Effect of Supplementation With Creatine on the Recovery of Ischemic Stroke

Official title

Effect of Supplementation With Creatine on the Early Recovery of Ischemic Stroke: A Randomized Clinical Trial

Overview

Stroke is a leading cause of disability and the second leading cause of death worldwide. Most strokes are ischemic, caused by acute arterial occlusion. Post-stroke treatment focuses on secondary prevention and rehabilitation, but few treatments address functional recovery. Creatine, a supplement known for improving physical performance, may aid in the recovery of stroke patients, reducing sarcopenia and improving strength among other effects. This pilot study will investigate the effectiveness of creatine supplementation in enhancing physical and functional recovery in ischemic stroke patients. The study will involve a randomized, double-blind clinical trial comparing creatine monohydrate to a placebo.

Detailed description

Stroke is one of the most impactful health conditions worldwide, currently being the leading cause of disability and the second leading cause of death globally. Approximately 85-90% of strokes are ischemic, primarily caused by acute arterial occlusion, leading to an area of cerebral, spinal, or retinal infarction. The size of the lesion depends on the affected blood vessel and the duration of the occlusion, as well as cerebral autoregulation, blood pressure, blood sugar levels, and many other factors. After the acute phase, treatment is based on secondary prevention and rehabilitation, with few treatments currently available that focus on functional recovery once the infarction has occurred. Stroke survivors experience a loss of functionality, a decline in physical capacity associated with a decrease in muscle mass, sarcopenia, cognitive impairment, and an increase in anxiety and depressive symptoms.

Creatine is a widely studied nutritional supplement, mainly in athletes, where it has been shown to improve training adaptation and physical performance. Its effects on energy metabolism, as an anti-inflammatory, and on calcium homeostasis have been described. There are also studies indicating possible musculoskeletal benefits in the elderly population. Given its role in improving physical performance and muscle mass, considering the significant impact of these conditions on patients who have suffered an ischemic stroke, and considering its antioxidant and anti-inflammatory effects, we propose a pilot study to determine the effectiveness of creatine supplementation in stroke patients. This supplementation could potentially lead to greater physical and functional recovery following an ischemic stroke.

A randomized, double-blind clinical trial will be conducted. The trial will include a group supplemented with creatine monohydrate at a dose of 0.3 g/kg/day for 7 days, followed by 0.1 g/kg/day for 12 weeks, alongside standard clinical practice; and a control group supplemented with a placebo (corn starch maltodextrin), following the same protocol and doses.

Interventions

• Dietary supplement Creatine monohydrate
  Creatine monohydrate. Guinama brand with CE marking. Code 89823.
• Other Placebo
  Dextrinomaltose. Guinama brand with CE marking. Code 91146.

Primary outcome measures

• Physical performance [Time frame: 3 months, 6 months]

Secondary outcome measures (12)

• Physical performance using Test "timed up and go" (TUG). [Time frame: 3 months, 6 months]
• Maximum muscle strength [Time frame: 3 months, 6 months]
• Arm and leg muscle strength [Time frame: 3 months, 6 months]
• Balance and stability [Time frame: 3 months, 6 months]
• Functional impact [Time frame: 3 months, 6 months]
• Performance in basic activities of daily living [Time frame: 3 and 6 months]
• Cognitive assessment [Time frame: 3 months]
• Quality of life measured by EuroQol 5D [Time frame: 3 months, 6 months]
• Anxiety and depression symptoms [Time frame: 3 months]
• Appendicular skeletal muscle mass [Time frame: 3 months]
• Total skeletal muscle mass [Time frame: 3 months]
• Appendicular body fat [Time frame: 3 months]

Eligibility criteria

Inclusion criteria

• Age between 18 and 80 years
• Recent diagnosis of ischemic stroke (from 24 hours to 5 days) .
• Neurological deficit due to the stroke that affects mobility (paresis and/or ataxia) and requires motor rehabilitation.
• Ability to understand and sign the informed consent form, or failing that, have sufficient support to carry out the correct follow-up of the study.

Exclusion criteria

• Moderate-severe disability prior to stroke, defined by an mRS>2.
• Unstable or severe clinical situation that prevents active rehabilitation.
• Neurological deficit due to stroke that prevents walking without help from another person. The use of support with a cane, crutch or walker is permitted.
• Moderate or severe dysphagia that makes therapeutic adherence difficult.
• Use of creatine supplements in the last 3 months, or use of anabolic products in the last 3 months.
• Severe kidney disease (GFR <30ml/min/1.73 m2).
• Musculoskeletal pathology that prevents assessment of muscle strength. For example: fractures, severe osteoarthritis, ligament tears or tendinopathies.
• History of allergic reactions to creatine.
• Pregnancy or breastfeeding.
• Simultaneous participation in another clinical trial.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Spain · 1 center

• IdISBa — Palma de Mallorca

Publications

• Bender A, Samtleben W, Elstner M, Klopstock T. Long-term creatine supplementation is safe in aged patients with Parkinson disease. Nutr Res. 2008 Mar;28(3):172-8. doi: 10.1016/j.nutres.2008.01.001. PMID 19083405
• Gualano B, de Salles Painelli V, Roschel H, Lugaresi R, Dorea E, Artioli GG, Lima FR, da Silva ME, Cunha MR, Seguro AC, Shimizu MH, Otaduy MC, Sapienza MT, da Costa Leite C, Bonfa E, Lancha Junior AH. Creatine supplementation does not impair kidney function in type 2 diabetic patients: a randomized, double-blind, placebo-controlled, clinical trial. Eur J Appl Physiol. 2011 May;111(5):749-56. doi: PMID 20976468
• Pan JW, Takahashi K. Cerebral energetic effects of creatine supplementation in humans. Am J Physiol Regul Integr Comp Physiol. 2007 Apr;292(4):R1745-50. doi: 10.1152/ajpregu.00717.2006. Epub 2006 Dec 21. PMID 17185404
• McMorris T, Mielcarz G, Harris RC, Swain JP, Howard A. Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2007 Sep;14(5):517-28. doi: 10.1080/13825580600788100. PMID 17828627
• Turner CE, Byblow WD, Gant N. Creatine supplementation enhances corticomotor excitability and cognitive performance during oxygen deprivation. J Neurosci. 2015 Jan 28;35(4):1773-80. doi: 10.1523/JNEUROSCI.3113-14.2015. PMID 25632150
• Butchart S, Candow DG, Forbes SC, Mang CS, Gordon JJ, Ko J, Deprez D, Chilibeck PD, Ditor DS. Effects of Creatine Supplementation and Progressive Resistance Training in Stroke Survivors. Int J Exerc Sci. 2022 Aug 1;15(2):1117-1132. doi: 10.70252/EKHJ1489. eCollection 2022. PMID 35992184
• Forbes SC, Cordingley DM, Cornish SM, Gualano B, Roschel H, Ostojic SM, Rawson ES, Roy BD, Prokopidis K, Giannos P, Candow DG. Effects of Creatine Supplementation on Brain Function and Health. Nutrients. 2022 Feb 22;14(5):921. doi: 10.3390/nu14050921. PMID 35267907
• Solis MY, Artioli GG, Otaduy MCG, Leite CDC, Arruda W, Veiga RR, Gualano B. Effect of age, diet, and tissue type on PCr response to creatine supplementation. J Appl Physiol (1985). 2017 Aug 1;123(2):407-414. doi: 10.1152/japplphysiol.00248.2017. Epub 2017 Jun 1. PMID 28572496

Identifiers

NCT: NCT06576466 · PROSALUT2023-27

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗