Ignite Creation Date:
2024-05-06 @ 8:25 PM
Last Modification Date:
2024-10-26 @ 3:27 PM
Study NCT ID:
NCT06374693
Status:
RECRUITING
Last Update Posted:
2024-04-19
First Post:
2024-03-25
Brief Title:
Investigating the Tolerability and Feasibility of tVNS Following aSAH
Sponsor:
Sheffield Teaching Hospitals NHS Foundation Trust
Organization:
Sheffield Teaching Hospitals NHS Foundation Trust
Study Overview
Official Title:
Investigating the Tolerability and Feasibility of Transcutaneous Vagus Nerve Stimulation Following Aneurysmal Subarachnoid Haemorrhage
Status:
RECRUITING
Status Verified Date:
2024-08
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:
tVNS in aSAH
Brief Summary:
After a subarachnoid haemorrhage complications are common and increase the overall rate of disability and death from the condition Despite some advances in preventing detecting and treating these complications the rates of complications and associated risks remain high Further research into ways to reduce complications of subarachnoid haemorrhage
Transcutaneous vagus nerve stimulation tVNS is a technique where a small handheld device is attached to an earpiece which stimulates the nerves to the ear This is given for short periods and may help improve blood flow and reduce inflammation in the brain The intervention has been safely used and licensed in seizures headache and severe depression
This study will look to see if it is feasible and tolerable to have tVNS twice daily for 5 days after subarachnoid haemorrhage and whether it can help reduce the risk of complications from subarachnoid haemorrhage
The participant will be randomly allocated to receive either tVNS or a dummy intervention known as sham
The researchers will collect some personal and clinical details such as diagnosis medications age blood test results as well as some details about the subarachnoid haemorrhage
The researchers will also complete brief questionnaires with the participant to assess symptoms They will take measurements of heart rate pupil response and brain activity using a cap The participant will then be randomly allocated to either receive the tVNS or sham intervention
Next the research team will apply the earpiece to their ear twice a day for 45 minutes for a total of 5 days
At the end of the 5-day study period the intervention will be complete The researchers will arrange a follow-up meeting on discharge and at 6 weeks to assess the participants symptoms and recovery
Previous studies have shown that tVNS is safe and well tolerated including a recent review of tVNS studies which evaluated the side effects experienced by 1322 patients receiving tVNS
The main side effects include localised tinglingnumbnesspainredness around the ear 17 headaches 3 dizziness 1 facial droop 1 nausea 1 nasal discharge 2 Rarely palpitations or a slow heart rate may occur
They will continue to receive full medical treatment and observation alongside the study They are free to withdraw from this study if they find it too demanding on top of their other activities
Transcutaneous vagus nerve stimulation tVNS is a technique where a small handheld device is attached to an earpiece which stimulates the nerves to the ear This is given for short periods and may help improve blood flow and reduce inflammation in the brain The intervention has been safely used and licensed in seizures headache and severe depression
This study will look to see if it is feasible and tolerable to have tVNS twice daily for 5 days after subarachnoid haemorrhage and whether it can help reduce the risk of complications from subarachnoid haemorrhage
The participant will be randomly allocated to receive either tVNS or a dummy intervention known as sham
The researchers will collect some personal and clinical details such as diagnosis medications age blood test results as well as some details about the subarachnoid haemorrhage
The researchers will also complete brief questionnaires with the participant to assess symptoms They will take measurements of heart rate pupil response and brain activity using a cap The participant will then be randomly allocated to either receive the tVNS or sham intervention
Next the research team will apply the earpiece to their ear twice a day for 45 minutes for a total of 5 days
At the end of the 5-day study period the intervention will be complete The researchers will arrange a follow-up meeting on discharge and at 6 weeks to assess the participants symptoms and recovery
Previous studies have shown that tVNS is safe and well tolerated including a recent review of tVNS studies which evaluated the side effects experienced by 1322 patients receiving tVNS
The main side effects include localised tinglingnumbnesspainredness around the ear 17 headaches 3 dizziness 1 facial droop 1 nausea 1 nasal discharge 2 Rarely palpitations or a slow heart rate may occur
They will continue to receive full medical treatment and observation alongside the study They are free to withdraw from this study if they find it too demanding on top of their other activities
Detailed Description:
The aims of the study will be to conduct a pilot RCT to investigate whether tVNS is a tolerable and feasible treatment for acute aSAH To understand this the investigators will recruit participants who have recently undergone acute securing procedures follow acute aSAH coiling or clipping of aneurysm to a 5 day programme of intervention active tVNS vs sham and collect outcome data primary and secondary as per outcomes section The investigators will evaluate whether pre-defined success criteria are achieved for tolerability and feasibility and explore signals of effect on clinical outcome measures and mechanistic measures Non-invasive vagal nerve stimulation has not been studied in the acute period following aSAH outside of the remit of reducing headache This should offer critical insights as to whether this intervention has potential to take forward to a larger phase 23 clinical study
This is a single centre pilot randomised controlled trial 30 participants who have suffered an aneurysmal subarachnoid haemorrhage and had their aneurysm secured coiled or clipped successfully
The intervention will take place for 45 minutes twice a day for 5 days after securing the aneurysm The placebo group will receive the same intervention but the device will be in sham mode ie attached to the earlobe
It is not known whether tVNS is tolerable and feasible in aSAH but standard device settings will be used in accordance with a majority of other studies Similarly the optimal therapeutic duration is not known - 45 minutes twice a day is a similar usage to other studies A 5-day course has been chosen because it covers the highest risk period for DCI and is feasible for the research team to deliver
This is a single centre pilot single blind randomised placebo - controlled study
This has been chosen as it will demonstrate feasibility and tolerability whilst providing early data to indicate whether tVNS may provide benefit in this setting supporting the development of a larger RCT to establish whether it is a statistically significant benefit
Patients may be able to tell the different between an activated device and sham where the device is applied to the earlobe instead of the tragus However they will not experience both settings and the investigators will make no clear distinction of exactly what they should feel
A sample size of at least 30 has been chosen based on the number or participants required for the purposes of a feasibility assessment9 It is also a practically feasible number of participants to recruit based on annual admission numbers of patients to the RHH Royal Hallamshire Hospital Sheffield and the timeframe of the recruitment period
Potential participants with aSAH will be identified on admission to neurosurgery at RHH and approached about the study by the clinical treating team on the basis of convenience sampling If they are interested in the study they will be provided with an information sheet again and the opportunity to discuss the study with a member of the research team If they are willing to take part in the study written informed consent will be obtained after a screening consent support tool is used to ensure the patient had adequate comprehension
Capacity to consent to the study would be determined by the treating clinical team and confirmed by the research team according to the principles of the mental capacity act MCA 2005 Where the patient lacks capacity to consent including sedatedintubate patients a personal or nominated consultee can provide advice on what they feel the patients wishes would be if they had capacity The treating clinical team would introduce the study to the consultee and an information leaflet given to them The consultee would then have the option to sign a consent form if they believed the patient would agree to participate In accordance with the MCA 2005 ongoing consent or assent would be sought from the individual or consultee at each study visit before any research activity at the that visit is undertaken Consultees may advise at any point that they believe the persons wishes about participation have changed and they should therefore be withdrawn from the study Agitated patients will not receive the intervention if they are unable to tolerate it
The investigators are using tVNS settings that are widely used in other neurological conditions epilepsy migraine14 These include
Pulse width - 25ms
Frequency - device default 20 or 25Hz
Intensity - below pain threshold
Frequency - 45 minutes twice daily On the basis of similarity to other studies practicalities on the ward and clinical scenario
The investigators have chosen a duration of 5 days based on the usual clinical pathway of inpatient management at the Royal Hallamshire Hospital and have chosen to deliver the treatment twice daily to optimise the dose This is a pilot study with feasibility outcomes and as such the investigators will be exploring the feasibility of this treatment regimen
The Parasym Device will be applied to the left tragus figure 1 as this is the most common site for tVNS delivery in neurological studies and is associated with few afferents to the heart
The intervention is aimed at supplementing routine clinical care and as such the doses of tVNS can be interrupted for care activities therapy sessions examinations assessments etc and resume afterwards The overall minute duration will aim to remain 45 minutes twice daily
The active intervention will be compared to sham tVNS where the vagal nerve stimulator will be attached to the earlobe instead of the tragus in keeping with evidence that this does not cause vagus nerve stimulation and is in line with sham methods used in other studies The investigators do not anticipate that patients will have the intervention long enough to become familiar with the common sensations associated with true tVNS intervention At the end of the intervention period participants will be asked if they thought they had received true of sham tVNS to understand the blinding ability of the sham
The investigators will use the FNIRS Lumo ecosystem Gower labs to assess cerebral blood flow in the frontal lobes The investigators will complete a protocol where 6 optodes are placed bilaterally over the frontal and prefrontal cortices The investigators will complete and record resting state signals of oxyhaemoglobin and deoxyhaemoglobin for 5 minutes while patients are laid in bed with their eyes closed or wearing an eye patch Following the 5-minute rest phase vagal nerve stimulation or sham stimulation will start depending on the participants randomisation and signal acquisition will continue for 5 minutes After this time the stimulation will cease and a further 5 minutes of resting signal acquisition will be completed The data acquired during this protocol will undergo processing adjustment for background and physiological noise and data analysis using recommended software Homer 23 Data analysis will look to compare signal acquisition between resting and stimulation states and will evaluate any lasting effects of stimulation following termination The investigators will perform this on the first and last day of the intervention before and after stimulation respectively
The investigators will be using Reflex Pupillometry to measure pupillograms in response to a light stimulus during an intervention session for all participants This will be done at a different time to the Lumo FNIRS assessment Recording of the pupillary response will follow the following protocol 3 baseline measures taken 1 minute apart prior to stimulation will represent baseline pupillograms which will be averaged Following this stimulation active or sham will start and 3 times pupillograms will be measured at 1 minute intervals following initiation After completion of the treatment session 3 further pupillograms separated by 1-minute intervals will be measured - that will constitute the recovery phase
Enrolled participants will be issued with a study number and randomised 21 SealedEnvelope Ltd stratified according to age lt65 and 65 years They will then receive either active tVNS stimulation tragus or sham earlobe twice daily for 45 minutes per session for 5 days The investigators do not anticipate discharges from hospital earlier than 5 days as this is not routine practice in the neurosurgical unit
Primary outcome measures of tolerability and feasibility will be collected daily by researchers delivering the intervention and secondary outcome measures will be collected at the end of intervention or on hospital discharge as detailed in figure 2
Following discharge from hospital participants will return for follow up clinic assessment at 4 weeks where questionnaire measures of functional recovery and adverse event reporting will be undertaken After this the participants involvement in the study will be complete
The analyses will be undertaken on statistical software PRISM and will compare the two groups Rates of complications and outcomes will be reported descriptively Data integrity will be checked by two researchers and inputted contemporaneously Each researcher will be trained in outcome measures prior to study initiation
This is a single centre pilot randomised controlled trial 30 participants who have suffered an aneurysmal subarachnoid haemorrhage and had their aneurysm secured coiled or clipped successfully
The intervention will take place for 45 minutes twice a day for 5 days after securing the aneurysm The placebo group will receive the same intervention but the device will be in sham mode ie attached to the earlobe
It is not known whether tVNS is tolerable and feasible in aSAH but standard device settings will be used in accordance with a majority of other studies Similarly the optimal therapeutic duration is not known - 45 minutes twice a day is a similar usage to other studies A 5-day course has been chosen because it covers the highest risk period for DCI and is feasible for the research team to deliver
This is a single centre pilot single blind randomised placebo - controlled study
This has been chosen as it will demonstrate feasibility and tolerability whilst providing early data to indicate whether tVNS may provide benefit in this setting supporting the development of a larger RCT to establish whether it is a statistically significant benefit
Patients may be able to tell the different between an activated device and sham where the device is applied to the earlobe instead of the tragus However they will not experience both settings and the investigators will make no clear distinction of exactly what they should feel
A sample size of at least 30 has been chosen based on the number or participants required for the purposes of a feasibility assessment9 It is also a practically feasible number of participants to recruit based on annual admission numbers of patients to the RHH Royal Hallamshire Hospital Sheffield and the timeframe of the recruitment period
Potential participants with aSAH will be identified on admission to neurosurgery at RHH and approached about the study by the clinical treating team on the basis of convenience sampling If they are interested in the study they will be provided with an information sheet again and the opportunity to discuss the study with a member of the research team If they are willing to take part in the study written informed consent will be obtained after a screening consent support tool is used to ensure the patient had adequate comprehension
Capacity to consent to the study would be determined by the treating clinical team and confirmed by the research team according to the principles of the mental capacity act MCA 2005 Where the patient lacks capacity to consent including sedatedintubate patients a personal or nominated consultee can provide advice on what they feel the patients wishes would be if they had capacity The treating clinical team would introduce the study to the consultee and an information leaflet given to them The consultee would then have the option to sign a consent form if they believed the patient would agree to participate In accordance with the MCA 2005 ongoing consent or assent would be sought from the individual or consultee at each study visit before any research activity at the that visit is undertaken Consultees may advise at any point that they believe the persons wishes about participation have changed and they should therefore be withdrawn from the study Agitated patients will not receive the intervention if they are unable to tolerate it
The investigators are using tVNS settings that are widely used in other neurological conditions epilepsy migraine14 These include
Pulse width - 25ms
Frequency - device default 20 or 25Hz
Intensity - below pain threshold
Frequency - 45 minutes twice daily On the basis of similarity to other studies practicalities on the ward and clinical scenario
The investigators have chosen a duration of 5 days based on the usual clinical pathway of inpatient management at the Royal Hallamshire Hospital and have chosen to deliver the treatment twice daily to optimise the dose This is a pilot study with feasibility outcomes and as such the investigators will be exploring the feasibility of this treatment regimen
The Parasym Device will be applied to the left tragus figure 1 as this is the most common site for tVNS delivery in neurological studies and is associated with few afferents to the heart
The intervention is aimed at supplementing routine clinical care and as such the doses of tVNS can be interrupted for care activities therapy sessions examinations assessments etc and resume afterwards The overall minute duration will aim to remain 45 minutes twice daily
The active intervention will be compared to sham tVNS where the vagal nerve stimulator will be attached to the earlobe instead of the tragus in keeping with evidence that this does not cause vagus nerve stimulation and is in line with sham methods used in other studies The investigators do not anticipate that patients will have the intervention long enough to become familiar with the common sensations associated with true tVNS intervention At the end of the intervention period participants will be asked if they thought they had received true of sham tVNS to understand the blinding ability of the sham
The investigators will use the FNIRS Lumo ecosystem Gower labs to assess cerebral blood flow in the frontal lobes The investigators will complete a protocol where 6 optodes are placed bilaterally over the frontal and prefrontal cortices The investigators will complete and record resting state signals of oxyhaemoglobin and deoxyhaemoglobin for 5 minutes while patients are laid in bed with their eyes closed or wearing an eye patch Following the 5-minute rest phase vagal nerve stimulation or sham stimulation will start depending on the participants randomisation and signal acquisition will continue for 5 minutes After this time the stimulation will cease and a further 5 minutes of resting signal acquisition will be completed The data acquired during this protocol will undergo processing adjustment for background and physiological noise and data analysis using recommended software Homer 23 Data analysis will look to compare signal acquisition between resting and stimulation states and will evaluate any lasting effects of stimulation following termination The investigators will perform this on the first and last day of the intervention before and after stimulation respectively
The investigators will be using Reflex Pupillometry to measure pupillograms in response to a light stimulus during an intervention session for all participants This will be done at a different time to the Lumo FNIRS assessment Recording of the pupillary response will follow the following protocol 3 baseline measures taken 1 minute apart prior to stimulation will represent baseline pupillograms which will be averaged Following this stimulation active or sham will start and 3 times pupillograms will be measured at 1 minute intervals following initiation After completion of the treatment session 3 further pupillograms separated by 1-minute intervals will be measured - that will constitute the recovery phase
Enrolled participants will be issued with a study number and randomised 21 SealedEnvelope Ltd stratified according to age lt65 and 65 years They will then receive either active tVNS stimulation tragus or sham earlobe twice daily for 45 minutes per session for 5 days The investigators do not anticipate discharges from hospital earlier than 5 days as this is not routine practice in the neurosurgical unit
Primary outcome measures of tolerability and feasibility will be collected daily by researchers delivering the intervention and secondary outcome measures will be collected at the end of intervention or on hospital discharge as detailed in figure 2
Following discharge from hospital participants will return for follow up clinic assessment at 4 weeks where questionnaire measures of functional recovery and adverse event reporting will be undertaken After this the participants involvement in the study will be complete
The analyses will be undertaken on statistical software PRISM and will compare the two groups Rates of complications and outcomes will be reported descriptively Data integrity will be checked by two researchers and inputted contemporaneously Each researcher will be trained in outcome measures prior to study initiation
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?:
False
Is an FDA AA801 Violation?:
None