Rehabilomics Study in Stroke Patients After Robotic Rehabilitation

NCT04223180 | Completed

• 1 other identifier: FDG_EPIGEN_2019
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Stroke is associated with disability and impaired quality of life. Persistent motor impairment is common with incomplete recovery of motor function after rehabilitation, mainly in the upper limbs (UL). Robot-mediated therapy (RMT) has been proposed as a viable approach for the rehabilitation of the UL, but more rigorous studies are needed to tailor rehabilitation and to better address the treatment. Brain-derived neurotrophic factor (BDNF) and the serotonin transporter gene (SLC6A4) have been shown to play an important role in post-stroke recovery. After ischemic stroke, disruption and subsequent reorganization of functional brain connections occur both locally and far from the lesion, with the latter possibly contributing to function recovery. This project aims to assess whether epigenetic and genetic variations of BDNF and SLC6A4 can occur in stroke patients after robotic rehabilitation treatment. This study will allow to identify potential genetic and epigenetic biomarkers in post-stroke rehabilitation that could be used to predict the response to a specific rehabilitation treatment and to choose the optimal treatment for the patient (Rehabilomics).

Conditions

Stroke

Keywords

Rehabilitation; Upper Limb; Methylation; Single nucleotide polymorphism; BDNF; SLC6A4; Rehabilomics

Outcome Measures

Primary Outcomes (2)

• Presence/absence of rs6265 in the BDNF

  BDNF rs6265 polymorphism will be analyzed using HpyCH4IV restriction enzyme which identifies homozygous Valine/Valine, heterozygous Valine/Methionine and homozygous Methionine/Methionine

  Baseline (T0)

• Presence/absence of 5-HTTLPR in the SLC6A4

  SLC6A4 5-HTTLPR polymorphism will be analyzed by a specific protocol that identifies gene polymorphisms according to the polymerase chain reaction (PCR) fragment sizes: short \[S; 486 base pairs (bp), 14 repeats\], long \[L; 529bp, 16 repeats\], or extra-long \[XL; 612 or 654bp, 20 or 22 repeats\].

  Baseline (T0)

Secondary Outcomes (2)

• Change in promoter methylation levels of BDNF gene

  Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

• Change in promoter methylation levels of SLC6A4 gene

  Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Other Outcomes (9)

• Change in Fugl-Meyer Assessment of Motor Recovery after Stroke for Upper Extremity portion (FMA-UL)

  Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

• Change in Modified Barthel Index (BI)

  Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

• Change in Motricity Index (MI)

  Baseline [T0], First Treatment (6 weeks and 30 rehabilitation session) [T1], Second treatment (other 6 weeks and other 30 rehabilitation session) [T2]

Study Arms (1)

Stroke patients

Inpatients and outpatients admitted to the investigators' rehabilitation facility with an upper limb impairment due to neurologic or orthopedic disorders.

Device: Robotic assisted intervention

Interventions

Robotic assisted intervention DEVICE

Robotic treatment of the upper limb (30 sessions, 5 times a week) using a set of 4 robotic devices: Motore (Humanware); Amadeo, Diego, Pablo (Tyromotion). The training will include motor-cognitive exercises specifically selected to train spatial attention, vision and working memory, praxis, executive function, and speed of processing.

Stroke patients

Eligibility Criteria

• Age: 55 Years - 85 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The investigators will enroll both inpatients and outpatients admitted to their rehabilitation facility with an upper limb impairment due to neurologic or orthopedic disorders.

You may qualify if:

• sub-acute patients, with ischemic or hemorrhagic stroke, documented by MRI or CT;
• age between 55 and 85 years;
• patients able to perform a rehabilitation treatment focused on the UL, for at least 45 min/day, for 5 days/week;
• time latency since stroke ranging from 2 weeks to 6 months,
• cognitive and language abilities sufficient to understand the experiments and follow instructions.

You may not qualify if:

• a previous stroke;
• behavioral and cognitive disorders and/or reduced compliance interfering with active therapy;
• fixed contraction deformity in the affected limb interfering with active therapy (ankylosis, Modified Ashworth Scale = 4);
• severe deficits in visual acuity;
• upper extremity Fugl-Meyer score \>58.

Sponsors & Collaborators

• Fondazione Don Carlo Gnocchi Onlus: lead

Study Sites (1)

Don carlo Gnocchi Foundation

Roma, 00168, Italy

Location

Related Publications (12)

• Krakauer JW. Arm function after stroke: from physiology to recovery. Semin Neurol. 2005 Dec;25(4):384-95. doi: 10.1055/s-2005-923533.

  PMID: 16341995 BACKGROUND

• Kelly-Hayes M, Beiser A, Kase CS, Scaramucci A, D'Agostino RB, Wolf PA. The influence of gender and age on disability following ischemic stroke: the Framingham study. J Stroke Cerebrovasc Dis. 2003 May-Jun;12(3):119-26. doi: 10.1016/S1052-3057(03)00042-9.

  PMID: 17903915 BACKGROUND

• Prabhakaran S, Zarahn E, Riley C, Speizer A, Chong JY, Lazar RM, Marshall RS, Krakauer JW. Inter-individual variability in the capacity for motor recovery after ischemic stroke. Neurorehabil Neural Repair. 2008 Jan-Feb;22(1):64-71. doi: 10.1177/1545968307305302. Epub 2007 Aug 8.

  PMID: 17687024 BACKGROUND

• Pearson-Fuhrhop KM, Burke E, Cramer SC. The influence of genetic factors on brain plasticity and recovery after neural injury. Curr Opin Neurol. 2012 Dec;25(6):682-8. doi: 10.1097/WCO.0b013e32835a360a.

  PMID: 23044515 BACKGROUND

• Lindgren A. Stroke genetics: a review and update. J Stroke. 2014 Sep;16(3):114-23. doi: 10.5853/jos.2014.16.3.114. Epub 2014 Sep 30.

  PMID: 25328870 BACKGROUND

• Shiner CT, Pierce KD, Thompson-Butel AG, Trinh T, Schofield PR, McNulty PA. BDNF Genotype Interacts with Motor Function to Influence Rehabilitation Responsiveness Poststroke. Front Neurol. 2016 May 17;7:69. doi: 10.3389/fneur.2016.00069. eCollection 2016.

  PMID: 27242654 BACKGROUND

• Stanne TM, Tjarnlund-Wolf A, Olsson S, Jood K, Blomstrand C, Jern C. Genetic variation at the BDNF locus: evidence for association with long-term outcome after ischemic stroke. PLoS One. 2014 Dec 3;9(12):e114156. doi: 10.1371/journal.pone.0114156. eCollection 2014.

  PMID: 25470006 BACKGROUND

• Kim JM, Stewart R, Kang HJ, Kim SW, Shin IS, Kim HR, Shin MG, Kim JT, Park MS, Cho KH, Yoon JS. A longitudinal study of SLC6A4 DNA promoter methylation and poststroke depression. J Psychiatr Res. 2013 Sep;47(9):1222-7. doi: 10.1016/j.jpsychires.2013.04.010. Epub 2013 May 20.

  PMID: 23702251 BACKGROUND

• Santoro M, Fontana L, Masciullo M, Bianchi ML, Rossi S, Leoncini E, Novelli G, Botta A, Silvestri G. Expansion size and presence of CCG/CTC/CGG sequence interruptions in the expanded CTG array are independently associated to hypermethylation at the DMPK locus in myotonic dystrophy type 1 (DM1). Biochim Biophys Acta. 2015 Dec;1852(12):2645-52. doi: 10.1016/j.bbadis.2015.09.007. Epub 2015 Sep 21. No abstract available.

  PMID: 26391753 BACKGROUND

• Nociti V, Santoro M, Quaranta D, Losavio FA, De Fino C, Giordano R, Palomba NP, Rossini PM, Guerini FR, Clerici M, Caputo D, Mirabella M. BDNF rs6265 polymorphism methylation in Multiple Sclerosis: A possible marker of disease progression. PLoS One. 2018 Oct 23;13(10):e0206140. doi: 10.1371/journal.pone.0206140. eCollection 2018.

  PMID: 30352103 BACKGROUND

• Aprile I, Germanotta M, Cruciani A, Loreti S, Pecchioli C, Cecchi F, Montesano A, Galeri S, Diverio M, Falsini C, Speranza G, Langone E, Papadopoulou D, Padua L, Carrozza MC; FDG Robotic Rehabilitation Group. Upper Limb Robotic Rehabilitation After Stroke: A Multicenter, Randomized Clinical Trial. J Neurol Phys Ther. 2020 Jan;44(1):3-14. doi: 10.1097/NPT.0000000000000295.

  PMID: 31834217 BACKGROUND

• Aprile I, Cruciani A, Germanotta M, Gower V, Pecchioli C, Cattaneo D, Vannetti F, Padua L, Gramatica F. Upper Limb Robotics in Rehabilitation: An Approach to Select the Devices, Based on Rehabilitation Aims, and Their Evaluation in a Feasibility Study. Applied Sciences 9(18): 3920; 2019. https://doi.org/10.3390/app9183920

  BACKGROUND

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

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

Study Officials

• Irene Aprile, MD, PhD

  IRCCS Fondazione Don Carlo Gnocchi

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: January 10, 2020
• Study Start: January 20, 2020
• Primary Completion: January 31, 2021
• Study Completion: January 31, 2021
• Last Updated: February 23, 2021

Record last verified: 2019-12

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)