Clinical trial NCT06576466: 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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Stroke, Ischemic
Keywords: stroke
creatine
sarcopenia
Lead sponsor: Fundació d'investigació Sanitària de les Illes Balears
Sponsor class: OTHER_GOV
First posted: 2024-08-28
Enrollment: 92
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Primary outcomes:
measure: Physical performance
timeFrame: 3 months, 6 months
Secondary outcomes:
measure: Physical performance using Test "timed up and go" (TUG).
timeFrame: 3 months, 6 months
measure: Maximum muscle strength
timeFrame: 3 months, 6 months
measure: Arm and leg muscle strength
timeFrame: 3 months, 6 months
measure: Balance and stability
timeFrame: 3 months, 6 months
measure: Functional impact
timeFrame: 3 months, 6 months
measure: Performance in basic activities of daily living
timeFrame: 3 and 6 months
measure: Cognitive assessment
timeFrame: 3 months
measure: Quality of life measured by EuroQol 5D
timeFrame: 3 months, 6 months
measure: Anxiety and depression symptoms
timeFrame: 3 months
measure: Appendicular skeletal muscle mass
timeFrame: 3 months
measure: Total skeletal muscle mass
timeFrame: 3 months
measure: Appendicular body fat
timeFrame: 3 months
measure: Total body fat
timeFrame: 3 months
measure: Nutritional status
timeFrame: 3 months, 6 months
measure: Number of falls.
timeFrame: 3 months, 6 months
measure: Geriatric Nutritional Risk Index (GNRI) score
timeFrame: 3 months, 6 months
measure: Ventricular strain change
timeFrame: 3 months
measure: Ejection fraction change
timeFrame: 3 months
measure: Adverse events
timeFrame: From enrollment to the end of treatment at 6 months
Other outcomes:
Locations:
city: Palma De Mallorca
country: Spain
facility: IdISBa
state: Illes Balears
Study officials:
affiliation: Fundació d'investigació Sanitària de les Illes Balears
name: Raquel Delgado Mederos, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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: 10.1007/s00421-010-1676-3. Epub 2010 Oct 26.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: Chrusch MJ, Chilibeck PD, Chad KE, Davison KS, Burke DG. Creatine supplementation combined with resistance training in older men. Med Sci Sports Exerc. 2001 Dec;33(12):2111-7. doi: 10.1097/00005768-200112000-00021.
citation: Scherbakov N, von Haehling S, Anker SD, Dirnagl U, Doehner W. Stroke induced Sarcopenia: muscle wasting and disability after stroke. Int J Cardiol. 2013 Dec 10;170(2):89-94. doi: 10.1016/j.ijcard.2013.10.031. Epub 2013 Oct 14.
citation: Coleman ER, Moudgal R, Lang K, Hyacinth HI, Awosika OO, Kissela BM, Feng W. Early Rehabilitation After Stroke: a Narrative Review. Curr Atheroscler Rep. 2017 Nov 7;19(12):59. doi: 10.1007/s11883-017-0686-6.
citation: Balestrino M. Role of Creatine in the Heart: Health and Disease. Nutrients. 2021 Apr 7;13(4):1215. doi: 10.3390/nu13041215.
citation: Schroder H, Fito M, Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Lamuela-Raventos R, Ros E, Salaverria I, Fiol M, Lapetra J, Vinyoles E, Gomez-Gracia E, Lahoz C, Serra-Majem L, Pinto X, Ruiz-Gutierrez V, Covas MI. A short screener is valid for assessing Mediterranean diet adherence among older Spanish men and women. J Nutr. 2011 Jun;141(6):1140-5. doi: 10.3945/jn.110.135566. Epub 2011 Apr 20.
citation: Scheitz JF, Sposato LA, Schulz-Menger J, Nolte CH, Backs J, Endres M. Stroke-Heart Syndrome: Recent Advances and Challenges. J Am Heart Assoc. 2022 Sep 6;11(17):e026528. doi: 10.1161/JAHA.122.026528. Epub 2022 Sep 3.