Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000479707
Ethics application status
Approved
Date submitted
22/03/2022
Date registered
25/03/2022
Date last updated
13/04/2024
Date data sharing statement initially provided
25/03/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Human response to neck treatment following concussion
Scientific title
Autonomic nervous system and endocrine system response to upper or lower cervical spine mobilization in males with persistent post-concussion symptoms: a proof-of-concept trial
Secondary ID [1] 306727 0
None
Universal Trial Number (UTN)
U1111-1276-1021
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Persistent post-concussion symptoms
 325724 0
Condition category
Condition code
Physical Medicine / Rehabilitation 323068 323068 0 0
Physiotherapy
Neurological 323115 323115 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Cervical spine mobilization manual therapy technique
-Parallel arm 1-Upper cervical spine mobilization applied to C0-1 and C1-2 for 3 lots of 2 minutes each, separated by a 30 second rest.
-Parallel arm 2-Lower cervical spine mobilization applied to C6-7 and C7-T1 for 3 lots of 2 minutes each, separated by a 30 second rest.
Each mobilization will be low frequency, mid-range, bilateral and alternating oscillations.
All interventions will be performed by the same operator (New Zealand registered physiotherapist with a Masters degree in orthopaedic manipulative therapy), face to face, and on an individual basis.
Each participant will be randomised to either arm 1 (upper cervical mobilization) or arm 2 (lower cervical mobilization).
Each intervention will be held in the same room at the School of Physiotherapy, University of Otago, Dunedin, New Zealand.
This trial is performing a one-off intervention. If a participant does not attend their intervention session, their data will not be included. Therefore, monitoring adherence to the intervention is not applicable.
Intervention code [1] 323181 0
Treatment: Other
Comparator / control treatment
Active control. A comparison is being made between upper cervical mobilization (arm 1) and lower cervical mobilization (arm 2). There is no reference comparator as we are investigating the different response between each mobilization.
Control group
Active

Outcomes
Primary outcome [1] 330833 0
Difference in salivary cortisol levels measured with the unstimulated passive drool salivary sample technique
Timepoint [1] 330833 0
Night (2200-0000) post-intervention
Secondary outcome [1] 407780 0
-Difference in salivary cortisol levels measured with the unstimulated passive drool salivary sample technique
Timepoint [1] 407780 0
-Cortisol-5 minutes post-intervention, 30 minutes post-intervention
Secondary outcome [2] 407781 0
-Difference in heart rate variability (rMSSD-specific index we are using for secondary analysis) measured with Camera HRV smart phone application
Timepoint [2] 407781 0
-Heart rate variability (rMSSD)-5 minutes post-intervention, 30 minutes post-intervention, morning (0600-0800) post-intervention

Eligibility
Key inclusion criteria
Males with a diagnosis of persistent post-concussion symptoms aged between 19-35 years old who own an iPhone.
Minimum age
19 Years
Maximum age
35 Years
Sex
Males
Can healthy volunteers participate?
No
Key exclusion criteria
Participants will be excluded if they are:
-Asymptomatic.
-Unable to refrain from external treatment (treatment session in person or online) or change in treatment (progression or modification of existing treatment) for three consecutive days, specifically days five to seven (out of eight), so the intervention can be performed, and salivary samples collected (primary outcome).
-Confounding factors to the outcome measurements. These include; Serious medical or psychiatric disorder; co-morbid musculoskeletal or serious conditions which may confound treatment or anticipated recovery; NSAIDs use; recent steroid injections; currently have an endocrine, central nervous system, cardiovascular, or a mental health disorder; systemic glucocorticoid or cardioactive medication; serotonin-norepinephrine reuptake inhibitors; moderate to severe traumatic brain injury. Note, Participants prescribed with psychotropic medication for treatment of concussion-related symptoms (e.g., headache and migraine) will be permitted to be enrolled in the study provided they are not prescribed serotonin-norepinephrine reuptake inhibitors (e.g., desvenlafaxine, venlafaxine, duloxetine, etc.) given their impact on autonomic function.
-Contra-indications to the intervention. If any precautions to manual therapy are present, participants will be excluded on a case-by-case basis.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Sealed opaque envelopes will be used for allocation concealment. At the enrolment appointment, each participant will be block randomised by use of sealed opaque envelopes to individually code the saliva collection vials with their participation number. Both the researcher and participant will not be aware which group (arm 1 or arm 2) they are in at the enrolment appointment.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created from computer software will be used to determine treatment allocation, at a 1:1 ratio, using a block length of six. An independent research assistant will provide the clinician performing the intervention with the randomisation table, linking the participant number (generated by sealed opaque envelopes at the enrolment appointment) with the participants group (arm 1 or arm 2).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
We have consulted with a biostatistician in the planning/development of this trial.
-Power analysis
Budget restraints have placed a ceiling on the maximum sample size able to be recruited. Considering the funding we have available, we will aim to recruit a maximum sample size of n = 30 with n = 15 (1:1 ratio) in each arm of the parallel design RCT. The backwards, ‘participants I can get’ approach to sample size calculation is reported to be an acceptable method in proof of concept studies (Ting et al., 2017; Verhagen & Yu, 2021).
-Statistical analysis
Each participant will undergo repeated measures. Therefore, outcomes are non-independent of each other. To explicitly account for correlations between repeated measures, and to answer the research question, we will use a mixed model approach (Detry & Ma, 2016) as our statistical test. The primary statistic of interest will be the treatment group x time interaction. The primary outcome will be sCOR at the night post-intervention. As we have a single primary outcome, there is no need to adjust for multiplicity (Li et al., 2016). The secondary outcomes are considered exploratory. Incomplete data is common in longitudinal studies with repeated measures caused by participants missing appointments, missing measurements, or dropping out. Due to this, participants may have different numbers of available data. Unlike repeated measures analysis of variance, mixed models can accommodate this and use all available observations and patients in the analysis (Detry & Ma, 2016).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
13/05/2022
Actual
24/05/2022
Date of last participant enrolment
Anticipated
31/03/2023
Actual
29/03/2023
Date of last data collection
Anticipated
8/04/2023
Actual
8/04/2023
Sample size
Target
30
Accrual to date
Final
19
Recruitment outside Australia
Country [1] 24681 0
New Zealand
State/province [1] 24681 0
Otago

Funding & Sponsors
Funding source category [1] 311058 0
University
Name [1] 311058 0
University of Otago (The Stanley Paris PhD OMT Scholarship research costs)
Country [1] 311058 0
New Zealand
Funding source category [2] 311073 0
University
Name [2] 311073 0
School of Physiotherapy (Mark Steptoe Memorial Trust fund)
Country [2] 311073 0
New Zealand
Funding source category [3] 311074 0
University
Name [3] 311074 0
School of Physiotherapy (School of Physiotherapy PhD fund)
Country [3] 311074 0
New Zealand
Primary sponsor type
Individual
Name
Gerard Farrell
Address
Centre for Health, Activity, and Rehabilitation Research, School of Physiotherapy, University of Otago, 325 Great King Street, North Dunedin, Dunedin 9016
Country
New Zealand
Secondary sponsor category [1] 312387 0
Individual
Name [1] 312387 0
Steve Tumilty
Address [1] 312387 0
Centre for Health, Activity, and Rehabilitation Research, School of Physiotherapy, University of Otago, 325 Great King Street, North Dunedin, Dunedin 9016
Country [1] 312387 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 310603 0
Southern Health and Disability Ethics Committee
Ethics committee address [1] 310603 0
Ethics committee country [1] 310603 0
New Zealand
Date submitted for ethics approval [1] 310603 0
31/03/2022
Approval date [1] 310603 0
12/05/2022
Ethics approval number [1] 310603 0
2022 EXP 12201

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 118230 0
A/Prof Steve Tumilty
Address 118230 0
Centre for Health, Activity, and Rehabilitation Research School of Physiotherapy University of Otago 325 Great King Street North Dunedin Dunedin, 9016
Country 118230 0
New Zealand
Phone 118230 0
+64 3 479 7193
Fax 118230 0
Email 118230 0
[email protected]
Contact person for public queries
Name 118231 0
Gerard Farrell
Address 118231 0
Centre for Health, Activity, and Rehabilitation Research School of Physiotherapy University of Otago 325 Great King Street North Dunedin Dunedin, 9016
Country 118231 0
New Zealand
Phone 118231 0
+64 3 479 7460
Fax 118231 0
Email 118231 0
[email protected]
Contact person for scientific queries
Name 118232 0
Gerard Farrell
Address 118232 0
Centre for Health, Activity, and Rehabilitation Research School of Physiotherapy University of Otago 325 Great King Street North Dunedin Dunedin, 9016
Country 118232 0
New Zealand
Phone 118232 0
+64 3 479 7460
Fax 118232 0
Email 118232 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Following de-identification, individual participant data underlying the published results only.
When will data be available (start and end dates)?
Immediately following publication. There is no end date.
Available to whom?
Only researchers who provide a methodologically sound proposal with the relevant ethical board approval.
Available for what types of analyses?
The data will be available only to achieve the aims of the approved proposal and to provide de-identified details regarding the participants. Researchers who have access to the full text publication will be able to use the data for a meta-analysis if applicable.
How or where can data be obtained?
Raw data will be made available on request. This request can be made to the lead investigator, Gerard Farrell, by email ([email protected]). Depending upon the journal that accepts this work for publication, the raw data may be made available as an appendix file.


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.