Ignite Creation Date:
2024-05-06 @ 6:38 PM
Last Modification Date:
2024-10-26 @ 2:51 PM
Study NCT ID:
NCT05720871
Status:
RECRUITING
Last Update Posted:
2023-02-13
First Post:
2023-01-17
Brief Title:
Treatment of Chronic Post-stroke Oropharyngeal Dysphagia With Paired Stimulation
Sponsor:
Hospital de Mataró
Organization:
Hospital de Mataró
Study Overview
Official Title:
Treatment of Chronic Post-stroke Oropharyngeal Dysphagia With Paired Stimulation Through Peripheral TRVP1 Agonists and Non-invasive Brain Stimulation
Status:
RECRUITING
Status Verified Date:
2023-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
ICI2000117
Brief Summary:
According WHO oropharyngeal dysphagia OD is a prevalent post-stroke PS condition involving the digestive system ICD-10 I69391 and an independent risk factor for malnutrition and pulmonary infection and leads to greater morbimortality and healthcare costs and poorer quality of life QoL Currently OD therapy is mainly compensatory with low rates of compliance and small benefit and there is no pharmacological treatment so new treatments that improve patients condition are crucial PS-OD patients present both oropharyngeal sensory and motor deficits so neurorehabilitation treatments which target both could be optimum Benefits of paired peripheral sensory stimulation with oral capsaicin and of central motor noninvasive brain stimulation techniques such as transcranial direct current stimulation tDCS and repetitive transcranial magnetic stimulation rTMS will be studied Pairing pharmacological peripheral and central stimulation may produce greater benefits The main aim of the project is to study the efficacy of two novel protocols of paired stimulation on PS-OD patients The investigators will assess whether 5-day application of tDCScapsaicin or rTMScapsaicin in the chronic phase of stroke will improve PS-OD One RCT 200 patients in the chronic stroke phase divided in 4 study arms will assess changes in swallow safety biomechanics and neurophysiology of the swallow response hospital stay respiratory and nutritional complications mortality and QoL
Detailed Description:
Main hypothesis Paired neurorehabilitation treatment targeting both pharyngeal sensory and motor components simultaneously through a peripheral pharmacological stimulant Transient Receptor Potential Cation Channel TRPV1 agonist capsaicin and central stimulation NIBS strategies rTMS or tDCS can improve swallowing function in chronic PS-OD patients by promoting cortical plasticity their QoL and reduce OD associated complications
Main aim To assess the effects on swallowing of 2 neurostimulation strategies applied for 5 days to treat PS-OD in the chronic phase 3 months from stroke onset of ambulatory patients the application of rTMS capsaicin vs tDCS capsaicin in two independent RCTs The main outcome measure for these three RCTs will be changes in prevalence of impaired safety of swallow assessed by videofluoroscopy
Secondary aims To assess 1 safety and adverse events 2 the effects on safety of swallow with a standardized protocol of swallowing evaluation 3 clinical outcomes at 3 months follow up 4 the effect of the treatments on SSF and responsiveness to treatment according to stroke characteristics 5 the effect in the chronic phase on i assessment of afferent and efferent pathways with sensory and motor evoked-potentials to electrical pharyngeal stimulation and TMS respectively ii prevalence of signs of impaired safetyefficacy on videofluoroscopy VFS the penetration-aspiration score PAS Rosenbek scale and the biomechanics of the swallow response and iii specific clinical outcomes such as mid-term complications readmission rate and QoL
Design Single-center double-blinded two-arm double-randomization RCT Patients are distributed into two parallel subgroups each with its own sham group according to intervention typeBlinding will be applicable for clinical and instrumental assessments for investigators and for intervention condition for patients Patients undergo V-VST biomechanical VFS and neurophysiological sEMG and evoked potentials swallowing evaluation and double randomization first for intervention type tDCS or rTMS and then for intervention condition active or sham using the same software as Task1 Treatment is applied for 5 consecutive days using either rTMS G1 active rTMScapsaicin G2 sham rTMSplacebo or tDCS G1 active tDCScapsaicin G2 sham tDCSplacebo as NIBS procedures Finally patients are reevaluated as before and clinical outcome at 3 months
Study population 200 Chronic PS-OD ambulatory patients
Inclusion criteria Chronic 3 and 24 months unilateral hemispheric stroke adult patients ISS V-VST can follow the study protocol and give written informed consent
Exclusion criteria Pregnancy life expectancy 3m or palliative care neurodegenerative disorder or previous OD implanted electronic device epilepsy metal in the head participation in another clinical trial in the previous month
Sample sizepower calculation The main outcome measure is the prevalence of patients with ISS according to VFS at post-treatment visit To compare the prevalence between groups using the arcsinus approximation accepting an alpha risk of 005 and a beta risk of 02 in a 2-sided test 50 patientsgroup are needed for each NIBS procedure 2 for rTMS and 2 for tDCS 4 groupstotal of 200 patients to find a significant difference in the proportion of 04 in the control group and 07 in treated group drop-out rate of 15
Recruitment Patients will be consecutively recruited and randomly allocated to the groups according first to NIBS procedure 11 tDCSrTMS and then to intervention condition 11 activesham
Study Intervention
tDCS G1 Active treatment consists of swallowing 10mL capsaicin 150μM and just after of applying 30min of 20mA tDCS DC-Stimulator Plus NeuroConn Germany with the anode placed over the pharyngeal primary motor cortex M1 of the unaffected hemisphere 35cm lateral 1cm anterior to the vertex and the cathode over the opposite supraorbital region Treatment applied over 5 consecutive days
rTMS G1 each session 5 consecutive days of active treatment consists of swallowing 10mL capsaicin 150μM and just after of applying focal alpha D70 coil rTMS Magstim Rapid2 UK over the pharyngeal M1 hotspot of the unaffected hemisphere Neuronavigation Brainsight TMS navigation UK ensures the exact hotspot over 5 days A total of 500 pulsessession are delivered consisting of 10 5Hz-trains of 10s of 50 pulses each total 2500 pulses with a 1min interval between trains at an intensity of 90 of the resting motor threshold RMT G2 Sham rTMSoral placebo 10mL of potassium sorbate The same protocol will be applied but with the coil tilted 90º from the tangent of the skull as a standard method for sham rTMS application
Swallowing assessment pre- and post-intervention Patients with impaired safety of swallow will be screened with volume-viscosity swallowing test V-VST and videofluoroscopy VFS recordings are obtained in a lateral projection 25 framess Swallow biomechanics are analyzed at VFS with Swallowing Observer ImagePhysiology SL Spain The spontaneous swallowing frequency SSF during 10min will be measured with surface electromyography sEMG over the digastric-mylohyoid complex
Pharyngeal sensory evoked potentials pSEPs are recorded with a 32-electrode electroencephalographic EEG recording cap 1020 system during a series of electrical stimuli 4 sets of 50 pulses of 02ms at 02Hz intensity of 75 tolerance threshold Digitimer DS7A DG2A pulse generator UK applied to the pharynx with an intra-pharyngeal catheter Gaeltec Ltd Scotland
Pharyngeal motor evoked potentials pMEPs and RMTs for both hemispheres are recorded with the same catheter to TMS 20 pulses to each hotspot at intensity 20RMT Magstim Bistim2 UK
Primary outcomes Pre- vs post-intervention changes in VFS signs of safety and efficacy of swallow PAS scoring timing of swallow response and amplitude and latency of pSEPs and pMEPs
Secondary outcomes Prepost-intervention changes in sEMG for SSF safety adverse events rate clinical outcomes during admission and at 3-month follow-up length of stay aspiration pneumonia nutritional MNA-sf and functional status Rankin scale Barthel readmissions and mortality and V-VST at 3 months
Additional secondary outcomes differences in the magnitude of the effect in primary outcomes found in chronic PS phase between the tDCS capsaicin and rTMS capsaicin interventions
Main aim To assess the effects on swallowing of 2 neurostimulation strategies applied for 5 days to treat PS-OD in the chronic phase 3 months from stroke onset of ambulatory patients the application of rTMS capsaicin vs tDCS capsaicin in two independent RCTs The main outcome measure for these three RCTs will be changes in prevalence of impaired safety of swallow assessed by videofluoroscopy
Secondary aims To assess 1 safety and adverse events 2 the effects on safety of swallow with a standardized protocol of swallowing evaluation 3 clinical outcomes at 3 months follow up 4 the effect of the treatments on SSF and responsiveness to treatment according to stroke characteristics 5 the effect in the chronic phase on i assessment of afferent and efferent pathways with sensory and motor evoked-potentials to electrical pharyngeal stimulation and TMS respectively ii prevalence of signs of impaired safetyefficacy on videofluoroscopy VFS the penetration-aspiration score PAS Rosenbek scale and the biomechanics of the swallow response and iii specific clinical outcomes such as mid-term complications readmission rate and QoL
Design Single-center double-blinded two-arm double-randomization RCT Patients are distributed into two parallel subgroups each with its own sham group according to intervention typeBlinding will be applicable for clinical and instrumental assessments for investigators and for intervention condition for patients Patients undergo V-VST biomechanical VFS and neurophysiological sEMG and evoked potentials swallowing evaluation and double randomization first for intervention type tDCS or rTMS and then for intervention condition active or sham using the same software as Task1 Treatment is applied for 5 consecutive days using either rTMS G1 active rTMScapsaicin G2 sham rTMSplacebo or tDCS G1 active tDCScapsaicin G2 sham tDCSplacebo as NIBS procedures Finally patients are reevaluated as before and clinical outcome at 3 months
Study population 200 Chronic PS-OD ambulatory patients
Inclusion criteria Chronic 3 and 24 months unilateral hemispheric stroke adult patients ISS V-VST can follow the study protocol and give written informed consent
Exclusion criteria Pregnancy life expectancy 3m or palliative care neurodegenerative disorder or previous OD implanted electronic device epilepsy metal in the head participation in another clinical trial in the previous month
Sample sizepower calculation The main outcome measure is the prevalence of patients with ISS according to VFS at post-treatment visit To compare the prevalence between groups using the arcsinus approximation accepting an alpha risk of 005 and a beta risk of 02 in a 2-sided test 50 patientsgroup are needed for each NIBS procedure 2 for rTMS and 2 for tDCS 4 groupstotal of 200 patients to find a significant difference in the proportion of 04 in the control group and 07 in treated group drop-out rate of 15
Recruitment Patients will be consecutively recruited and randomly allocated to the groups according first to NIBS procedure 11 tDCSrTMS and then to intervention condition 11 activesham
Study Intervention
tDCS G1 Active treatment consists of swallowing 10mL capsaicin 150μM and just after of applying 30min of 20mA tDCS DC-Stimulator Plus NeuroConn Germany with the anode placed over the pharyngeal primary motor cortex M1 of the unaffected hemisphere 35cm lateral 1cm anterior to the vertex and the cathode over the opposite supraorbital region Treatment applied over 5 consecutive days
rTMS G1 each session 5 consecutive days of active treatment consists of swallowing 10mL capsaicin 150μM and just after of applying focal alpha D70 coil rTMS Magstim Rapid2 UK over the pharyngeal M1 hotspot of the unaffected hemisphere Neuronavigation Brainsight TMS navigation UK ensures the exact hotspot over 5 days A total of 500 pulsessession are delivered consisting of 10 5Hz-trains of 10s of 50 pulses each total 2500 pulses with a 1min interval between trains at an intensity of 90 of the resting motor threshold RMT G2 Sham rTMSoral placebo 10mL of potassium sorbate The same protocol will be applied but with the coil tilted 90º from the tangent of the skull as a standard method for sham rTMS application
Swallowing assessment pre- and post-intervention Patients with impaired safety of swallow will be screened with volume-viscosity swallowing test V-VST and videofluoroscopy VFS recordings are obtained in a lateral projection 25 framess Swallow biomechanics are analyzed at VFS with Swallowing Observer ImagePhysiology SL Spain The spontaneous swallowing frequency SSF during 10min will be measured with surface electromyography sEMG over the digastric-mylohyoid complex
Pharyngeal sensory evoked potentials pSEPs are recorded with a 32-electrode electroencephalographic EEG recording cap 1020 system during a series of electrical stimuli 4 sets of 50 pulses of 02ms at 02Hz intensity of 75 tolerance threshold Digitimer DS7A DG2A pulse generator UK applied to the pharynx with an intra-pharyngeal catheter Gaeltec Ltd Scotland
Pharyngeal motor evoked potentials pMEPs and RMTs for both hemispheres are recorded with the same catheter to TMS 20 pulses to each hotspot at intensity 20RMT Magstim Bistim2 UK
Primary outcomes Pre- vs post-intervention changes in VFS signs of safety and efficacy of swallow PAS scoring timing of swallow response and amplitude and latency of pSEPs and pMEPs
Secondary outcomes Prepost-intervention changes in sEMG for SSF safety adverse events rate clinical outcomes during admission and at 3-month follow-up length of stay aspiration pneumonia nutritional MNA-sf and functional status Rankin scale Barthel readmissions and mortality and V-VST at 3 months
Additional secondary outcomes differences in the magnitude of the effect in primary outcomes found in chronic PS phase between the tDCS capsaicin and rTMS capsaicin interventions
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None