Effect of Supplementation With Creatine on the Recovery of Ischemic Stroke (SUCRE)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Dietary supplement: Creatine monohydrate; Other: 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.

• Study Type: Interventional
• Enrollment (Estimated): 92
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Raquel Delgado Mederos, PhD; Phone Number: 0034971205234; Email: raquel.delgado@ssib.es
• Study Contact Backup: Name: Eduard Bargay Pizarro, MD; Phone Number: 34 971 20 52 34; Email: eduard.bargay@ssib.es

Study Locations

• Spain
  • Illes Balears
    • Palma De Mallorca, Illes Balears, Spain, 07120
      • Recruiting
      • IdISBa
      • Contact: Raquel Delgado Mederos, PhD; Phone Number: 971 20 52 34; Email: raquel.delgado@ssib.es
      • Principal Investigator: Raquel Delgado Mederos, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Creatine monohydrate; Creatine monohydrate. Guinama brand with CE marking. Code 89823.	Dietary supplement: Creatine monohydrate; Creatine monohydrate. Guinama brand with CE marking. Code 89823.
Placebo Comparator: Dextromaltose; Dextrinomaltose. Guinama brand with CE marking. Code 91146.	Other: Placebo; Dextrinomaltose. Guinama brand with CE marking. Code 91146.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical performance	To analyze the improvement in physical performance, at 3 months (at the end of the intervention) and at 6 months, measured by the 6-Minute Walking Test (6MW).	3 months, 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical performance using Test "timed up and go" (TUG).	Test "timed up and go" (TUG).	3 months, 6 months
Maximum muscle strength	Maximum muscle strength, measured by manual dynamometer (Kilograms). Grip strength, biceps, triceps, deltoids, psoas, quadriceps and hamstrings will be assessed.	3 months, 6 months
Arm and leg muscle strength	Measured by the score on items 5 and 6 of the National institute of Health Stroke Scale (NIHSS) where the score range is from 0 to 4. A higher score corresponds to a worse performance.	3 months, 6 months
Balance and stability	Balance and stability measured using the Postural Assessment Scale for Stroke Patients (PASS). The scale includes 12 items, which are divided into two categories: maintaining a posture (static balance) and changing a posture (dynamic balance). Higher scores indicate better postural control and balance.	3 months, 6 months
Functional impact	Functional impact measured by the Modified Rankin Scale (mRS). The mRS is a commonly used scale to measure the degree of disability or dependence in daily activities of people who have suffered a stroke. The mRS is scored on a scale from 0 to 6, with higher scores indicating greater disability	3 months, 6 months
Performance in basic activities of daily living	Barthel Scale. The Barthel Index is a scale used to measure a person's performance in basic activities of daily living (ADLs) and assess functional independence	3 and 6 months
Cognitive assessment	Cognitive assessment using the Montreal cognitive assessment (MoCA) test. The MoCA is a tool used to assess cognitive impairment in various domains, including memory, attention, language, and executive function. A higher score means a better outcome.	3 months
Quality of life measured by EuroQol 5D	Quality of life assessment using the "EuroQol 5D". EuroQoL 5D is a standardized tool used to assess health-related quality of life. A higher score corresponds to worse quality of life.	3 months, 6 months
Anxiety and depression symptoms	Assessment of anxiety and depression symptoms using the HADS (Hospital Anxiety and Depression Scale). Both the Anxiety subscale and the Depression subscale range from 0 to 21. Higher scores on either subscale indicate worse outcomes (more severe anxiety or depression).	3 months
Appendicular skeletal muscle mass	Measurement of appendicular (arms and legs) skeletal muscle mass change from baseline, using DXA (dual-energy X-ray absorptiometry) measured in kilograms. A higher skeletal muscle mass means a better outcome.	3 months
Total skeletal muscle mass	Measurement of total skeletal muscle mass change from baseline, using DXA (dual-energy X-ray absorptiometry) measured in kilograms. A higher skeletal muscle mass means a better outcome.	3 months
Appendicular body fat	Measurement of appendicular (arms and legs) and total body fat change from baseline, using DXA (dual-energy X-ray absorptiometry) measured in kilograms. A lower fat mass means a better outcome.	3 months
Total body fat	Measurement of total body fat change from baseline, using DXA (dual-energy X-ray absorptiometry) measured in kilograms. A lower fat mass means a better outcome.	3 months
Nutritional status	Measurement of nutritional status change by phase angle using a bioelectrical impedance analysis. A higher phase angle means a better outcome. Outcome units are degrees.	3 months, 6 months
Number of falls.	Number of falls since last visit.	3 months, 6 months
Geriatric Nutritional Risk Index (GNRI) score	Geriatric Nutritional Risk Index (GNRI) score. The following formula is used: [1.489 × serum albumin (g/L)] + (41.7 × weight (kg)/ideal weight (kg)).	3 months, 6 months
Ventricular strain change	Effect of creatine on cardiac damage secondary to stroke measured using ventricular strain measurement (percentage). A lower strain corresponds to a worse outcome.	3 months
Ejection fraction change	Effect of creatine on cardiac damage secondary to stroke measured using ejection fraction (EF) measurement (percentage). A lower EF corresponds to a worse outcome.	3 months
Adverse events	To assess the occurrence of any adverse events in any of the intervention groups.	From enrollment to the end of treatment at 6 months

Collaborators and Investigators

• Sponsor: Fundació d'investigació Sanitària de les Illes Balears
• Collaborators: Comunidad Autónoma de las Islas Baleares (Dirección General de Investigación en Salud, Formación y Acreditación)
• Investigators: Principal Investigator: Raquel Delgado Mederos, PhD, Fundació d'investigació Sanitària de les Illes Balears

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Balestrino M. Role of Creatine in the Heart: Health and Disease. Nutrients. 2021 Apr 7;13(4):1215. doi: 10.3390/nu13041215.
• 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.
• 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.

Helpful Links

• Stroke among top 10 causes of death according to the Word Health Organization (WHO).

Study record dates

Study Major Dates

• Study Start (Actual): September 27, 2024
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: August 22, 2024
• First Submitted That Met QC Criteria: August 26, 2024
• First Posted (Actual): August 28, 2024

Study Record Updates

• Last Update Posted (Estimated): July 8, 2025
• Last Update Submitted That Met QC Criteria: July 2, 2025
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: stroke; sarcopenia; creatine
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Ischemic Stroke; Stroke; Ischemia
• Other Study ID Numbers: PROSALUT2023-27

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data obtained through this study may be provided to qualified researchers with academic interest in Creatine supplementation and stroke. Data will be shared subject to acceptance by the research team. Data or samples shared will be coded.
• IPD Sharing Time Frame: Data requests can be submitted starting 12 months after article publication and the data will be made accessible for up to 24 months.
• IPD Sharing Access Criteria: Access to trial IPD can be requested by qualified researchers. Data will be shared subject to acceptance by the research team.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No