
Urinary microbiome
Description
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)
Time Frame
baseline and end of study (12 weeks)
Title
Anthropological measures: height
Description
height, measured in centimetres. (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)
Title
Anthropological measures: weight
Description
measured in kilograms. (absolute and change from baseline at 12 weeks)
Time Frame
baseline and end of study (12 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
60 Years
Maximum Age & Unit of Time
120 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Claire Steves
Organizational Affiliation
The Department of Twin Research & Genetic Epidemiology
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Twin Research and Genetics
City
London
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing 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 URL
https://twinsuk.ac.uk/wp-content/uploads/2018/11/DTR_DataAccess_Policy_0318.pdf
Citations:
PubMed Identifier
30036990
Citation
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.
Results Reference
background
PubMed Identifier
34210274
Citation
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.
Results Reference
derived

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

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