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Trial registered on ANZCTR


Registration number
ACTRN12620000912987
Ethics application status
Approved
Date submitted
13/07/2020
Date registered
14/09/2020
Date last updated
14/09/2020
Date data sharing statement initially provided
14/09/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Clinical Trial of Perispinal Etanercept Treatment for Stroke patients to examine the effect on fatigue and muscle spasticity.
Scientific title
Placebo-controlled randomized Clinical Trial of Perispinal Etanercept in Australian patients with chronic stroke 2020: Fatigue & muscle spasticity study (PSE-2020).
Secondary ID [1] 301738 0
nil known
Universal Trial Number (UTN)
U1111-1255-1438
Trial acronym
PSE 2020
Linked study record
ACTRN12615001377527 PSE 2020 is a follow up study and the measures used in the current trial builds on the findings of the previous trial.

Health condition
Health condition(s) or problem(s) studied:
Stroke 318194 0
Fatigue 318195 0
Muscle Spasticity 318196 0
Condition category
Condition code
Stroke 316203 316203 0 0
Haemorrhagic
Stroke 316204 316204 0 0
Ischaemic

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Pre-clinical trial screening of participants using Fatigue Assessment Scale (FAS) to select participants who meet the inclusion criteria of FAS >= 35/50 and to establish a baseline SF36 score. Shoulder goniometry will be conducted on the first treatment day.
Intervention drug - Etanercept
Dose Administered: 25 mg
Total duration and frequency of administration, e.g. two doses administered 10-15 days apart;
Mode of administration : Subcutaneous Injection(dorsally above the spine).
Total study duration (including run in screening period): 42 days
Intervention code [1] 318035 0
Treatment: Drugs
Comparator / control treatment
Intervention drug - Normal Saline for injection
Dose Administered: 2 millilitres
Total duration and frequency of administration, e.g. two doses administered 10-15 days apart;
Mode of administration : Subcutaneous Injection(dorsally above the spine).
Total study duration (including run in screening period): 42 days
Control group
Placebo

Outcomes
Primary outcome [1] 324388 0
Shoulder Flexion. Mean change in active shoulder flexion measured in degrees by goniometer
Timepoint [1] 324388 0
Day 1 Pre-treatment
Day 14 post treatment ( Primary)
Primary outcome [2] 324389 0
Fatigue Assessment Score (FAS): Mean change in FAS level out of 50
Timepoint [2] 324389 0
Day minus 14 ( 2 weeks prior to treatment 1)
Day 42 (14 days post- treatment 2)
Secondary outcome [1] 384533 0
Quality of Life - Mean change in SF-36 score
Timepoint [1] 384533 0
.Day minus 14 ( 2 weeks prior to treatment 1)
Day 42 (14 days post- treatment 2)

Eligibility
Key inclusion criteria
1) Stroke that occurred at least 6 months and not more than 15 years prior to screening for this study;
2) Haemorrhagic or ischemic stroke affecting mobility
3) Fatigue Assessment Scale (FAS) score of at least 30 out of 50.
4) Moderate muscle spasticity of the affected arm, with limited range of motion.
5) Participant is able to ambulate at least 5 meters (with or without a cane or walker) without assistance from another individual.
Minimum age
18 Years
Maximum age
70 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1) Aphasia (inability to communicate during testing).
2) Dementia diagnosis prior to date of stroke
3) More than one stroke in the past 3 years
4) Parkinson’s Disease or Parkinsonian symptoms
5) Dementia with Lewy bodies
6) Multiple sclerosis at present or in the past
7) Demyelinating disease at present or in the past
8) History of tuberculosis
9) Positive PPD test or IFN gamma test.
10) HIV infection
11) History of hepatitis B
12) History of deep fungal infection (coccidiodomycosis, histoplasmosis, blastomycosis)
13) Active infection
14) Indwelling urinary catheter
15) Lymphoma, active or in the past
16) Cancer within the past 5 years, non-melanoma skin cancer excluded
17) History of Malignant Melanoma
18) Uncontrolled diabetes mellitus
19) Participants using any immunosuppressive medication, including Kineret (Anakinra) or Abatacept, or glucocorticoids currently
20) Use of a TNF inhibitor (etanercept, infliximab, etc.) in the past
21) Congestive Heart Failure
22) Non-ambulatory
23) Less than two months since hospitalization for any cause
24) Pregnancy or breast-feeding
25) Psychosis or use of anti-psychotic medication (e.g. olanzapine, quetiapine, clozapine, aripiprazole, haloperidol, flupenazine, risperidone, ziprasidone)
26) History of Alcohol abuse within 1 year of study entry
27) Autoimmune disorder
28) Previous neck surgery (such as cervical fusion)
29) Severe or unstable concomitant condition or disease (e.g., known significant neurologic deficit, cancer, hematologic, or coronary disease), or chronic condition (e.g., psychiatric disorder), which, in the opinion of the investigator, would affect the assessment of the safety and tolerability of perispinal Etanercept.
30) Severe aphasia.
31) Participant is not using anti-coagulant (e.g. warfarin, etc.) or anti-platelet drug treatment (e.g. aspirin, etc.) to reduce the risk of ischemic stroke.
32) BMI greater than 40.
33) Grand mal seizure within 3 months of study enrolment.
34) Participant has received any investigational drug within 30d before screening, or is scheduled to receive an investigational drug, other than the blinded-study drug during the course of this study.

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)
Central randomisation by computer. This will only be provided to the trial pharmacist to retain securely and confidentially in his possession as the unblinding code to be used in assigning participants to either group as they are enrolled into the study.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
These numbers will be assigned and retained only by the trial pharmacist who will use a computer based random number generator, in a blinded manner to all trial investigators to establish the trial unblinding code for random assignment of enrolled participants into the ACTIVE DRUG or PLACEBO CONTROL Group (to a total of up to 40 participants in each arms). This will only be provided to the trial pharmacist to retain securely and confidentially in his possession as the unblinding code to be used in assigning participants to either group as they are enrolled into the study.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Efficacy
Statistical methods / analysis
The sample size of 40 participants per group 1 and 2, and 80 completed participants on trial with 40 in each study arm (20 PLACEBO and 20 ACTIVE participants) per group is based on the published data from the Phase I trial [ Ralph, Weissenberger, Bonev, King, Bonham, Ferguson, Smith,Goodman-Jones, & Espinet, 2020]. The assumption is that the population of participants is normally distributed. The quantitative measurement software used was that developed by Dr David Schoenfeld (dschoenfeld@partners.org) at the Harvard website http://hedwig.mgh.harvard.edu/sample_size/js/js_parallel_quant.html and was validated by our trial biostatistician. For the outcomes used in this study, power calculations can be made as follows.
Power calculation based on previous analyses and first clinical trial outcomes.
The values used for study power calculation are taken from those reported previously in the first clinical trial where by UNIANOVA a significantly improved shoulder flexion from baseline to after second treatment, at visit 2 was obtained (p = 0.011, measure of effect size = 0.28, observed power of 76%). Hence, the power of our study based on previous data from improvements in mobility score analysis is approaching 80% with only 20 patients. Using the power calculation tool, a total of 38 patients will be required in this two-treatment parallel-design study such that the probability is 81 percent that the study will detect a treatment difference at a two-sided 0.05 significance level, if the true difference between treatments is 55.000 units. This is based on the assumption that the standard deviation of the response variable is high at 58. Therefore, a 40-80 patient study should be more than adequately empowered.
Reference: Ralph, S. J., Weissenberger, A., Bonev, V., King, L. D., Bonham, M. D., Ferguson, S., Smith, A.D.,Goodman-Jones, A.A., & Espinet, A. J. (2020). Phase I/II parallel double-blind randomized controlled clinical trial of perispinal etanercept for chronic stroke: improved mobility and pain alleviation. Expert Opinion on Investigational Drugs, 1-16.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,NT,QLD,SA,TAS,WA,VIC

Funding & Sponsors
Funding source category [1] 306172 0
University
Name [1] 306172 0
Griffith University
Address [1] 306172 0
1 Parklands Drive,
Southport QLD 4215
Country [1] 306172 0
Australia
Primary sponsor type
University
Name
Griffith University
Address
1 Parklands Drive,
Southport QLD 4215
Country
Australia
Secondary sponsor category [1] 306643 0
Charities/Societies/Foundations
Name [1] 306643 0
Stroke Recovery Trial Fund LTD
Address [1] 306643 0
21 Russell St,
Toowoomba City QLD 4350
Country [1] 306643 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 306384 0
Griffith University HREC
Ethics committee address [1] 306384 0
1 Parklands Dr, Southport QLD 4215
Ethics committee country [1] 306384 0
Australia
Date submitted for ethics approval [1] 306384 0
16/01/2020
Approval date [1] 306384 0
07/09/2020
Ethics approval number [1] 306384 0
2020/131

Summary
Brief summary
1 in 6 Australians will have a stroke. Other than acute and supportive rehabilitative care – there is no effective treatment for chronic stroke. When brain tissue is damaged, the area around the dead area undergoes a long-term neuro-inflammatory process effectively shutting down the function of the area and extending the originally damaged area. By injecting an anti-inflammatory biologic medication currently used to treat Rheumatoid arthritis by a novel route to bypass the blood brain barrier with 2 doses, 2 weeks apart, it is proposed that this neuroinflammation will be reduced and some associated function regained. PSE 2020 will extend on the data from a recently published world-first RCT conducted by Griffith University School of Medical Science.
Trial website
https://www.griffith.edu.au/menzies-health-institute-queensland/our-research/clinical-trials/stroke Needs to be updated once full GUHREC approval is finalized
Trial related presentations / publications

Public notes

Contacts
Principal investigator
Name 103698 0
A/Prof Stephen Ralph
Address 103698 0
G12 2.07,
Griffith University
Gold Coast Campus
1 Parklands Dr, Southport QLD 4215
Country 103698 0
Australia
Phone 103698 0
+61755528583
Fax 103698 0
Email 103698 0
s.ralph@griffith.edu.au
Contact person for public queries
Name 103699 0
A/Prof Coralie Graham
Address 103699 0
School of Nursing & Midwifery
University of Southern Queensland
West Street
Toowoomba, 4350 Queensland
Country 103699 0
Australia
Phone 103699 0
+61746312934
Fax 103699 0
Email 103699 0
coralie.graham@usq.edu.au
Contact person for scientific queries
Name 103700 0
A/Prof Stephen Ralph
Address 103700 0
G12 2.07,
Griffith University
Gold Coast Campus
1 Parklands Dr, Southport QLD 4215
Country 103700 0
Australia
Phone 103700 0
+61755528583
Fax 103700 0
Email 103700 0
s.ralph@griffith.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Primary outcome measures
When will data be available (start and end dates)?
Data will be available on request from two years post publication of the clinical trail which is anticipated to be from February 2023.
Available to whom?
Available on request by medical researchers
Available for what types of analyses?
Appropriate data/ meta analysis
How or where can data be obtained?
Clinical trial data requests can be made by email to PI Associate Professor Stephen Ralph s.ralph@griffith.edu.au
What supporting documents are/will be available?
No other documents available
Summary results
No Results