Can Creatine Supplementation Improve Body Composition and Physical Function in Rheumatoid Arthritis Patients?

Study Overview
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Brief Summary
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Rheumatoid arthritis (RA) patients typically experience a significant loss of muscle. In healthy individuals, food supplementation with creatine (Cr) increases muscle size and improves physical function and quality of life. The aim of this study is to investigate whether RA patients may benefit similarly. 50 participants will be given a food supplement to take for 12 weeks; this supplement will either be creatine or a placebo (a regular fruit flavoured powder that has no benefits). Over 12 weeks, body fat and muscle size (body composition), physical function, and fitness (aerobic capacity of the heart and lungs to transport oxygen to the exercising muscles) will be tested. In addition, quality of life questionnaires will be completed, disease activity will be assessed and blood samples will be taken. Muscle samples (muscle biopsy) will be obtained, from those who volunteer to provide them, at baseline and post-treatment.

Detailed Description
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Background and aims Rheumatoid arthritis (RA) patients typically experience a significant loss of muscle. This reduces their ability to complete daily tasks and increases disability, as well as increasing the risk to infection and other illness. Exercise is most effective for increasing muscle size and strength, but it is time consuming, expensive and hard work, meaning uptake is poor. So, widely acceptable alternatives are required. The study aims to test a food supplement called creatine. Creatine, often found in meat and fish, make up an essential part of the systems that provide energy to the muscles for movement and exercise. The creatine will be provided as a fruit flavoured powder that participants will mix with water and drink, much like a fruit squash. In healthy individuals, food supplementation with creatine (Cr) increases muscle size and improves physical function and quality of life. The aim of this study is to investigate whether RA patients may benefit similarly Who are the participants? 50 patients with who have stable and controlled RA, are over age 18, with no known kidney problems. What does the study involve? 50 participants will be given a food supplement to take for 12 weeks; this supplement will either be creatine or a placebo (a regular fruit flavoured powder that has no benefits). Participants will be randomly allocated to a group and will not be told which supplement they are taking until the end of the trial. The supplement will be taken as a drink 4 times a day for the first 5 days, and then once a day for the remainder of the 12 weeks. Participants will be asked to attend Bangor University 4 times to have a series of tests done. The four testing points are: before they start supplementation after the 5 days at completion of the 12-weeks of supplementation 12 weeks after completion of the 12 week supplementation period. At all four testing points (1-4) body fat and muscle size (body composition), physical function, and fitness (aerobic capacity of the heart and lungs to transport oxygen to the exercising muscles) will be tested. In addition, quality of life questionnaires will be completed, disease activity will be assessed and blood samples will be taken. Muscle samples (muscle biopsy) will be obtained, from those who volunteer to provide them, at baseline and post-treatment (test points 1 and 3). Body fat and muscle size (body composition) will be assessed using type of X-ray called 'dual-entry X-ray absorptiometry' (DXA) scans and by looking at body water levels. DXA allows the research team to estimate the amount of lean tissue (muscle) and fat that is in the body. The scan is completely painless. Physical function will be assessed using the following tests: strength tests of the knee muscles and hand-grip the Up-and-Go Test (UG) - For the UG, participants are required rise from a seated position on a fixed chair, walk forward to a cone placed 8ft (2.44 m) away, and return to the chair and a seated position. the sit-to-stand in 30 sec test (SST-30) - For the SST-30 participants will rise from the same seated position as during the UG as many times as possible in 30 s whilst keeping their arms folded across the chest. 50-ft walk test - During the 50-ft walk test, time taken to complete the walk along a straight line marked by cones is recorded To assess fitness participants will complete a step test. During the test participants are required to step up and down a 10-inch step at a tempo controlled by a metronome for three x three-minute stages or until the target heart rate (65% of predicted maximum heart rate) is achieved. This test will normally last 3 minutes What are the potential risks and benefits? Risks - A disadvantage of taking part is the time commitment required to participate in the study. Whilst taking the supplement drink will be quick and simple, there are 4 testing sessions which may 2 hours in which participants must attend at Bangor University. Any travel expenses participants incur for participating in this study will be paid for. Creatine supplementation will cause some weight gain; in the short-term this is due to water retention by the muscle and in the long-term this is due to an increase in muscle size. Previous research, including research with RA patients, has found no adverse side effects that can be linked to the creatine supplementation. There are anecdotal reports of creatine supplementation causing muscle cramps, stomach and heart problems; however no evidence has ever linked these directly to the creatine itself. There is also a slight possibility that the muscle biopsy site (where the muscle is taken) could bruise and be sore but this is quite rare and in fact most people report only a short term slight ache after the biopsy. There is also an exposure to radiation (emission of energy) from the DXA scan, though this is only a small amount. However, because of this radiation pregnant women are not allowed to part in the study. Benefits - Taking creatine supplements will increase muscle strength and improve physical function and quality of life. Participants will receive creatine supplementation regardless of which group they are initially put into. Participants will also be informed about their fitness levels and will receive advice on how to improve these. The standard DXA can inform the investigaters of a disease in the bone that can increase the risk of fractures (osteoporosis) that patients might not know they had. Who is running the study and how long will it last? The study will commence in January 2012 and is being undertaken by the School of Sport, Health and Exericse Sciences (SSHES) at Bangor University, Wales, in association with the Rheumatology department at Ysbyty Gwynedd Hospital, Bangor. Who is funding the study? The study is being funded by Betsi Cadwalader University Health Board. The study is expected to finish within an 18 month time frame, with recruiting open for a year or until 50 patients have been found. Who is the main contact? Prof Andrew Lemmey a.lemmey@bangor.ac.uk Dr Tom O'Brien thomas.obrien@bangor.ac.uk Thomas Wilkinson, thomas.wilkinson@bangor.ac.uk

Official Title
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Can Creatine Supplementation Improve Body Composition and Physical Function in Rheumatoid Arthritis Patients? A Randomised Controlled Pilot Trial

Conditions
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Rheumatoid Arthritis

Intervention / Treatment
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* Dietary Supplement: Creatine
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: fulfil the American Rheumatism Association 1987 revised criteria for the diagnosis of RA be functional class I or II be age 18 years or over Exclusion Criteria: be cognitively impaired; (b) have any other cachectic diseases and any condition preventing safe participation in the study have a glomerular filtration rate above 60mL/min/1.73m2, assessed from medical records, and no other evidence of kidney damage be taking drugs or other nutritional supplements known to increase muscle mass be participating in regular and intense physical training program be pregnant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Creatine<br>Creatine, often found in meat and fish, make up an essential part of the systems that provide energy to the muscles for movement and exercise. | Dietary Supplement: Creatine<br>* Creatine, often found in meat and fish, make up an essential part of the systems that provide energy to the muscles for movement and exercise.<br>* Other names: SN: 5055534301999 BB: 09/2014;|
| Placebo Comparator: Fruit powder drink<br>A regular fruit flavoured powder that has no benefits | Dietary Supplement: Placebo<br> <br> * Other names: Manufactured by Foster Clarks Ltd (www.fosterclark.com);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 'Objectively assessed whole body function' | Physical function will be assessed using the following tests: strength tests of the knee muscles and hand-grip the Up-and-Go Test (UG) - For the UG, participants are required rise from a seated position on a fixed chair, walk forward to a cone placed 8ft (2.44 m) away, and return to the chair and a seated position. the sit-to-stand in 30 sec test (SST-30) - For the SST-30 participants will rise from the same seated position as during the UG as many times as possible in 30 s whilst keeping their arms folded across the chest. 50-ft walk test - During the 50-ft walk test, time taken to complete the walk along a straight line marked by cones is recorded To assess fitness participants will complete the Siconolfi step test. | Measured at Baseline, Day 6, Week 12, Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in body composition | Body fat and muscle size (body composition) will be assessed using type of X-ray called 'dual-entry X-ray absorptiometry' (DXA) scans and by looking at body water levels. DXA allows the research team to estimate the amount of lean tissue (muscle) and fat that is in the body. The scan is completely painless. | Baseline, Day 6, Week 12, Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Rheumatoid Arthritis, Arthritis, Rheumatology, Creatine