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Trial registered on ANZCTR


Registration number
ACTRN12624000216516
Ethics application status
Approved
Date submitted
11/02/2024
Date registered
5/03/2024
Date last updated
5/03/2024
Date data sharing statement initially provided
5/03/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Vestibular neuromodulation for the treatment of persistent pain: An open label case series
Scientific title
Vestibular neuromodulation for the treatment of persistent pain: An open label case series
Secondary ID [1] 311212 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent pain 332409 0
Neck pain 332411 0
Back pain 332412 0
Limb pain 332413 0
Neuropathic pain 332414 0
Complex regional pain syndrome 332415 0
Persistent post-surgery spinal pain syndrome 332416 0
Nociplastic pain with central sensitisation 332417 0
Post stroke central pain 332418 0
Phantom limb pain 332419 0
Condition category
Condition code
Anaesthesiology 329110 329110 0 0
Pain management
Neurological 329797 329797 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Caloric vestibular stimulation (detailed below) is administered by Dr Steven Miller (medical practitioner) at Monash University, Clayton, or Dr Murray Taverner (pain specialist) or trained pain specialists/pain fellows at Frankston Pain Management Clinic, on a non-randomised, convenience (patient-availability) basis, with one right ear CVS administration per attendance. CVS is administered for up to six sessions, with CVS never repeated on the same day. The usual frequency of administration is once per week, however can be increased to daily administration (3x/week over two weeks) and may occasionally be reduced to as infrequent as once per month for 6 months if required by patient availability or if each CVS session provides as much as 1 month’s relief. To reiterate though, the standard administration frequency is once per week for 6 weeks. The two instances in which more than 6 sessions of CVS is administered include: (i) if there is a change from right ear to left CVS if right ear CVS is not appearing to be of any benefit, and (ii) an option for patients to repeat the 6 sessions of right ear CVS for patients in whom the first six sessions delivered pain/function benefits and in whom the beneficial effects have worn off by the review date 6 weeks after the last CVS session.

There is no control condition as this is an open-label case series. To prevent potential confounding from different interventions or medication changes, there is an expressed preference for patients to not undergo any other new pain intervention treatment or medication change during the course of their involvement in the study, but this is not mandated.

CVS is administered with patients seated or lying with their head angled upward 30° from horizontal. Up to 50mls of cold water (16°C) is slowly irrigated into the right external ear canal using a syringe with attached plastic cannula tubing (with the needle removed) which is situated close to, but not touching, the tympanic membrane. To ensure maximal stimulation, irrigation is continued for 5–10 seconds after nystagmus onset. Nystagmus and vertigo are elicited in all patients and persists for 2–5 minutes. Occasionally if 50mls of cold water has failed to elicit vestibular stimulation, a second 50mls can be administered. Most often less than 50mls is required. Also occasionally, and only with the patient’s consent, a failure to elicit CVS with 16°C water can result in a further attempt to elicit the stimulation with iced water (0-4°C). The latter was the water temperature used in our previous research, however data exist that the CVS and nystagmus elicited is equivalent when using 16°C or 0-4°C water (and 16°C water is more comfortable to receive than 0-4°C water).

One reason for failure to elicit CVS with either 16°C or 0-4°C water irrigation is ear wax blockage of the ear canal. If this is present and preventing CVS from occurring, there is the option to apply ear wax removal drops for several days prior to the second attendance. If CVS still does not occur, the patient may need to see their general practitioner for ear wax removal prior to attending for CVS again.

Patients are advised that it is preferable that someone attend with them to drive them home after the CVS session, however if they are free from significant side effects, they are able to drive themselves home if required.

The follow up sessions at 6 weeks after the last CVS session and at 6 months after the last CVS session are preferred to be conducted in person, however can be conducted via telephone or video calling if required. The administering medical practitioner will be responsible for determining that you are safe to leave.

The first attendance will take around 2 hours given the history required to be elicited and the detailed questionnaire assessments. Subsequent CVS sessions will last closer to 1 hour given less time required for history taking and less outcome measure collection. The 3rd and 6th CVS sessions are closer to 1.25-1.5 hours due to longer assessments. Attendance will be during business hours Mon-Fri at a time of investigator and patient convenience.
Intervention code [1] 327675 0
Treatment: Other
Comparator / control treatment
No comparator or control treatment
Control group
Uncontrolled

Outcomes
Primary outcome [1] 336928 0
Persistent pain
Timepoint [1] 336928 0
Brief Pain Inventory - Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (primary timepoint), 6 months after last CVS session
Primary outcome [2] 337361 0
Functional capacity
Timepoint [2] 337361 0
Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (primary timepoint), 6 months after last CVS session
Primary outcome [3] 337362 0
Allodynia (in cases who have this clinical feature)
Timepoint [3] 337362 0
Baseline, before and after CVS (10mins and 20mins), daily via pain diary, 6 weeks after last CVS session (primary timepoint), 6 months after last CVS session.
For the daily assessment in the pain diary between CVS sessions, the patient self-tests in a similar way rather than the examiner.
Secondary outcome [1] 430181 0
Neuropathic pain
Timepoint [1] 430181 0
Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (secondary timepoint), 6 months after last CVS session
Secondary outcome [2] 430182 0
Depression/anxiety/stress (a conglomerate measure)
Timepoint [2] 430182 0
Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (secondary timepoint), 6 months after last CVS session
Secondary outcome [3] 430183 0
Confidence of a person with persistent pain to do a range of activities while in pain
Timepoint [3] 430183 0
Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (secondary timepoint), 6 months after last CVS session
Secondary outcome [4] 430184 0
Functional tolerances
Timepoint [4] 430184 0
Baseline, after 3rd and 6th CVS session, 6 weeks after last CVS session (secondary timepoint), 6 months after last CVS session
Secondary outcome [5] 430185 0
Mood
Timepoint [5] 430185 0
Baseline, at each CVS attendance, 6 weeks after last CVS session (secondary timepoint), 6 months after last CVS session.
Secondary outcome [6] 430186 0
CVS tolerability
Timepoint [6] 430186 0
At each CVS attendance, 6 weeks after last CVS session, 6 months after last CVS session
Secondary outcome [7] 432362 0
Subjective numerical pain rating scale (NRS) score (1-10); this is an additional primary outcome
Timepoint [7] 432362 0
Subjective NRS score – baseline, before and after CVS (10mins and 20mins), daily
via pain diary, 6 weeks after last CVS session (primary timepoint), 6 months after last CVS session

Eligibility
Key inclusion criteria
Patients with persistent pain (PP). This includes any pain condition that can present to a pain specialist, with the exception of spinal cord injury pain, visceral/abdominal/pelvic pain, and purely nociceptive musculoskeletal pain. A non- exhaustive list of the types of PP patients to be recruited includes those with: persistent neck pain, back pain, upper or lower limb pain, neuropathic pain (such as due to diabetes, chemotherapy, post-herpetic neuralgia, occipital neuralgia, trigeminal neuralgia), complex regional pain syndrome, failed back surgery syndrome (persistent post-spinal surgery pain syndrome), nociplastic pain with central sensitisation, post-stroke central pain syndrome (thalamic pain syndrome), and phantom limb pain.
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
(i) Younger than 18 or older than 70 (simple precaution exclusion)
(ii) Spinal cord injury pain, visceral/abdominal/pelvic pain, purely nociceptive pain (spinal cord injury patients did not appear to respond well to the CVS treatment in a previous study; visceral/abdominal/pelvic pain conditions are outside the scope of this study; purely nociceptive pain is unlikely to respond)
(iii) Somatic symptom disorder with predominant pain (i.e., a primary psychiatric pain disorder) or significant abnormal illness behaviour/non-organic presentation features (psychiatric pain disorders are outside the scope of the study and abnormal illness behaviour features could complicate data interpretation)
(iv) unstable medical condition (e.g. unstable cardiac or respiratory issues) (simple precaution exclusion)
(v) epilepsy (simple precaution exclusion)
(vi) brain injury, other than stroke with central pain being the targeted PP condition (simple precaution exclusion)
(vii) currently pregnant (simple precaution exclusion)
(viii) bipolar disorder, schizophrenia or other psychotic disorder (simple precaution exclusion and theoretical risk of exacerbating mood disorder symptoms)
(ix) significant ear disease in the right ear (or left ear if considering left ear CVS) (avoids risk of worsening any significant ear condition through having water irrigated into the ear canal)

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Not Applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
18/03/2024
Actual
Date of last participant enrolment
Anticipated
18/03/2027
Actual
Date of last data collection
Anticipated
18/09/2027
Actual
Sample size
Target
100
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 41793 0
3168 - Clayton
Recruitment postcode(s) [2] 41792 0
3199 - Frankston

Funding & Sponsors
Funding source category [1] 315471 0
University
Name [1] 315471 0
Monash University
Country [1] 315471 0
Australia
Primary sponsor type
Individual
Name
Dr Steven Miller
Address
26 Innovation Walk, Clayton, VIC, 3800
Country
Australia
Secondary sponsor category [1] 318129 0
Individual
Name [1] 318129 0
Dr Murray Taverner
Address [1] 318129 0
Country [1] 318129 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 314381 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 314381 0
https://www.monash.edu/researchoffice/ethics
Ethics committee country [1] 314381 0
Australia
Date submitted for ethics approval [1] 314381 0
28/11/2023
Approval date [1] 314381 0
06/02/2024
Ethics approval number [1] 314381 0
39650

Summary
Brief summary
We aim to collect data on pain and functional benefits following 6 sessions of caloric vestibular stimulation (CVS) in up to 100 patients with persistent pain (PP). We will gather open label case series data of CVS pain modulation in these PP patients to justify and inform design of a future double blind randomised controlled trial (DB-RCT). We hypothesise that 6 sessions of CVS will induce pain reduction of at least 20% magnitude, for at least 6 weeks duration, in at least 20% of enrolled PP patients. We further hypothesise, based on previous data, that allodynia (pain in response to a non-painful stimulus) will be particularly susceptible to improvement following CVS.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 131374 0
Dr Steven Miller
Address 131374 0
26 Innovation Walk, Clayton, VIC, 3800 (Monash University)
Country 131374 0
Australia
Phone 131374 0
+61 0403 688 841
Fax 131374 0
Email 131374 0
steven.miller@monash.edu
Contact person for public queries
Name 131375 0
Dr Steven Miller
Address 131375 0
26 Innovation Walk, Clayton, VIC, 3800 (Monash University)
Country 131375 0
Australia
Phone 131375 0
+61 0403 688 841
Fax 131375 0
Email 131375 0
steven.miller@monash.edu
Contact person for scientific queries
Name 131376 0
Dr Steven Miller
Address 131376 0
26 Innovation Walk, Clayton, VIC, 3800 (Monash University)
Country 131376 0
Australia
Phone 131376 0
+61 0403 688 841
Fax 131376 0
Email 131376 0
steven.miller@monash.edu

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
All de-identified individual line-by-line data
When will data be available (start and end dates)?
Immediately after publication; no end date determined
Available to whom?
Publicly available
Available for what types of analyses?
Any
How or where can data be obtained?
In a data repository such as those offered by Research Data Australia or Australian Research Data Commons.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.