Ischemic Stroke Nutrition Intervention Study

NCT06817512 | Active Not Recruiting

• 1 other identifier: HMUIRB2024027
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 3

Brief Summary

The primary goal of this clinical trial is to assess whether vitamin K2 supplementation can effectively improve skeletal muscle and neurological function in patients with ischemic stroke. The main questions it aims to answer are: 1. Does supplementation with vitamin K2 improve the subjects' muscle strength and muscle mass? 2. Can supplementation with vitamin K2 improve the subjects' neurological function after a stroke? Researchers will compare vitamin K2 supplements with a placebo to observe whether vitamin K2 supplementation can improve skeletal muscle and neurological function in patients with ischemic stroke. Participants will: 1. Take vitamin K2 (MK-7) or a placebo daily for 1 year. 2. Attend face-to-face visits and provide biological samples and relevant data at 0, 3, 6, and 12 months. At 9 months, the visit will be online. After the intervention, follow-up will continue for 1 year to observe the long-term effects.

Conditions

Ischemic Stroke

Keywords

Vitamin K2; Skeletal Muscle; Neurological Function; Ischemic Stroke

Outcome Measures

Primary Outcomes (1)

• Handgrip strength

  Handgrip strength was measured in participants using an electronic dynamometer.

  Measurements were taken at 0 (baseline), 3, 6, and 12 (end of intervention) months.

Secondary Outcomes (36)

• Sustained effects of the intervention on handgrip strength

  Measurements were recorded at 24 months (end of follow-up).

• National Institute of Health Stroke Scale (NIHSS) score

  Measurements were taken at 0 (baseline), 3, 6, 9, 12 (end of intervention), and 24 (end of follow-up) months.

• Modified Rankin Scale (mRS) score

  Measurements were taken at 0 (baseline), 3, 6, 9, 12 (end of intervention), and 24 (end of follow-up) months.

• Mini-Mental State Examination (MMSE) score

  Measurements were taken at 0 (baseline), 3, 6, 9, 12 (end of intervention), and 24 (end of follow-up) months.

• Change in ischemic lesion volume

  Measurements were taken at 0 (baseline) and 12 (end of intervention) months.

Study Arms (2)

Vitamin K2

EXPERIMENTAL

Vitamin K2 (menaquinone-7), 300µg/d, one capsule per day

Dietary Supplement: Vitamin K2

Placebo Control

PLACEBO COMPARATOR

Placebo with similar appearance and taste, one capsule per day

Dietary Supplement: Placebo

Interventions

Vitamin K2 DIETARY_SUPPLEMENT

Vitamin K2 (MK-7) 300µg/d for 1 year

Vitamin K2

Placebo DIETARY_SUPPLEMENT

Placebo for 1 year

Placebo Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Participants who meet all the following conditions will be included in the trial:
• Men or women aged ≥ 18 years.
• Patients with recent ischemic stroke（first or recurrent stroke no more than 7 days before admission）without significant residual limb paralysis, NIHSS score between 2-15, and muscle strength graded 2-4.
• The patient and their legal guardian (or legally acceptable representative) voluntarily sign the informed consent form.

You may not qualify if:

• Participants who meet any of the following conditions will be excluded from the trial:
• Presence of consciousness disorders, aphasia, or swallowing disorders.
• The diagnosis or suspicion of cerebral hemorrhage, atrial fibrillation, or other factors leading to cardiogenic cerebral infarction.
• Coagulation dysfunction or use of vitamin K antagonists.
• Suffering from chronic gastrointestinal malabsorption (such as celiac disease, short bowel syndrome), severe congestive heart failure, malignant hypertension, severe liver and kidney dysfunction, persistent malignant tumors (continuous treatment, or diagnosis of malignant tumors\<5 years), or other related diseases considered by researchers that seriously affect the patient's survival.
• Having musculoskeletal diseases or cognitive impairment before the stroke.
• Currently using or planning to use non research approved dietary supplements during the study period.
• Currently using or planning to use drugs that affect cognitive or neurological function during the research period.
• Restricted normal eating or currently receiving enteral or parenteral nutrition support.
• Contraindications for MRI and other examinations.
• Currently pregnant or planning pregnancy, currently breastfeeding.
• Participated in a clinical trial using experimental drugs or devices within the past 3 months.

Sponsors & Collaborators

• Harbin Medical University: lead

Study Sites (3)

The First Affiliated Hospital of Harbin Medical University

Harbin, Heilongjiang, 150001, China

Location

Hongqi Hospital Affiliated to Mudanjiang Medical University

Mudanjiang, Heilongjiang, 157000, China

Location

The Second Affiliated Hospital of Qiqihar Medical University

Qiqihar, Heilongjiang, 161006, China

Location

Related Publications (28)

• Ohsaki Y, Shirakawa H, Miura A, Giriwono PE, Sato S, Ohashi A, Iribe M, Goto T, Komai M. Vitamin K suppresses the lipopolysaccharide-induced expression of inflammatory cytokines in cultured macrophage-like cells via the inhibition of the activation of nuclear factor kappaB through the repression of IKKalpha/beta phosphorylation. J Nutr Biochem. 2010 Nov;21(11):1120-6. doi: 10.1016/j.jnutbio.2009.09.011. Epub 2010 Feb 9.

  PMID: 20149620 BACKGROUND

• Tsang CK, Kamei Y. Novel effect of vitamin K(1) (phylloquinone) and vitamin K(2) (menaquinone) on promoting nerve growth factor-mediated neurite outgrowth from PC12D cells. Neurosci Lett. 2002 Apr 19;323(1):9-12. doi: 10.1016/s0304-3940(01)02550-2.

  PMID: 11911978 BACKGROUND

• Gely-Pernot A, Coronas V, Harnois T, Prestoz L, Mandairon N, Didier A, Berjeaud JM, Monvoisin A, Bourmeyster N, De Frutos PG, Philippe M, Benzakour O. An endogenous vitamin K-dependent mechanism regulates cell proliferation in the brain subventricular stem cell niche. Stem Cells. 2012 Apr;30(4):719-31. doi: 10.1002/stem.1045.

  PMID: 22290807 BACKGROUND

• Zhong Z, Wang Y, Guo H, Sagare A, Fernandez JA, Bell RD, Barrett TM, Griffin JH, Freeman RS, Zlokovic BV. Protein S protects neurons from excitotoxic injury by activating the TAM receptor Tyro3-phosphatidylinositol 3-kinase-Akt pathway through its sex hormone-binding globulin-like region. J Neurosci. 2010 Nov 17;30(46):15521-34. doi: 10.1523/JNEUROSCI.4437-10.2010.

  PMID: 21084607 BACKGROUND

• Shibata M, Kumar SR, Amar A, Fernandez JA, Hofman F, Griffin JH, Zlokovic BV. Anti-inflammatory, antithrombotic, and neuroprotective effects of activated protein C in a murine model of focal ischemic stroke. Circulation. 2001 Apr 3;103(13):1799-805. doi: 10.1161/01.cir.103.13.1799.

  PMID: 11282913 BACKGROUND

• Carrie I, Belanger E, Portoukalian J, Rochford J, Ferland G. Lifelong low-phylloquinone intake is associated with cognitive impairments in old rats. J Nutr. 2011 Aug;141(8):1495-501. doi: 10.3945/jn.110.137638. Epub 2011 Jun 8.

  PMID: 21653572 BACKGROUND

• Carrie I, Portoukalian J, Vicaretti R, Rochford J, Potvin S, Ferland G. Menaquinone-4 concentration is correlated with sphingolipid concentrations in rat brain. J Nutr. 2004 Jan;134(1):167-72. doi: 10.1093/jn/134.1.167.

  PMID: 14704312 BACKGROUND

• Viegas CS, Rafael MS, Enriquez JL, Teixeira A, Vitorino R, Luis IM, Costa RM, Santos S, Cavaco S, Neves J, Macedo AL, Willems BA, Vermeer C, Simes DC. Gla-rich protein acts as a calcification inhibitor in the human cardiovascular system. Arterioscler Thromb Vasc Biol. 2015 Feb;35(2):399-408. doi: 10.1161/ATVBAHA.114.304823. Epub 2014 Dec 23.

  PMID: 25538207 BACKGROUND

• Harshman SG, Shea MK. The Role of Vitamin K in Chronic Aging Diseases: Inflammation, Cardiovascular Disease, and Osteoarthritis. Curr Nutr Rep. 2016 Jun;5(2):90-98. doi: 10.1007/s13668-016-0162-x. Epub 2016 Mar 31.

  PMID: 27648390 BACKGROUND

• Lees JS, Chapman FA, Witham MD, Jardine AG, Mark PB. Vitamin K status, supplementation and vascular disease: a systematic review and meta-analysis. Heart. 2019 Jun;105(12):938-945. doi: 10.1136/heartjnl-2018-313955. Epub 2018 Dec 4.

  PMID: 30514729 BACKGROUND

• Ronning SB, Pedersen ME, Berg RS, Kirkhus B, Rodbotten R. Vitamin K2 improves proliferation and migration of bovine skeletal muscle cells in vitro. PLoS One. 2018 Apr 4;13(4):e0195432. doi: 10.1371/journal.pone.0195432. eCollection 2018.

  PMID: 29617432 BACKGROUND

• Mladenka P, Macakova K, Kujovska Krcmova L, Javorska L, Mrstna K, Carazo A, Protti M, Remiao F, Novakova L; OEMONOM researchers and collaborators. Vitamin K - sources, physiological role, kinetics, deficiency, detection, therapeutic use, and toxicity. Nutr Rev. 2022 Mar 10;80(4):677-698. doi: 10.1093/nutrit/nuab061.

  PMID: 34472618 BACKGROUND

• Freeman AM, Morris PB, Barnard N, Esselstyn CB, Ros E, Agatston A, Devries S, O'Keefe J, Miller M, Ornish D, Williams K, Kris-Etherton P. Trending Cardiovascular Nutrition Controversies. J Am Coll Cardiol. 2017 Mar 7;69(9):1172-1187. doi: 10.1016/j.jacc.2016.10.086.

  PMID: 28254181 BACKGROUND

• Droujinine IA, Meyer AS, Wang D, Udeshi ND, Hu Y, Rocco D, McMahon JA, Yang R, Guo J, Mu L, Carey DK, Svinkina T, Zeng R, Branon T, Tabatabai A, Bosch JA, Asara JM, Ting AY, Carr SA, McMahon AP, Perrimon N. Proteomics of protein trafficking by in vivo tissue-specific labeling. Nat Commun. 2021 Apr 22;12(1):2382. doi: 10.1038/s41467-021-22599-x.

  PMID: 33888706 BACKGROUND

• de Freitas GB, Lourenco MV, De Felice FG. Protective actions of exercise-related FNDC5/Irisin in memory and Alzheimer's disease. J Neurochem. 2020 Dec;155(6):602-611. doi: 10.1111/jnc.15039. Epub 2020 Jun 2.

  PMID: 32396989 BACKGROUND

• Febbraio MA, Pedersen BK. Who would have thought - myokines two decades on. Nat Rev Endocrinol. 2020 Nov;16(11):619-620. doi: 10.1038/s41574-020-00408-7. No abstract available.

  PMID: 32839577 BACKGROUND

• Sun Y, Zehr EP. Training-Induced Neural Plasticity and Strength Are Amplified After Stroke. Exerc Sport Sci Rev. 2019 Oct;47(4):223-229. doi: 10.1249/JES.0000000000000199.

  PMID: 31283528 BACKGROUND

• Park JG, Lee KW, Kim SB, Lee JH, Kim YH. Effect of Decreased Skeletal Muscle Index and Hand Grip Strength on Functional Recovery in Subacute Ambulatory Stroke Patients. Ann Rehabil Med. 2019 Oct;43(5):535-543. doi: 10.5535/arm.2019.43.5.535. Epub 2019 Oct 31.

  PMID: 31693843 BACKGROUND

• Jones TA. Motor compensation and its effects on neural reorganization after stroke. Nat Rev Neurosci. 2017 May;18(5):267-280. doi: 10.1038/nrn.2017.26. Epub 2017 Mar 23.

  PMID: 28331232 BACKGROUND

• Madureira S, Guerreiro M, Ferro JM. Dementia and cognitive impairment three months after stroke. Eur J Neurol. 2001 Nov;8(6):621-7. doi: 10.1046/j.1468-1331.2001.00332.x.

  PMID: 11784347 BACKGROUND

• Guo J, Wang J, Sun W, Liu X. The advances of post-stroke depression: 2021 update. J Neurol. 2022 Mar;269(3):1236-1249. doi: 10.1007/s00415-021-10597-4. Epub 2021 May 30.

  PMID: 34052887 BACKGROUND

• Wechsler LR, Adeoye O, Alemseged F, Bahr-Hosseini M, Deljkich E, Favilla C, Fisher M, Grotta J, Hill MD, Kamel H, Khatri P, Lyden P, Mirza M, Nguyen TN, Samaniego E, Schwamm L, Selim M, Silva G, Yavagal DR, Yenari MA, Zachrison KS, Boltze J, Yaghi S; XIIth Stroke Treatment Academic Industry Roundtable. Most Promising Approaches to Improve Stroke Outcomes: The Stroke Treatment Academic Industry Roundtable XII Workshop. Stroke. 2023 Dec;54(12):3202-3213. doi: 10.1161/STROKEAHA.123.044279. Epub 2023 Oct 27.

  PMID: 37886850 BACKGROUND

• Tu WJ, Zhao Z, Yin P, Cao L, Zeng J, Chen H, Fan D, Fang Q, Gao P, Gu Y, Tan G, Han J, He L, Hu B, Hua Y, Kang D, Li H, Liu J, Liu Y, Lou M, Luo B, Pan S, Peng B, Ren L, Wang L, Wu J, Xu Y, Xu Y, Yang Y, Zhang M, Zhang S, Zhu L, Zhu Y, Li Z, Chu L, An X, Wang L, Yin M, Li M, Yin L, Yan W, Li C, Tang J, Zhou M, Wang L. Estimated Burden of Stroke in China in 2020. JAMA Netw Open. 2023 Mar 1;6(3):e231455. doi: 10.1001/jamanetworkopen.2023.1455.

  PMID: 36862407 BACKGROUND

• Hu S, Cui B, Mlynash M, Zhang X, Mehta KM, Lansberg MG. Stroke epidemiology and stroke policies in China from 1980 to 2017: A systematic review and meta-analysis. Int J Stroke. 2020 Jan;15(1):18-28. doi: 10.1177/1747493019873562. Epub 2019 Sep 22.

  PMID: 31543073 BACKGROUND

• Wang YJ, Li ZX, Gu HQ, Zhai Y, Zhou Q, Jiang Y, Zhao XQ, Wang YL, Yang X, Wang CJ, Meng X, Li H, Liu LP, Jing J, Wu J, Xu AD, Dong Q, Wang D, Wang WZ, Ma XD, Zhao JZ; China Stroke Statistics Writing Committee. China Stroke Statistics: an update on the 2019 report from the National Center for Healthcare Quality Management in Neurological Diseases, China National Clinical Research Center for Neurological Diseases, the Chinese Stroke Association, National Center for Chronic and Non-communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention and Institute for Global Neuroscience and Stroke Collaborations. Stroke Vasc Neurol. 2022 Oct;7(5):415-450. doi: 10.1136/svn-2021-001374. Epub 2022 Apr 20.

  PMID: 35443985 BACKGROUND

• Wang L, Zhou B, Zhao Z, Yang L, Zhang M, Jiang Y, Li Y, Zhou M, Wang L, Huang Z, Zhang X, Zhao L, Yu D, Li C, Ezzati M, Chen Z, Wu J, Ding G, Li X. Body-mass index and obesity in urban and rural China: findings from consecutive nationally representative surveys during 2004-18. Lancet. 2021 Jul 3;398(10294):53-63. doi: 10.1016/S0140-6736(21)00798-4.

  PMID: 34217401 BACKGROUND

• Wang L, Peng W, Zhao Z, Zhang M, Shi Z, Song Z, Zhang X, Li C, Huang Z, Sun X, Wang L, Zhou M, Wu J, Wang Y. Prevalence and Treatment of Diabetes in China, 2013-2018. JAMA. 2021 Dec 28;326(24):2498-2506. doi: 10.1001/jama.2021.22208.

  PMID: 34962526 BACKGROUND

• Owolabi MO, Thrift AG, Mahal A, Ishida M, Martins S, Johnson WD, Pandian J, Abd-Allah F, Yaria J, Phan HT, Roth G, Gall SL, Beare R, Phan TG, Mikulik R, Akinyemi RO, Norrving B, Brainin M, Feigin VL; Stroke Experts Collaboration Group. Primary stroke prevention worldwide: translating evidence into action. Lancet Public Health. 2022 Jan;7(1):e74-e85. doi: 10.1016/S2468-2667(21)00230-9. Epub 2021 Oct 29.

  PMID: 34756176 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke

Interventions

Vitamin K 2

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Vitamin K; Naphthoquinones; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Phytol; Diterpenes; Terpenes; Quinones; Polycyclic Compounds

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 14, 2025
• First Posted: February 10, 2025
• Study Start: March 23, 2025
• Primary Completion (Estimated): January 15, 2027
• Study Completion (Estimated): January 31, 2028
• Last Updated: March 3, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

CN (3)