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Trial registered on ANZCTR


Registration number
ACTRN12624001411538
Ethics application status
Approved
Date submitted
13/11/2024
Date registered
29/11/2024
Date last updated
29/11/2024
Date data sharing statement initially provided
29/11/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
Plasmapheresis for Treatment Refractory Postural Orthostatic Tachycardia Syndrome
Scientific title
Impact of Plasmapheresis on Autonomic Symptom Burden in those living with treatment refractory Postural Orthostatic Tachycardia Syndrome
Secondary ID [1] 311989 0
None
Universal Trial Number (UTN)
Trial acronym
PLEX POTS
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Postural Orthostatic Tachycardia Syndrome 333604 0
Condition category
Condition code
Neurological 330289 330289 0 0
Other neurological disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention under investigation is plasmapheresis. This is a procedure in which plasma is separated and removed from blood and will be replaced by albumin. This is undertaken by an apheresis machine in a hospital setting, under the care of specialist health care providers. The procedure is undertaken by intravenous access, either through a central or peripheral catheter. The volume of plasma removed is based on the total blood volume (TBV) of each participant. This differs for every person and is based off Nadler's formula which account for the participant's height, weight and sex and also utilised haemotcrit to calculate TBV. The volume removed is similar to replacement fluid volume after accounting for citrate infusion. Fluid balance at the completion of each session is equal to baseline values. Each session is expected to take 3-4 hours, accounting for establishing vascular access. The frequency of sessions will be as follows: four times over a two week period and then fortnightly over a ten week period. At the end of this period, participants will complete the Composite Autonomic Symptom Score (COMPASS-31) questionnaire, with those demonstrating an improvement of 10 points or greater on this questionnaire compared to their baseline values proceeding to a further four sessions of plasmapheresis occurring once every three weeks. Adherence to the intervention will be assessed by medical record review.
Intervention code [1] 328450 0
Treatment: Other
Comparator / control treatment
The comparative treatment is intravenous fluids which will be administered by peripheral catheter. One litre of Hartmann's solution will be administered at the same frequency as plasmapheresis sessions, as outlined in the intervention arm description.
Control group
Active

Outcomes
Primary outcome [1] 338031 0
Autonomic symptom burden
Timepoint [1] 338031 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention (primary timepoint).
Secondary outcome [1] 434197 0
Functional capacity and disability
Timepoint [1] 434197 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention
Secondary outcome [2] 434198 0
Health related quality of life
Timepoint [2] 434198 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [3] 434199 0
Gastrointestinal symptom burden
Timepoint [3] 434199 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [4] 434200 0
Fatigue
Timepoint [4] 434200 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [5] 434201 0
Anxiety score
Timepoint [5] 434201 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [6] 434202 0
Postural Orthostatic Tachycardia Syndrome (POTS) symptom burden
Timepoint [6] 434202 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [7] 434203 0
Cognitive function
Timepoint [7] 434203 0
Baseline and 6 months post commencement of the intervention
Secondary outcome [8] 434204 0
Autonomic testing parameters
Timepoint [8] 434204 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [9] 434205 0
Sudomotor function
Timepoint [9] 434205 0
Baseline and at six months post commencement of the intervention
Secondary outcome [10] 434206 0
Blood test markers for autoimmunity including ANA, cardiolipin and Beta 2 Glycoprotein antibodies, ENA panel.
Timepoint [10] 434206 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [11] 442064 0
Depression score
Timepoint [11] 442064 0
Baseline, 3 months post commencement of the intervention and 6 months post commencement of the intervention.
Secondary outcome [12] 442382 0
Blood markers for inflammation including high sensitivity CRP, IL-1, IL-6 and IL-17 cytokines
Timepoint [12] 442382 0
Baseline, 2 weeks post commencement of the intervention, 3 months post commencement of the intervention and 6 months post commencement of the intervention.

Eligibility
Key inclusion criteria
1. Confirmed POTS diagnosis as per standard criteria with lifestyle adjustments [adequate fluid intake, increased salt intake, use of compression wear if tolerated and exercise physiology attendance] and pharmacological treatments trialled for at least 12 months;
2. Evidence of autoimmunity. This is defined as [A]: ANA titre of greater than 1:360; or [B]: greater than or equal to 1 comorbid autoimmune condition; or [C]: two first degree relatives with autoimmune conditions; or [D]: presence of other autoimmune antibodies;
3. Participants must also demonstrate at least one related symptom from three of the following areas below: [A] Severe gastrointestinal dysfunction including gastroparesis, weight loss and/or Gastroparesis Cardinal Symptom Index Score greater than or equal to 2; [B] Neurocognitive impairment e.g., new onset attention deficit hyperactivity disorder, refractory migraine or headache; [C] Bladder symptoms e.g., overactive, or neurogenic bladder, frequent urinary tract infections, nocturia; [D] Significant fatigue, defined as Fatigue Severity Scale score greater than 36/63; [E] evidence of moderately or severely reduced sudomotor function in at least two peripheral sites OR reduced small nerve fibre density on biopsy.
4. Evidence of functional incapacity e.g., unable to attend work or education
5. Ambulant to a level suitable for management in a hospital outpatient department
6. Greater than or equal to 18 years of age.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable to provide informed consent;
2. Unable to attend hospital for plasmapheresis;
3. Unable attend baseline tests and study follow-ups;
4. Current treatment with any Immunosuppressant medications within 1-month prior to randomisation;
5. Pregnant or planning to become pregnant during the expected study duration;
6. Suffers from severe mental health disorders where apheresis may compromise medication management of these conditions.

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)
Randomisation will occur within a Research Electronic Data Capture (REDCap) database
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Randomisation will occur in a 1:1 fashion with randomly permuted blocks of 4 to 6.
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
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
2/12/2024
Actual
Date of last participant enrolment
Anticipated
1/06/2027
Actual
Date of last data collection
Anticipated
1/12/2027
Actual
Sample size
Target
28
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 316337 0
Charities/Societies/Foundations
Name [1] 316337 0
Dysautonomia International
Country [1] 316337 0
United States of America
Primary sponsor type
University
Name
The University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 318522 0
Hospital
Name [1] 318522 0
Royal Adelaide Hospital
Address [1] 318522 0
Country [1] 318522 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315147 0
Central Adelaide Local Health Network HREC
Ethics committee address [1] 315147 0
Ethics committee country [1] 315147 0
Australia
Date submitted for ethics approval [1] 315147 0
12/04/2024
Approval date [1] 315147 0
25/07/2024
Ethics approval number [1] 315147 0
2023/HRE00220
Ethics committee name [2] 315150 0
University of Adelaide Human Research Ethics Committee
Ethics committee address [2] 315150 0
Ethics committee country [2] 315150 0
Australia
Date submitted for ethics approval [2] 315150 0
20/05/2024
Approval date [2] 315150 0
25/09/2024
Ethics approval number [2] 315150 0

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

Contacts
Principal investigator
Name 133818 0
Prof Dennis Lau
Address 133818 0
South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, 5000, Australia
Country 133818 0
Australia
Phone 133818 0
+61 8 8128 4277
Fax 133818 0
Email 133818 0
dennis.lau@adelaide.edu.au
Contact person for public queries
Name 133819 0
Celine Gallagher
Address 133819 0
South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, 5000, Australia
Country 133819 0
Australia
Phone 133819 0
+61 8 8128 4277
Fax 133819 0
Email 133819 0
celine.gallagher@adelaide.edu.au
Contact person for scientific queries
Name 133820 0
Celine Gallagher
Address 133820 0
South Australian Health and Medical Research Institute, North Terrace, Adelaide, South Australia, 5000, Australia
Country 133820 0
Australia
Phone 133820 0
+61 8 8128 4277
Fax 133820 0
Email 133820 0
celine.gallagher@adelaide.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?
Deidentified data on study outcomes will be available.
When will data be available (start and end dates)?
Data will be available from six months after the publication of the main results for a period of 5 years.
Available to whom?
Data will be available to other researchers who propose a proposal that is deemed satisfactory by the Steering Committee of this trial.
Available for what types of analyses?
Data will only be made available for the purposes outlined in study proposals or for individual participant data as part of meta analyses.
How or where can data be obtained?
From the principal investigator who can be contacted at dennis.lau@adelaide.edu.au.


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.