- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04309292
Protein and Skeletal Muscle in Older Twins: Role of the Gut Microbiome (PROMOTe)
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
Status
Conditions
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
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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London, United Kingdom
- Department of Twin Research and Genetics
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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
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Darmocare Pre = trade name Gut microbiome modulator
commercially available protein supplementation with high leucine content
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PLACEBO_COMPARATOR: Placebo Arm
Protein supplementation plus placebo
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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.
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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)
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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)
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Questionnaire measures: appetite as measured by SNAQ
Time Frame: baseline and end of study (12 weeks)
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SNAQ: Simplified Nutritional Appetite Questionnaire (absolute and change from baseline at 12 weeks)
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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)
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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)
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baseline and end of study (12 weeks)
|
Urinary microbiome
Time Frame: baseline and end of study (12 weeks)
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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)
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height, measured in centimetres.
(absolute and change from baseline at 12 weeks)
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baseline and end of study (12 weeks)
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Anthropological measures: weight
Time Frame: baseline and end of study (12 weeks)
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measured in kilograms.
(absolute and change from baseline at 12 weeks)
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baseline and end of study (12 weeks)
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Claire Steves, The Department of Twin Research & Genetic Epidemiology
Publications and helpful links
General Publications
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (ACTUAL)
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ACTUAL)
Study Record Updates
Last Update Posted (ACTUAL)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1234 (Department of Defense)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- STUDY_PROTOCOL
- SAP
- ICF
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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.
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