Clinical trial NCT05648422: Effect of the Nutritional Support System on Neuromotor Alterations in Patients With Cerebral Palsy
Official title: Effect of the Nutritional Support System (NSS) on Neuromotor Alterations in Patients With Cerebral Palsy
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Cerebral Palsy
Spastic
Malnutrition
Keywords: Cerebral Palsy
Nutritional Support
NSS
Probiotics
Diet
Neurogenesis
Neuroplasticity
Lead sponsor: Anahuac University
Sponsor class: OTHER
First posted: 2022-12-13
Enrollment: 144
Sex: ALL
Minimum age (years): 4
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Intervention model description: Randomized, controlled clinical trial with blinding.
Primary purpose: TREATMENT

Brief summary: Study to determine the impact of a nutritional support system (NSS) on neuromotor alterations in patients with cerebral palsy.

Detailed description: Cerebral Palsy (CP) is a group of motor disorders of the brain and can be accompanied by alterations in sensation, perception, cognition, communication and behavior, epilepsy and secondary musculoskeletal disorders. These disorders decrease daily functional performance in the areas of mobility, cognition and self-care, resulting in the need for a primary caregiver and increased health care costs. Rehabilitative treatment to increase functional independence is taken from the point of view of motor function (physiotherapy), however, no emphasis is placed on nutritional treatment aimed at alterations in mobility, cognition and self-care; currently it has been observed that eating disorders alter neuromuscular function directly or indirectly, therefore many patients do not respond adequately to treatment due to deterioration in secondary nutritional status. Dietary deficiency in patients with ICH is the result of the lack of an essential nutrient in the diet, each of these nutrients has a functional dynamic in the different stages, so that if one of them is missing or deficient, a functional or organic alteration, a biochemical variation or a disorder in body mass will occur. The World Health Organization (WHO) only considers energy, protein and fat requirements according to the age of the child. The NSS (Nutritional Support System) consisting of specific diet, supplementation (glutamine, arginine, folic acid, PUFA-n3, vegetal protein, nicotinic acid, cobalamin, thiamine, pyridoxine, magnesium, zinc, selenium, cholecalciferol, resveratrol, ascorbic acid, Spirulina Máxima, and inuline) and probiotics, have individually demonstrated effects such as neuronal regeneration, neuroprotective effect, reduction of oxidative stress.

A randomized, blinded, clinical trial will be conducted in children aged 4 to 11 years with CP functional level III of the Gross Motor Function Classification System (GMFCS), without impaired cognitive status and unable to walk on their own. They are randomly assigned to three groups: 1) follow-up group (GS) to which conventional diet (WHO) be applied; 2) control group 2 (GC) to which conventional diet (WHO), deworming and probiotics will be applied 3) intervention group (GI) deworming, probiotics, NSS supplements and specific diet will be applied, they will be followed up for three months; They will be evaluated at baseline, week 7 and week 13 with Gross Motor Function Measure 66 (GMFM-66) and MACS; at baseline and week 13 with kinetics and kinematic analysis, and electromyography (EMG). Statistical analysis: For the intragroup inferential statistical analysis, 2-way ANOVA will be used if the distribution is normal, otherwise FRIEDMAN will be used, in both cases post hoc tests will be applied; for the intergroup analysis, 1-way ANOVA will be used if the distribution is normal, otherwise KRUSKAL WALLIS will be used, in both cases post hoc tests will be applied.

Eligibility criteria: Inclusion Criteria:

* Patients with GMFCS III classification.
* Patients with spastic CP.
* Both sexes age 4 to 11 years.
* Primary caregiver engaged (full presence).
* Able to follow instructions.
* Tolerant to oral feeding.
* Parents or guardians to sign informed consent letter.
* Children, if able to write, sign the letter of assent.

Exclusion Criteria:

* Have received antibiotics 15 days prior to treatment.
* Having received botulinum toxin therapy in the last six months. Consumption of muscle relaxants in the last three months.
* Patient with any type of surgery in a period of less than 6 months.
* Presence of any other catabolic disease, which further increases their risk of malnutrition (renal, cardiovascular, pulmonary, hepatic, immunological).
* Intolerance to oral feeding.
* Lack of stimulation at home.
* Moderate to severe gastroesophageal reflux.
* Able to walk without support.

Primary outcomes:
measure: CHANGE FROM BASELINE GROSS MOTOR FUNCTION MEASURE 66 AT 7 WEEKS
timeFrame: Baseline period, and week 7
measure: CHANGE FROM BASELINE GROSS MOTOR FUNCTION MEASURE 66 AT 13 WEEKS
timeFrame: Baseline period, and week 13
measure: CHANGE FROM BASELINE MANUAL ABILITY CLASSIFICATION SYSTEM AT 7 WEEKS
timeFrame: Baseline period, week 7
measure: CHANGE FROM BASELINE MANUAL ABILITY CLASSIFICATION SYSTEM 13 WEEKS
timeFrame: Baseline period, week 13
measure: CHANGE FROM BASELINE MUSCLE ELECTRIC ACTIVITY AT 13 WEEKS
timeFrame: Baseline and week 13
measure: CHANGE FROM BASELINE GAIT ANALYSIS AT 13 WEEKS
timeFrame: Baseline and week 13
measure: CHANGE FROM BASELINE CRAWLING ANALYSIS AT 13 WEEKS
timeFrame: Baseline and week 13
Secondary outcomes:
measure: CHANGE FROM BASELINE MIDARM MUSCLE AREA AT 7 WEEKS
timeFrame: Baseline and week 7
measure: CHANGE FROM BASELINE MIDARM MUSCLE AREA AT 13 WEEKS
timeFrame: Baseline and week 13
Other outcomes:
Locations:
city: Mexico
country: Mexico
facility: Apac I.A.P. (Association For People With Cerebral Palsy)
Study officials:
affiliation: Anahuac University
name: Fernando Leal, PhD
role: STUDY_DIRECTOR
References:
citation: Trotta T, Porro C, Cianciulli A, Panaro MA. Beneficial Effects of Spirulina Consumption on Brain Health. Nutrients. 2022 Feb 5;14(3):676. doi: 10.3390/nu14030676.
citation: Schweizer U, Fabiano M. Selenoproteins in brain development and function. Free Radic Biol Med. 2022 Sep;190:105-115. doi: 10.1016/j.freeradbiomed.2022.07.022. Epub 2022 Aug 10.
citation: Roy Sarkar S, Mitra Mazumder P, Chatterjee K, Sarkar A, Adhikary M, Mukhopadhyay K, Banerjee S. Saccharomyces boulardii ameliorates gut dysbiosis associated cognitive decline. Physiol Behav. 2021 Jul 1;236:113411. doi: 10.1016/j.physbeh.2021.113411. Epub 2021 Mar 31.
citation: Visco DB, Toscano AE, Juarez PAR, Gouveia HJCB, Guzman-Quevedo O, Torner L, Manhaes-de-Castro R. A systematic review of neurogenesis in animal models of early brain damage: Implications for cerebral palsy. Exp Neurol. 2021 Jun;340:113643. doi: 10.1016/j.expneurol.2021.113643. Epub 2021 Feb 23.
citation: Rubin DI. Needle Electromyography Waveforms During Needle Electromyography. Neurol Clin. 2021 Nov;39(4):919-938. doi: 10.1016/j.ncl.2021.06.003. Epub 2021 Aug 31.
citation: Le Roy C, Barja S, Sepulveda C, Guzman ML, Olivarez M, Figueroa MJ, Alvarez M. Vitamin D and iron deficiencies in children and adolescents with cerebral palsy. Neurologia (Engl Ed). 2021 Mar;36(2):112-118. doi: 10.1016/j.nrl.2017.11.005. Epub 2018 Jan 17. English, Spanish.
citation: Tinkov AA, Skalnaya MG, Skalny AV. Serum trace element and amino acid profile in children with cerebral palsy. J Trace Elem Med Biol. 2021 Mar;64:126685. doi: 10.1016/j.jtemb.2020.126685. Epub 2020 Nov 12.
citation: Huff TC, Sant DW, Camarena V, Van Booven D, Andrade NS, Mustafi S, Monje PV, Wang G. Vitamin C regulates Schwann cell myelination by promoting DNA demethylation of pro-myelinating genes. J Neurochem. 2021 Jun;157(6):1759-1773. doi: 10.1111/jnc.15015. Epub 2020 Apr 14.
citation: Sorrenti V, Castagna DA, Fortinguerra S, Buriani A, Scapagnini G, Willcox DC. Spirulina Microalgae and Brain Health: A Scoping Review of Experimental and Clinical Evidence. Mar Drugs. 2021 May 22;19(6):293. doi: 10.3390/md19060293.
citation: Eyles DW. Vitamin D: Brain and Behavior. JBMR Plus. 2020 Oct 18;5(1):e10419. doi: 10.1002/jbm4.10419. eCollection 2021 Jan.
citation: Kazmierczak-Siedlecka K, Ruszkowski J, Fic M, Folwarski M, Makarewicz W. Saccharomyces boulardii CNCM I-745: A Non-bacterial Microorganism Used as Probiotic Agent in Supporting Treatment of Selected Diseases. Curr Microbiol. 2020 Sep;77(9):1987-1996. doi: 10.1007/s00284-020-02053-9. Epub 2020 May 29.
citation: Sainz-Pelayo MP, Albu S, Murillo N, Benito-Penalva J. [Spasticity in neurological pathologies. An update on the pathophysiological mechanisms, advances in diagnosis and treatment]. Rev Neurol. 2020 Jun 16;70(12):453-460. doi: 10.33588/rn.7012.2019474. Spanish.
citation: Sadowska M, Sarecka-Hujar B, Kopyta I. Cerebral Palsy: Current Opinions on Definition, Epidemiology, Risk Factors, Classification and Treatment Options. Neuropsychiatr Dis Treat. 2020 Jun 12;16:1505-1518. doi: 10.2147/NDT.S235165. eCollection 2020.
citation: Vitrikas K, Dalton H, Breish D. Cerebral Palsy: An Overview. Am Fam Physician. 2020 Feb 15;101(4):213-220.
citation: Leal-Martinez F, Franco D, Pena-Ruiz A, Castro-Silva F, Escudero-Espinosa AA, Rolon-Lacarrier OG, Lopez-Alarcon M, De Leon X, Linares-Eslava M, Ibarra A. Effect of a Nutritional Support System (Diet and Supplements) for Improving Gross Motor Function in Cerebral Palsy: An Exploratory Randomized Controlled Clinical Trial. Foods. 2020 Oct 13;9(10):1449. doi: 10.3390/foods9101449.
citation: Choi S, Hong DK, Choi BY, Suh SW. Zinc in the Brain: Friend or Foe? Int J Mol Sci. 2020 Nov 25;21(23):8941. doi: 10.3390/ijms21238941.
citation: Santos HO, Teixeira FJ, Schoenfeld BJ. Dietary vs. pharmacological doses of zinc: A clinical review. Clin Nutr. 2020 May;39(5):1345-1353. doi: 10.1016/j.clnu.2019.06.024. Epub 2019 Jul 4.
citation: Hariharan S, Dharmaraj S. Selenium and selenoproteins: it's role in regulation of inflammation. Inflammopharmacology. 2020 Jun;28(3):667-695. doi: 10.1007/s10787-020-00690-x. Epub 2020 Mar 6.
citation: Calderon-Ospina CA, Nava-Mesa MO. B Vitamins in the nervous system: Current knowledge of the biochemical modes of action and synergies of thiamine, pyridoxine, and cobalamin. CNS Neurosci Ther. 2020 Jan;26(1):5-13. doi: 10.1111/cns.13207. Epub 2019 Sep 6.
citation: Michielsen M, Vaughan-Graham J, Holland A, Magri A, Suzuki M. The Bobath concept - a model to illustrate clinical practice. Disabil Rehabil. 2019 Aug;41(17):2080-2092. doi: 10.1080/09638288.2017.1417496. Epub 2017 Dec 17.
citation: Vinals-Labanino CP, Velazquez-Bustamante AE, Vargas-Santiago SI, Arenas-Sordo ML. Usefulness of Cerebral Palsy Curves in Mexican Patients: A Cross-Sectional Study. J Child Neurol. 2019 May;34(6):332-338. doi: 10.1177/0883073819830560. Epub 2019 Mar 11.
citation: Fragale N, Navarre N, Rogers J. General Nutrition for Children with Cerebral Palsy. In: Miller F, Bachrach S, Lennon N, O'Neil M, editors. Cerebral Palsy Cham: Springer International Publishing; 2019. p. 1-10.
citation: Steele KM, Munger ME, Peters KM, Shuman BR, Schwartz MH. Repeatability of electromyography recordings and muscle synergies during gait among children with cerebral palsy. Gait Posture. 2019 Jan;67:290-295. doi: 10.1016/j.gaitpost.2018.10.009. Epub 2018 Oct 22.
citation: Picon-Pages P, Garcia-Buendia J, Munoz FJ. Functions and dysfunctions of nitric oxide in brain. Biochim Biophys Acta Mol Basis Dis. 2019 Aug 1;1865(8):1949-1967. doi: 10.1016/j.bbadis.2018.11.007. Epub 2018 Nov 27.
citation: Kaur H, Bose C, Mande SS. Tryptophan Metabolism by Gut Microbiome and Gut-Brain-Axis: An in silico Analysis. Front Neurosci. 2019 Dec 18;13:1365. doi: 10.3389/fnins.2019.01365. eCollection 2019.
citation: Lu J, Claud EC. Connection between gut microbiome and brain development in preterm infants. Dev Psychobiol. 2019 Jul;61(5):739-751. doi: 10.1002/dev.21806. Epub 2018 Nov 20.
citation: Panti-May JA, Zonta ML, Cociancic P, Barrientos-Medina RC, Machain-Williams C, Robles MR, Hernandez-Betancourt SF. Occurrence of intestinal parasites in Mayan children from Yucatan, Mexico. Acta Trop. 2019 Jul;195:58-61. doi: 10.1016/j.actatropica.2019.04.023. Epub 2019 Apr 22.
citation: Bivona G, Gambino CM, Iacolino G, Ciaccio M. Vitamin D and the nervous system. Neurol Res. 2019 Sep;41(9):827-835. doi: 10.1080/01616412.2019.1622872. Epub 2019 May 30.
citation: Gasperi V, Sibilano M, Savini I, Catani MV. Niacin in the Central Nervous System: An Update of Biological Aspects and Clinical Applications. Int J Mol Sci. 2019 Feb 23;20(4):974. doi: 10.3390/ijms20040974.
citation: Ballaz SJ, Rebec GV. Neurobiology of vitamin C: Expanding the focus from antioxidant to endogenous neuromodulator. Pharmacol Res. 2019 Aug;146:104321. doi: 10.1016/j.phrs.2019.104321. Epub 2019 Jun 20.
citation: Heshmati J, Morvaridzadeh M, Maroufizadeh S, Akbari A, Yavari M, Amirinejad A, Maleki-Hajiagha A, Sepidarkish M. Omega-3 fatty acids supplementation and oxidative stress parameters: A systematic review and meta-analysis of clinical trials. Pharmacol Res. 2019 Nov;149:104462. doi: 10.1016/j.phrs.2019.104462. Epub 2019 Sep 26.
citation: Tamtaji OR, Heidari-Soureshjani R, Mirhosseini N, Kouchaki E, Bahmani F, Aghadavod E, Tajabadi-Ebrahimi M, Asemi Z. Probiotic and selenium co-supplementation, and the effects on clinical, metabolic and genetic status in Alzheimer's disease: A randomized, double-blind, controlled trial. Clin Nutr. 2019 Dec;38(6):2569-2575. doi: 10.1016/j.clnu.2018.11.034. Epub 2018 Dec 10.
citation: Sharma SK, Bansal MP, Sandhir R. Altered dietary selenium influences brain iron content and behavioural outcomes. Behav Brain Res. 2019 Oct 17;372:112011. doi: 10.1016/j.bbr.2019.112011. Epub 2019 Jun 15.
citation: Gao Z, Chen L, Xiong Q, Xiao N, Jiang W, Liu Y, Wu X, Hou W. Degraded Synergistic Recruitment of sEMG Oscillations for Cerebral Palsy Infants Crawling. Front Neurol. 2018 Sep 18;9:760. doi: 10.3389/fneur.2018.00760. eCollection 2018.
citation: Caramico-Favero DCO, Guedes ZCF, Morais MB. FOOD INTAKE, NUTRITIONAL STATUS AND GASTROINTESTINAL SYMPTOMS IN CHILDREN WITH CEREBRAL PALSY. Arq Gastroenterol. 2018 Oct-Dec;55(4):352-357. doi: 10.1590/S0004-2803.201800000-78.
citation: Guo YE, Suo N, Cui X, Yuan Q, Xie X. Vitamin C promotes oligodendrocytes generation and remyelination. Glia. 2018 Jul;66(7):1302-1316. doi: 10.1002/glia.23306. Epub 2018 Feb 9.
citation: Garcia-Sanchez SF, Gomez-Galindo MT, Guzman-Pantoja JE. [Botulinum toxin A and physical therapy in gait in cerebral palsy]. Rev Med Inst Mex Seguro Soc. 2017 Jan-Feb;55(1):18-24. Spanish.
citation: Westfall S, Lomis N, Kahouli I, Dia SY, Singh SP, Prakash S. Microbiome, probiotics and neurodegenerative diseases: deciphering the gut brain axis. Cell Mol Life Sci. 2017 Oct;74(20):3769-3787. doi: 10.1007/s00018-017-2550-9. Epub 2017 Jun 22.