Effects of dietary protein distribution and resistance exercise training on muscle health in older adults

ISRCTN ISRCTN64199452
DOI https://doi.org/10.1186/ISRCTN64199452
Secondary identifying numbers RG_15-238
Submission date
05/09/2017
Registration date
27/09/2017
Last edited
05/07/2019
Recruitment status
No longer recruiting
Overall study status
Completed
Condition category
Musculoskeletal Diseases
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data

Plain English summary of protocol

Background and aims
A great deal of evidence indicates that muscle mass and function decline with increasing age, and the design of studies to preserve skeletal muscle has been a major research goal for the last 30 years. Resistance (strengthening) exercise training has been shown to be the most effective way of maintaining muscle function in older age, but given that dietary protein also affects muscle function, it is thought that this too could be an important factor in such interventions. Specifically, there is some evidence to suggest that the distribution of protein may be important – i.e., the amounts of protein consumed at different times of day. The aim of this study is to investigate the effects of two different protein distribution diets in combination with resistance exercise training on muscle-related outcomes.

Who can participate?
Women aged 65 years or older who are able to walk (with or without walking aids).

What does the study involve?
Participants are randomly allocated to either Spread or Pulse protein distribution groups. All participants receive a set of meal plans to follow for the two-week study duration; these either divide daily protein equally across breakfast, lunch and dinner (Spread group), or into a 10:80:10% distribution across the meals (Pulse group). Participants also complete three exercise sessions per week, consisting of 6 sets of 8 repetitions of a leg strengthening exercise at a moderate intensity. They only exercise one leg, and comparisons are made between exercised and non-exercised legs as well as between the protein distribution groups. Small samples from participants’ thigh muscles at the start and end of the study, as well as saliva samples are taken from participants. Participants drink a small amount of water containing a tracer molecule at the start and after one week. Blood samples are taken to measure markers of inflammation, and participants also complete a test of leg strength, at the start and end of the study. Participants are asked to record how well they follow the meal plan, so we can analyse compliance to the intervention.

What are the possible benefits and risks of participating?
Resistance exercise training has consistently been shown to have beneficial effects in older adults, such as increases in muscle size and strength. Participants may find the exercises or the tests of muscle function a little uncomfortable, especially if they are not accustomed to this type of activity. Some people find both the administration of the local anaesthetic and the biopsy procedure uncomfortable, and risks can include bruising, infection or insensitivity of the skin although these risks are very small. The blood sampling may also cause slight discomfort but the procedure is quick and the sampling will be done by a trained member of the study team. The tracer water has been known to cause feelings of dizziness and nausea, although this is unusual.

Where is the study run from?
The study is run by the University of Birmingham (UK), and takes place in the Heritage Building of the Queen Elizabeth Hospital (UK).

When is study starting and how long is it expected to run for?
April 2016 to December 2017

Who is funding the study
MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research (UK)

Who is the main contact?
1. Danielle Thomas
dxt353@bham.ac.uk
2. Dr Carolyn Greig
c.a.greig@bham.ac.uk

Contact information

Ms Danielle Thomas
Scientific

School of Sport Exercise and Rehabilitation Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Dr Carolyn Greig
Public

School of Sport Exercise and Rehabilitation Sciences
University of Birmingham
Birmingham
B15 2TT
United Kingdom

Study information

Study designSingle-centre randomised parallel group trial
Primary study designInterventional
Secondary study designRandomised parallel trial
Study setting(s)Hospital
Study typeQuality of life
Participant information sheet Not available in web format, please use contact details to request a participant information sheet
Scientific titleInfluence of Pulse vs Spread protein distribution in combination with resistance exercise training on muscle protein synthesis, muscle strength and markers of inflammation in older women
Study acronymPRODREX
Study objectivesThere will be a significant difference in muscle health with different protein distributions. Based on previous studies, we hypothesise that improvements will be seen in both groups, however there will be greater improvement in the Pulse group.
Ethics approval(s)West Midlands - Black Country Research Ethics Committee, 18/03/2016, ref 16/WM/0005
Health condition(s) or problem(s) studiedSarcopenia
InterventionParticipants are randomly allocated to one of two groups, and receive a set of meal plans to follow for two weeks. Participants are randomised in advance by a UHB statistician using a computer generated programme and concealed in sequentially numbered opaque envelopes. Neither the investigators nor the participants are blinded following allocation for practical reasons. These plans will provide 1.2 g/kg/d of protein, divided across the day into one of two protein distributions:

Spread: 33:33:33% across breakfast, lunch and dinner
Pulse: 10:80:10% across breakfast, lunch and dinner

All participants will also complete three sessions per week of unilateral resistance exercise training , each session consisting of 6 x 8 reps at 75% 1-RM leg extension.

The main outcome measured is the rate at which muscles make new protein; we will take small samples from participants’ thigh muscles at the start and end of the study, as well as saliva samples, and participants will drink a small amount of water containing a tracer molecule at the start and after one week. We will also take blood samples to measure markers of inflammation, and participants will also complete a test of leg strength, at the start and end of the study. Participants are asked to record how well they follow the meal plan, so we can analyse compliance to the intervention.
Intervention typeSupplement
Primary outcome measureMuscle protein synthesis is measured using D2O tracer, muscle biopsies and saliva samples at baseline and day 14
Secondary outcome measures1. Leg extension strength is measured using 1-RM tests at baseline and day 14
2. Serum inflammatory markers IL-1, IL-6, IL-8, TNF-alpha, and the anti-inflammatory cytokine IL-10, are measured using blood samples taken at baseline and day 14
3. Compliance to diet intervention is measured using self-reported records of daily compliance to meal plans, and 3-day food diary between days 7 and 14
Overall study start date04/08/2015
Completion date30/06/2018

Eligibility

Participant type(s)Healthy volunteer
Age groupSenior
SexFemale
Target number of participants16
Total final enrolment12
Key inclusion criteria1. Aged 65 years or over
2. Female
3. Ambulatory (with or without walking aids)
Key exclusion criteria1. Already engaging in regular exercise (at least twice a week)
2. History of myocardial infarction within previous 2 years
3. Cardiac illness: moderate/ severe aortic stenosis, acute pericarditis, acute myocarditis, aneurysm, severe angina,
4. Clinically significant valvular disease, uncontrolled dysrhythmia, claudication within the previous 10 years
5. Thrombophlebitis or pulmonary embolus within the previous 2 years
6. History of cerebrovascular disease (CVA or TIA) within the previous 2 years
7. Treatment with anticoagulants (Warfarin, rivaroxaban, apixaban, dabigatran) and antiplatelets (dipyridamole, clopidogrel, prasugrel, ticagrelor, glycoprotein IIb/IIIa antagonists). Nb. those regularly taking aspirin will be asked to stop for 3 days prior to biopsies and restart the day after
8. Acute febrile illness within the previous 3 months
9. Severe airflow obstruction
10. Uncontrolled metabolic disease (e.g., thyroid disease or cancer)
11. Significant emotional distress, psychotic illness or depression within the previous 2 years
12. Lower limb fracture sustained within the previous 2 years; upper limb fracture within the previous 6 months; non arthroscopic lower limb joint surgery within the previous 2 years
13. Any reason for loss of mobility for greater than 1 week in the previous 2 months or greater than 2 weeks in the previous 6 months
14. Resting systolic pressure >200 mmHg or resting diastolic pressure >100mmHg
15. Poorly controlled atrial fibrillation
16. Poor (chronic) pain control
17. Moderate/ severe cognitive impairment (MMSE <23)
18. Renal impairment (Stage 4 or 5)
Date of first enrolment18/04/2016
Date of final enrolment31/03/2018

Locations

Countries of recruitment

  • England
  • United Kingdom

Study participating centres

University of Birmingham
School of Sport, Exercise and Rehabilitation Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom
Queen Elizabeth Hospital Birmingham
Queen Elizabeth Hospital Birmingham
Mindelsohn Way
Edgbaston
Birmingham
B15 2WG
United Kingdom

Sponsor information

University of Birmingham
University/education

University of Birmingham
Edgbaston
Birmingham
B15 2TT
England
United Kingdom

ROR logo "ROR" https://ror.org/03angcq70

Funders

Funder type

Charity

MRC-Arthritis Research UK Centre for Musculoskeletal Ageing Research

No information available

Results and Publications

Intention to publish date31/03/2019
Individual participant data (IPD) Intention to shareNo
IPD sharing plan summaryNot expected to be made available
Publication and dissemination planResults of this trial will be submitted for publication in peer reviewed journals. The manuscript will be prepared by the study team led by Dr Carolyn Greig and authorship will be determined by mutual agreement.
IPD sharing planThe datasets generated and/or analysed during the current study during this study will be included in the subsequent results publication.

Study outputs

Output type Details Date created Date added Peer reviewed? Patient-facing?
Basic results 05/07/2019 05/07/2019 No No
Protocol file version V6 10/04/2017 05/07/2019 No No
HRA research summary 28/06/2023 No No

Additional files

ISRCTN64199452_PROTOCOL__10Apr17_V6.pdf
Uploaded 02/04/2019
ISRCTN64199452_Basic_results_05Jul19.pdf
uploaded 05/07/2019

Editorial Notes

05/07/2019: The following changes were made to the trial record:
1. The basic results of this trial have been uploaded as an additional file.
2. The total final enrolment was added.
02/04/2019: Uploaded protocol (not peer reviewed).
26/01/2018: The overall trial end date has been updated from 31/03/2018 to 30/06/2018. The recruitment end date has been updated from 31/12/2017 to 31/03/2018.