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Trial registered on ANZCTR


Registration number
ACTRN12618000162213
Ethics application status
Approved
Date submitted
11/01/2018
Date registered
2/02/2018
Date last updated
30/06/2021
Date data sharing statement initially provided
30/06/2021
Date results information initially provided
30/06/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Measuring skin and tissue change before and after compression: a comparative study of people with and without primary lymphoedema
Scientific title
Dermal composition and related measures: response to pneumatic compression in people with and without primary lymphoedema.
Secondary ID [1] 293666 0
None
Universal Trial Number (UTN)
U1111-1206-9482
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Primary lymphoedema 305967 0
Condition category
Condition code
Cardiovascular 305161 305161 0 0
Diseases of the vasculature and circulation including the lymphatic system
Physical Medicine / Rehabilitation 305162 305162 0 0
Physiotherapy
Skin 305325 305325 0 0
Normal skin development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intermittent pneumatic compression (IPC) will be applied to either an upper or lower limb with lymphoedema in one session only. (Limb treated will be that with most severe lymphoedema; in case of control, the site corresponding to the matched lymphoedema participant.) Device used is a MediRent LX9 with sequential pneumatic pressure applied only to the limb (to axilla in the upper limb (UL) or top of thigh in the lower limb (LL)). Number of cells per sleeve and timing of pressure cycle will be according to the LX9. The dose will be 40mmHg for UL and 60mmHg for LL over 50 minutes; children under 9 years will have 30 mmHg (UL) and 40 mmHg for (LL) over 30 minutes. IPC will be administered by the principal investigator, a physiotherapist.
Adherence will not be assessed; study period is one treatment/ attendance.
Intervention code [1] 299934 0
Treatment: Devices
Comparator / control treatment
Intermittent pneumatic compression (IPC) will be applied to people with no lymphoedema, age and gender matched to a lymphoedema participant for comparison of their response to IPC.
Control group
Active

Outcomes
Primary outcome [1] 304312 0
Dermal depth as assessed with high frequency ultrasound using the DermaScan C of frequency 20MHz. Two points will be measured on both the affected (treated) and contra-lateral untreated limb. These two points-the foot and the calf- on both limbs will be used for assessment for each outcome.
Timepoint [1] 304312 0
Before and after one application of intermittent pneumatic compression (IPC).
Primary outcome [2] 304313 0
Fluid component of the skin assessed using a DermaScan C high frequency ultrasound (frequency of 20MHz). A scale from 0 - 255 represents the full range of intensity of echoes seen in B-scan mode: the component of the image that relates to fluid (low intensity) will be represented by the range of 0-30.
Timepoint [2] 304313 0
Before and after one application of IPC.
Secondary outcome [1] 341556 0
Skin resistance assessed using the Indurometer BME 1563G, a tonometer developed by Flinders University.
Timepoint [1] 341556 0
Before and after one application of IPC.
Secondary outcome [2] 341557 0
Bioimpedance spectroscopy assessed using an Impedimed device (SFB7).
Timepoint [2] 341557 0
Before and after one application of IPC.
Secondary outcome [3] 341558 0
Limb circumference of the affected and unaffected limb (treated and non-treated limb). Circumferences will be taken at a point where the high frequency ultrasound (HFU) is to be applied and at a clinically relevant point for each limb.
Timepoint [3] 341558 0
Before and after one application of IPC.
Secondary outcome [4] 341559 0
A measure of skin moisture (tissue dialectric constant), as measured by the MoistureMeterD manufactured by Delfin Technologies. This will be measured at three points on both the limb to be treated and the limb not treated.
Timepoint [4] 341559 0
Before and after one application of IPC

Eligibility
Key inclusion criteria
People with primary lymphoedema and people without primary lymphoedema age and gender matched to those with primary lymphoedema.
Minimum age
3 Years
Maximum age
40 Years
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Exclusion from study if have any of the below:
• Have had any skin infection (cellulitis) within previous two months
• Have a diagnosed connective tissue disorder e.g. lipodermatosclerosis or local occurrence of a skin condition such as psoriasis;
• Have a congenital condition which affects the skin such as Ehlers-Danlos Syndrome or Marfan's Disease
Exclusions for Intermittent Pneumatic Compression- will be excluded from the study:
• a. Active metastatic disease
• b. Known or suspected deep venous thrombosis
• c. Pulmonary embolism
• d. Thrombophlebitis
• e. Uncontrolled cardiac failure
• f. Current cellulitis
• g. Pulmonary oedema
• h. Ischaemic vascular disease
• i. Severe peripheral neuropathy
• j. Chronic regional pain syndrome
Exclusions for bioimpedance spectroscopy only (will participate in all other parts of the study except for bioimpedance):
• a. Are pregnant
• b. Have a pacemaker or other implanted electronic device
• c. Have a metal implant such as pins or plates in bones

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?



The people analysing the results/data
Intervention assignment
Other
Other design features
The same intervention is applied to both groups in this study. The difference between groups is inherent to the group (lymphoedema or no lymphoedema). So all receive the same intervention and the difference in response will be investigated.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Sample size will be re-evaluated after measurement of 10 people in the pilot. Numbers of people with primary lymphoedema are low: while sample size estimate is 100 participants, with 50 per group involving recruitment over three states, the sample size will be determined by numbers of people with primary lymphoedema within the age and inclusion criteria available to participate.
Statistical Methods:
1. Comparative data, including mean, median, standard deviation and range will be described for all measures of dermal and soft tissue properties and, for within group analysis will be sub-grouped for age and gender, as Non lymphoedema (NLO) and primary lympheodema (PLO) are matched across groups. As numbers at each age may be small, the effect of age will also be investigated by groups of ages: e.g. children from 3-4 years and from 5-9 years, adolescents from 10-18 years and adults 19-40 years. HFU images will be investigated for intra-rater reliability.
2. Comparative measures will be investigated for significant difference within those with lymphoedema (within group PLO), stratified by age and duration of lymphoedema.
3. Comparative measures will be investigated for significant difference between study groups matched by age, gender and limb dominance and stratified for ethnicity. Matching of the PLO group with a NLO control group by age, gender and limb dominance will offset the relatively low numbers in each age and control for effect of limb dominance in volume measures.
4. The convergence validity of clinical assessment tools:
• Circumference measures (at point of interest).
• Bioimpedance,
• MoistureMeter,
• Indurometer
will be investigated, in measures of agreement with dermal changes as identified with HFU, utilising SPSS.

Recruitment
Recruitment status
Completed
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)
NSW,VIC
Recruitment hospital [1] 9638 0
The Royal Childrens Hospital - Parkville
Recruitment hospital [2] 9639 0
Mercy Hospital for Women - Heidelberg
Recruitment hospital [3] 9641 0
Mt Wilga Private Hospital - Hornsby
Recruitment postcode(s) [1] 18400 0
3052 - Parkville
Recruitment postcode(s) [2] 18401 0
3084 - Heidelberg
Recruitment postcode(s) [3] 18403 0
2077 - Hornsby

Funding & Sponsors
Funding source category [1] 298287 0
University
Name [1] 298287 0
Flinders University
Address [1] 298287 0
Sturt Rd,
Bedford Park
South Australia SA 5042
Country [1] 298287 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Rd
Bedford Park
SA 5042
Country
Australia
Secondary sponsor category [1] 297402 0
Other
Name [1] 297402 0
Murdoch Children's Research Institute
Address [1] 297402 0
Murdoch Children's Research Institute
50 Flemington Road
Parkville
VIC 3052
Country [1] 297402 0
Australia
Secondary sponsor category [2] 297631 0
Charities/Societies/Foundations
Name [2] 297631 0
Rotary Health
Address [2] 297631 0
2nd Floor, 43 Hunter Street,
Parramatta NSW 2150

Postal Address
PO Box 3455,
Parramatta NSW 2124
Country [2] 297631 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299286 0
The Royal Childrens Hospital Melbourne HREC
Ethics committee address [1] 299286 0
The Royal Childrens Hospital Melbourne
50 Flemington Road Parkville Victoria 3052
Ethics committee country [1] 299286 0
Australia
Date submitted for ethics approval [1] 299286 0
30/09/2016
Approval date [1] 299286 0
19/12/2016
Ethics approval number [1] 299286 0
HREC/16/RCHM/136
Ethics committee name [2] 299291 0
Mercy Health Human Research Ethics Committee
Ethics committee address [2] 299291 0
Mercy Hospital for Women
163 Studley Road
Heidelberg, VIC 3084
Ethics committee country [2] 299291 0
Australia
Date submitted for ethics approval [2] 299291 0
06/10/2016
Approval date [2] 299291 0
21/02/2017
Ethics approval number [2] 299291 0
R16/67

Summary
Brief summary
Primary lymphoedema occurs in people with a genetic predisposition and manifests as long-term swelling of a body part. Current assessments provide little understanding of the composition of the underlying tissues and how they respond to treatments. No information has been available about the difference between those with and without lymphoedema with respect to age and skin properties.
This study will use high frequency ultrasound (HFU) to investigate differences in skin composition and thickness in people with and without primary lymphoedema. The measures to be used include clinical tools which measure dermal properties (skin resistance and elasticity, and measures of water content and limb volume). The response of the skin to compression, a standard lymphoedema intervention, will then be assessed with HFU and clinical assessment tools, following the application of intermittent pneumatic compression.
Children and adults with and without primary lymphoedema, aged between three and 40 years old, will be included.
Analysis of clinical tools for a measure of equivalence with HFU findings will inform the use of clinical tools and enable translation of study findings to the clinical setting. Compression is used in healthy populations to support limbs during travel and sport: inclusion in this study of both the healthy population and the understudied childhood lymphoedema population will add to the understanding of the effect of compression on the skin for all groups and form the basis for targeted treatment guidelines. Most lymphoedema research has investigated secondary lymphoedema, despite there being strong growing evidence of underlying genetic predisposition or covert primary lymphoedema in those who develop secondary lymphoedema.
The findings of this study will provide a basis for understanding the progression of primary lymphoedema and inform future primary and secondary lymphoedema research.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 2337 2337 0 0
Attachments [2] 2341 2341 0 0
Attachments [3] 2342 2342 0 0
Attachments [4] 2343 2343 0 0
/AnzctrAttachments/374214-Master_Adult PICF_lymphoedema_v3_10102017.pdf (Participant information/consent)
Attachments [5] 2344 2344 0 0
/AnzctrAttachments/374214-Master_Adult Non_LO_PICF_v3_10102017.pdf (Participant information/consent)
Attachments [6] 2345 2345 0 0
Attachments [7] 2346 2346 0 0
/AnzctrAttachments/374214-Master_ParentGuardian_NonLO_PICF v2 03102017.pdf (Participant information/consent)

Contacts
Principal investigator
Name 79914 0
Ms Jane Phillips
Address 79914 0
Murdoch Childrens Research Institute
50 Flemington Rd
Parkville Vic 3052
Country 79914 0
Australia
Phone 79914 0
+61 418 104 690
Fax 79914 0
Email 79914 0
jane.phillips@flinders.edu.au
Contact person for public queries
Name 79915 0
Ms Jane Phillips
Address 79915 0
Murdoch Childrens Research Institute
50 Flemington Rd
Parkville Vic 3052
Country 79915 0
Australia
Phone 79915 0
+61 418 104 690
Fax 79915 0
Email 79915 0
jane.phillips@flinders.edu.au
Contact person for scientific queries
Name 79916 0
Ms Jane Phillips
Address 79916 0
Murdoch Childrens Research Institute
50 Flemington Rd
Parkville Vic 3052
Country 79916 0
Australia
Phone 79916 0
+61 418 104 690
Fax 79916 0
Email 79916 0
jane.phillips@flinders.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
What supporting documents are/will be available?
Ethical approval
How or where can supporting documents be obtained?
Type [1] 12371 0
Ethical approval
Citation [1] 12371 0
Link [1] 12371 0
Email [1] 12371 0
Other [1] 12371 0
Summary results
Have study results been published in a peer-reviewed journal?
Yes
Journal publication details
Publication date and citation/details [1] 12372 0
Phillips J, Reynolds KJ, Gordon SJ. Dermal thickness and echogenicity using DermaScan C high frequency ultrasound: Methodology and reliability testing in people with and without primary lymphoedema. Skin Research and Technology. 2020.
Attachments [1] 12372 0
Other publications
Have study results been made publicly available in another format?
No
Results – basic reporting
Results – plain English summary