Clinical trial NCT06267222: Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia
Official title: Trans-spinal Electrical Stimulation in Individuals With Spinocerebellar Ataxia: a Pragmatic Study
Study type: INTERVENTIONAL
Overall status: ENROLLING_BY_INVITATION
Phase: NA
Conditions: SCA
Postural Balance
Gait Ataxia
Keywords: NIBS
TRANS-SPINAL STIMULATION
CEREBELLAR ATAXIA
Lead sponsor: Centro Universitário Augusto Motta
Sponsor class: OTHER
Collaborators: name: Federal Institute of Rio de Janeiro
First posted: 2024-02-20
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: This is a pragmatic clinical trial that will be carried out using the CONSORT-Pragmatic Trials (Zwarenstein et al., 2008).
Primary purpose: TREATMENT

Brief summary: The main goal of this pragmatic clinical trial is to investigate the effects of trans-spinal tDCS in individuals with spinocerebellar ataxia (SCA) over some parameters of gait and postural control in real-world conditions, reflecting daily clinical practice. The main questions it aims to answer are:

* If an extended number of tDCS sessions, beyond the typical 5 to 10 sessions described in scientific literature, applied concomitantly with exercises with progressive challenges, to yield positive outcomes over some parameters of gait and postural control in individuals with SCA and if there is retention of possible benefits one month later the end of this protocol.
* If there is specific characteristics (including balance, gait, mobility, severity of ataxia, DNA test characteristics and non-ataxic signs) in individuals with SCA that can predict their improvement in postural control and gait following the 20 tDCS sessions.

  * Participants will receive 20 tDCS sessions concomitantly with exercises for gait and postural control with progressive challenges.
  * Postural control and gait of the participants will be assessed in two big sessions before (#assessment 1) and after the 20 sessions (#assessment 5) and 3 small sessions after every 5 sessions (#assessments 2, 3 and 4). Also, as a follow-up, they will be assessed a month after the end of the intervention (#assessment 6).

Detailed description: Spinocerebellar ataxias (SCA) comprise a group of progressive degenerative diseases, currently lacking pharmacological treatments. These conditions produce gait and balance disorders, ultimately necessitating the use of assistive devices, culminating in wheelchair dependency upon the loss of ambulatory function during the clinical progression of SCA. This significantly impacts the individual's independence and quality of life. Recent clinical trials have demonstrated that the application of transcranial direct current stimulation (tDCS) over the cerebellum and spinal cord (trans-spinal stimulation) has led to improvements in upper limb coordination, gait ataxia severity, motor scores (including balance), cognitive abilities, and quality of life in individuals with degenerative ataxias, including SCA. However, it is not yet known whether all patients with SCA demonstrate significant improvement with this intervention. Moreover, if there is no improvement, it remains unclear whether specific characteristics of individuals with SCA, such as balance, gait, mobility, ataxia severity, DNA test results, and non-ataxic signs, can be identified to predict their response to tDCS sessions. Additionally, tDCS studies in individuals with SCA typically involve 5 to 10 stimulation sessions without associating stimulation with exercises of progressive difficulty. One of the main benefits of using tDCS is the plastic modulation of the nervous system. Therefore, the lack of challenges concomitant with the use of tDCS limits its results. Aim: The main goal of this pragmatic clinical trial is to investigate the effects of trans-spinal tDCS in individuals with SCA over some parameters of gait and postural control in real-world conditions, reflecting daily clinical practice. The specific aims of this study are: (i) Determine whether particular characteristics of individuals with SCA (including balance, gait, mobility, severity of ataxia, DNA test characteristics and non-ataxic signs) can be identified to predict their improvement in balance and gait following tDCS sessions; (ii) to investigate if an extended number of tDCS sessions, beyond the typical 5 to 10 sessions described in scientific literature, applied concomitantly with exercises with progressive challenges, to yield positive outcomes over some parameters of gait and postural control in individuals with SCA; (iii) To investigate, through semi-structured interviews, the subjective experience of the participants regarding the use of trans-spinal tDCS, about changes in health and quality of life, as well as the expectations that were achieved or frustrated with the intervention used; (iv) To investigate if there is retention of benefits a month after the end of the intervention; (v) propose a specific test to detect postural control deficits during head and limb movement; and (vi) analyze whether the specific characteristics evaluated in individuals correlate with each other.

Methods: This is a pragmatic clinical trial that will be carried out using the CONSORT-Pragmatic Trials. The present study will be carried out at the Deolindo Couto Institute of Neurology, at the Federal University of Rio de Janeiro - UFRJ (Avenida Venceslau Brás, 95 - Botafogo, Rio de Janeiro - RJ). Individuals with spinocerebellar ataxia of any type, who are part of the records of public hospitals, doctors' offices, and physiotherapists, will be invited to participate in the study.

Initially, individuals will be interviewed to research the eligibility criteria, by filling out an anamnesis form, which will also contain questions about their demographic data. Those who are eligible and agree to participate must express their consent by signing an informed consent form.

Up to 45 patients with SCA of different types will undergo a non-invasive stimulation plus gait and postural control training. The total duration of sessions will last 30 minutes during which participants will simultaneously receive 20 min of trans-spinal tDCS and perform a gait training protocol with progressively greater difficulties, previously tested in patients with SCA. The trans-spinal tDCS will be applied at an intensity of 2mA, with the anodic electrode positioned over the cerebellar region and the cathodic electrode over the thoracic region of the spinal cord (approximately vertebra T11). The intervention will be applied over four consecutive weeks on weekdays except weekends, totaling 20 sessions.

All participants will receive real stimulation, so there will be no control group. Given that it may be difficult to recruit additional SCA individuals willing to participate in a control group or to find patients with similar characteristics who do not receive treatment during the study period, also due to the progressively debilitating condition of the participants (SCA) and given their socio-economic conditions that limit their transportation, it would be ethically questionable to deprive a group of patients of receiving a potentially beneficial treatment, especially when there is no established standard therapy or other effective treatment options available to them.

The equipment to be used for stimulation will be an NKL Stimulator. The continuous current offered will be supplied through a pair of 5x7 cm (35 cm2) electrodes wrapped in sponges moistened with saline solution. The anode electrode will be positioned over the cerebellar region. To do this, the inion region will be located. Using a measuring tape, the point 2cm above the inion will be identified and the electrode will be fixed to the scalp, using appropriate adjustable bands. The cathode electrode will be positioned over the spinal region, more precisely, at the level of T8. To precisely find this position, the thoracic spinous processes will be palpated, and the 11th process located. Using a measuring tape, identify the point located 2 cm below T11 and fix the electrode with adhesive tape at this point. The stimulation intensity will be 2mA.

Initially, participants will be evaluated (ASSESSMENT 1) through the application of the SARA scale; modified dynamic gait index (mDGI); The Berg Balance Scale; Timed up and go (TUG); Inventory of non-ataxic signs (INAS); The four-stage test; Ten-meter walk test with an accelerometer; and perform other three tasks using an accelerometer of a mobile phone: (i) 5 times sit-to-stand; (ii) Functional Reach Test; and (iii) a test consisted in move arms and head standing with foot together. Three physiotherapist experts in these evaluations who will not participate in the intervention sessions will conduct this part. Then, 20 successive tDCS sessions will be applied to the participants. Every 5 tDCS sessions, the mDGI and TUG assessment will be reassessed (ASSESSMENT 2, 3, and 4). At the end of the 20 sessions, all instruments will be reapplied except for INAS (ASSESSMENT 5). A month after the end of the intervention the individuals will be reassessed except for the tests using the accelerometer (ASSESSMENT 6).

Before and after each session, individuals will be evaluated using the one-leg stand test proposed in the miniBestest instrument. In this test, the individual must remain standing, with their eyes open and fixed on a point 1.6 to 3m away with their hands on their waist. The participant must remove a lower limb from the support, without assistance, flexing it backward and remaining there. The time spent in the position will be measured in seconds, from the moment the evaluator says "now" until the elevated foot touches the ground again, or the upper limbs move from the initial position. The test will be repeated twice for each lower limb. Both times will be noted, and the highest time will be considered.

At the end of 20 sessions, individuals who complete the intervention will be also interviewed with a semi-structurally questionary by a researcher who did not take part in the study. The method that will be used to analyze the interviews will be the framework approach, which consists of a deductive form of analysis that starts from pre-defined research objectives. The framework approach is a systematic method that allows for in-depth analysis, in which the researcher extracts codes from the interviewees' statements, forms categories, and finally acquires refined themes useful for describing the participants' ideas and perceptions. All interviews will be conducted face-to-face. The interviews will be recorded for future transcription, using a smartphone. Once the interviews have been transcribed, the content will be analyzed using ATLAS.ti® software, and, finally, the themes that most faithfully represent the concepts found in the interviews will be chosen.

Eligibility criteria: Inclusion Criteria:

1. Individuals aged 18 to 70, without distinction of gender or ethnicity;
2. Diagnosed with spinocerebellar ataxia, of any type, by a neurologist;
3. With mild to moderate ataxia severity;
4. Able to walk 2 meters even when using a walker, cane or crutch;
5. Score ≥21 (BERTOLUCCI et al., 1994) on the Mini-Mental State Examination (MMSE; FOLSTEINet al., 1975; ALMEIDA, 1998);
6. No other concomitant neurological changes.

Exclusion Criteria:

1. Illiterate;
2. Being subjected to any other experimental physiotherapeutic or medicinal intervention during the clinical trial;
3. Skin condition that may affect the electrode placement site
4. Musculoskeletal, neurological or cardiorespiratory disorders that prevent the tests from being carried out;
5. Epilepsy;
6. Pregnancy;
7. History of brain surgery;
8. History of seizures;
9. Metallic implants in the skull that interfere with neuromodulation;

Primary outcomes:
measure: Postural control
timeFrame: (i) Baseline, (ii) after 20 sessions and (iii) in follow up (one month).
measure: Mobility
timeFrame: (ii) Baseline, (ii) at the end of sessions 5, 10, 15 and 20 (each session is 1 day) and (iii) in follow up (one month)
measure: Gait performance
timeFrame: (ii) Baseline, (ii) at the end of sessions 5, 10, 15 and 20 (each session is 1 day) and (iii) in follow up (one month)
measure: Accelerometry
timeFrame: (i) Baseline and (ii) after 20 sessions.
Secondary outcomes:
measure: The subjective experience of the participants regarding the protocol.
timeFrame: At the end of session 20 (each session is 1 day)
measure: The presence of non ataxic signals (INAS) and the disease severity (SARA)
timeFrame: (i) Baseline and (ii) after 20 sessions.
Other outcomes:
Locations:
city: Rio de Janeiro
country: Brazil
facility: Instituto de Neurologia Deolindo Couto
state: RJ
Study officials:
affiliation: Centro Universitário Augusto Motta
name: LAURA OLIVEIRA, PT PHD
role: STUDY_DIRECTOR
affiliation: Centro Universitário Augusto Motta
name: ANNA FONTES BAPTISTA, PT
role: PRINCIPAL_INVESTIGATOR
affiliation: Centro Universitário Augusto Motta
name: Eduardo S Moreira, PT
role: STUDY_CHAIR
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