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StrokeNCT04223180

Rehabilomics Study in Stroke Patients After Robotic Rehabilitation

An observational study of Stroke, run by Fondazione Don Carlo Gnocchi ETS at 1 site in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 55 to 85 years
Conditions the study is for
Stroke
What is being tested?
Robotic assisted intervention
Type of treatment
Medical device
How many people
50 participants
Where
1 siteItaly
Study dates
20 Jan 2020to 31 Jan 2021
Phase
Observational
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 55 to 85 years
  • All sexes
  • Adult, Older adult

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.

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

1 site in 1 country.

Italy1 site

  • Don carlo Gnocchi Foundation

    Roma, 00168

Other trials in Italy

About this study

Official title: Stroke Rehabilomics Study: Epigenetics and Genetics Characterization of the BDNF and SLC6A4 Genes in Patients Undergoing Robotic Rehabilitation Treatment

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).

Read the detailed description

Epigenetic and single-nucleotide polymorphisms (SNPs) in genes may influence an individual's capacity for use-dependent plasticity, and hence their responsiveness to post-stroke rehabilitation. Understanding genetic variation gives clinicians a biological signal that could be used to predict who is most likely to recover from neural injury, to choose the optimal treatment for a patient, or to supplement rehabilitation therapy.

Robotics demonstrated to be an effective rehabilitation treatment for functional and motor recovery after stroke and, on the basis of investigators' preliminary results, it seems to be an useful therapy to improve some cognitive functions. The identification of individual characteristics is crucial factor to better address this treatment and to develop more tailored patients' rehabilitation program.

The characterization of the link between personal biology and rehabilitation treatment response will allow to define a model of Rehabilomics research as a translational framework for programs of precision rehabilitation and intervention research.

In order to identify potential diagnostic and prognostic genetic biomarkers in post-stroke rehabilitation, the investigators will analyze the promoter methylation of BDNF and SLC6A4, two genes implicated in sub-acute stroke recovery. Moreover, the investigators will also detect BDNF rs6265 and SLC6A4 5-HTTLPR polymorphisms.

Subjects will be evaluated at baseline (T0), after 30 sessions of rehabilitation treatment (T1) and, if possible, after other 30 sessions of rehabilitation treatment from T1 (T2).

All patients will perform a robotic treatment of the upper limb (30 sessions, 5 times a week) using a set of robotic devices. Where possible, some patients will undergo further 30 robotic rehabilitation sessions after T1.

Peripheral blood (6ml) will be taken from all subjects at three time points (T0, T1 and T2) during the rehabilitation treatment.

Genomic DNA, obtained from peripheral blood will be analyzed to evaluate promoter methylation of BDNF and SLC6A4 using pyrosequencing analysis with PyroMark Q24 (Qiagen, Germany).

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

For the SLC6A4 5-HTTLPR polymorphism, the investigators will follow 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].

Genetic and epigenetic results will be correlated with:

  1. the effects of the robotic rehabilitation on the upper limb function and disability measured with the following clinical scales: Fugl-Meyer Assessment for Upper Extremity (FMA), to evaluate motor function; the Motricity Index (MI), to evaluate muscle strength; the Modified Barthel Index (mBI), to evaluate activities of daily living (ADL) and mobility. ii) the effects on cognitive functions measured with following cognitive tests: 1) Digit Span (attention/short-term memory involving strings/series of digits of varying length); 2) Tower of London (planning and problem solving); 3) STROOP test (Stroop Color and Word Test); 4) Symbol Digit Modalities Test (processing speed of visual stimuli); 5) Rey-Osterrieth Complex Figure Test (ROCF) (visuomotor integration).
Conditions
Stroke
Being tested
Robotic assisted intervention
Keywords
Rehabilitation, Upper Limb, Methylation, Single nucleotide polymorphism, BDNF, SLC6A4, Rehabilomics
Medical subject headings
Stroke

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Robotic assisted interventionDevice

    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.

Study groups in NCT04223180
Study groupRoleWhat they receive
Stroke patientsInpatients and outpatients admitted to the investigators' rehabilitation facility with an upper limb impairment due to neurologic or orthopedic disorders.
Receives: Device: Robotic assisted intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Baseline (T0)

  2. 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].

    Measured: Baseline (T0)

Secondary outcomes (2)

  1. Change in promoter methylation levels of BDNF gene

    Promoter methylation of BDNF using pyrosequencing analysis with PyroMark Q24 (Qiagen, Germany).

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

  2. Change in promoter methylation levels of SLC6A4 gene

    Promoter methylation of SLC6A4 using pyrosequencing analysis with PyroMark Q24 (Qiagen, Germany).

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Jan 2020
  2. Study start20 Jan 2020
  3. Primary completion31 Jan 2021
  4. Study completion31 Jan 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Observational
Observational model
Cohort
Time perspective
Prospective
Enrolment
50 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04223180
Sponsor's protocol ID
FDG_EPIGEN_2019
Status last verified
Dec 2019
First submitted
20 Dec 2019
Last updated
23 Feb 2021
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

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

    PubMed 16341995

  • 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.

    PubMed 17903915

  • 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.

    PubMed 17687024

  • 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.

    PubMed 23044515

  • 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.

    PubMed 25328870

  • 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.

    PubMed 27242654

  • 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.

    PubMed 25470006

  • 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.

    PubMed 23702251

  • 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.

    PubMed 26391753

  • 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.

    PubMed 30352103

  • 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.

    PubMed 31834217

  • 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

Questions about this trial

What is this clinical trial studying?

An observational study of Stroke, run by Fondazione Don Carlo Gnocchi ETS at 1 site in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Presence/absence of rs6265 in the BDNF (time frame: Baseline (T0)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04223180, which also lists 12 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Feb 2021.

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