Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12624000950561
Ethics application status
Approved
Date submitted
2/07/2024
Date registered
5/08/2024
Date last updated
17/11/2024
Date data sharing statement initially provided
5/08/2024
Type of registration
Prospectively registered

Titles & IDs
Public title
The EndoChill Trial: Evaluating the safety and efficacy of the Wim Hof Method for endometriosis pain
Scientific title
A single case experimental design trial evaluating the efficacy and safety of the Wim Hof Method for systemic inflammation and pain in people with endometriosis
Secondary ID [1] 312435 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Endometriosis 334257 0
Endometriosis-associated pain 334258 0
Condition category
Condition code
Alternative and Complementary Medicine 330921 330921 0 0
Other alternative and complementary medicine
Reproductive Health and Childbirth 331004 331004 0 0
Other reproductive health and childbirth disorders
Reproductive Health and Childbirth 331005 331005 0 0
Menstruation and menopause

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Once enrolled into the study, participants will follow a three-phase study procedure (baseline, intervention, and follow-up) which will entail the following:

Baseline Phase:

Participants will undergo an eTVUS (transvaginal ultrasound for endometriosis) scan to establish their initial endometriosis lesion characteristics. This will form part of the inclusion and exclusion criteria with only participants that have endometriosis lesions visible by eTVUS included in the study.

Participants will complete daily pelvic pain ratings for the duration of the study, specifically using an 11-point numerical rating scale (NRS) via the Ethica app on their mobile device.

A second eTVUS will be completed in the week prior to the intervention phase. A blood sample will be collected on the same day as the second eTVUS to assess sympathetic nervous system function, hormone levels, and innate immune responses. Participants will also complete the Pelvic Pain Impact Questionnaire (PPIQ) and Pelvic Pain Psychological Screening Questionnaire (3PSQ) using the Ethica App. These questionnaires will be used to measure physical and psychological impacts of pain associated with endometriosis.

The baseline phase of the study will vary in length from 1 to 6 weeks based upon participant randomisation.

Intervention Phase:

The Wim Hof Method (WHM) is a novel intervention that combines breathing exercises, mindfulness, and cold exposure therapy to improve health outcomes.

At the beginning of the intervention phase, participants will attend (in small groups of 4 to 6 people) one training workshop introducing the WHM, including correct technique and safety requirements (3 hours duration). These workshops will be conducted by a trained instructor.

Participants will then continue to practice the WHM daily at home for 12 weeks, guided and recorded via the WHM app. In addition, participants will have the option to attend up to 2 x 1-hour supervised WHM sessions per week during the intervention phase.

During intervention weeks 6 (mid-intervention) and 12 (end-intervention), participants will attend a supervised WHM session. A blood sample will be collected on each of these visits to assess sympathetic nervous system function, hormone levels, and innate immune responses. Participants will also complete the PPIQ and 3PSQ.

Participants will continue recording daily pelvic pain ratings via the Ethica app.

Follow-up Phase:

Participants will continue recording daily pelvic pain ratings via the Ethica App and engage in WHM via the WHM app for a further 8 weeks after the intervention phase.

In the final week of the follow-up phase, participants will undergo an eTVUS scan, blood sample collection to assess sympathetic nervous system function, hormone levels, and innate immune responses, and will complete the PPIQ and 3PSQ. These data will be used to evaluate long-term effects of the WHM intervention.

Study locations:

The site for eTVUS scanning will be Specialist Imaging Partners in North Adelaide. Blood samples, and completion of the PPIQ and 3PSQ, will also take place here during the baseline and follow-up phases.

All WHM workshops, supervised WHM sessions, and the mid- and end-intervention measurements (blood samples, PPIQ and 3PSQ) will take place at the Clinial Research Facility at the University of Adelaide Health and Medical Sciences Building (AHMS) situated on North Terrace, Adelaide CBD.
Intervention code [1] 328939 0
Treatment: Other
Comparator / control treatment
This trial employs a single-case experimental design (SCED) with randomised multiple baselines. Each of the 32 participants will serve as their own control, allowing for intensive study from baseline, intervention, and through to the follow-up period.

Study duration: The baseline phase will take from 1 to 6 weeks depending upon which group participants are randomised into and to help stagger the start time for small groups of 4 to 6 participants. The intervention phase will be 12 weeks, and the follow-up phase will be 8 weeks following completion of the intervention phase.
Control group
Active

Outcomes
Primary outcome [1] 338789 0
Pelvic pain
Timepoint [1] 338789 0
Participants to register daily pelvic pain scores for the study duration (baseline, intervention, and follow-up phases).
Primary outcome [2] 338790 0
Fatigue
Timepoint [2] 338790 0
Flinders Fatigue Scale completed once at baseline, mid-intervention (intervention week 6), end-intervention (intervention week 12) and follow-up (8 weeks post-intervention phase)
Primary outcome [3] 338791 0
Depression Anxiety and Stress
Timepoint [3] 338791 0
DASS21 questionnaire will be completed at baseline, mid-intervention (intervention week 6), end-intervention (intervention week 12) and follow-up (8 weeks post-intervention phase).
Secondary outcome [1] 437041 0
Endometriosis lesion size
Timepoint [1] 437041 0
Transvaginal ultrasound for endometriosis (eTVUS) will be carried out at three major time-points:

1. During the baseline phase, forming part of the participant inclusion/exclusion criteria (i.e., participants will be included if lesions are visible on scan).

2. Just prior to commencing the intervention phase (i.e., exposure to WHM training sessions).

3. At the end of the follow-up phase (i.e., 8 weeks post-intervention phase), to determine if the WHM has had an appreciable change on lesion characteristics.
Secondary outcome [2] 437042 0
Blood plasma levels of adrenaline, noradrenaline, adrenocorticotropic hormone (ACTH) and cortisol, assessed as a composite outcome by multiplex assay.
Timepoint [2] 437042 0
Single blood samples will be obtained at baseline, mid-intervention (intervention week 6), end-intervention (intervention week 12) and follow-up (8 weeks post-intervention phase).
Secondary outcome [3] 437471 0
Safety of the WHM for endometriosis
Timepoint [3] 437471 0
Participant safety will be monitored throughout the study at all time-points. During the WHM workshops, participants will have vital signs checked (core temperature, heart rate, blood oxygen saturation, blood pressure) and will be observed by trial staff (WHM trainer, study coordinators, and the trial nurse). Participants can contact the study coordinators via phone or email at any time when performing WHM at home to report adverse events and will be encouraged to seek medical attention if required.
Secondary outcome [4] 441850 0
Sleep Quality
Timepoint [4] 441850 0
Secondary outcome [5] 441851 0
Sleep Quality
Timepoint [5] 441851 0
B-PSQI questionnaire will be completed at baseline, mid-intervention (intervention week 6), end-intervention (intervention week 12) and follow-up (8 weeks post-intervention phase).

Eligibility
Key inclusion criteria
Diagnosis of endometriosis (according to European Society and Human Reproduction and Embryology (ESHRE) guidelines)
Endometriosis lesions visible on eTVUS scan
Aged 18 years or older
Rate average period pain over past two menstrual cycles as at least 3/10 on an 11-point numerical rating scale (NRS)
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Health conditions contraindicating participation in WHM training (e.g., coronary heart disease, cold urticaria etc.)
Are pregnant
Have had surgery in the past 6 months
Are intending to have surgery (e.g., laparoscopy for endometriosis) over the duration of the trial

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
Other
Other design features
This is an experimental study featuring a non-concurrent, variable multiple-baseline across subjects, based on menstrual cycle, followed by application of a single intervention (The Wim Hof Method). Based on consumer advisory input, this change was made prior to commencement of participant recruitment.
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Safety outcomes will be analysed descriptively, with the numbers, proportions, and descriptions of any adverse events reported.
Feasibility outcomes will be analysed descriptively (for quantitative outcomes) or through content analysis (for qualitative data).
Efficacy outcomes will be analysed descriptively and visually (for all data), in line with recommendations in the literature. Pain data will also be statistically analysed using a multivariate test statistic.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/12/2024
Actual
Date of last participant enrolment
Anticipated
28/02/2025
Actual
Date of last data collection
Anticipated
29/08/2025
Actual
Sample size
Target
32
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 316853 0
Charities/Societies/Foundations
Name [1] 316853 0
Wilson Foundation
Country [1] 316853 0
Australia
Primary sponsor type
University
Name
The University of Adelaide
Address
Country
Australia
Secondary sponsor category [1] 319097 0
None
Name [1] 319097 0
Address [1] 319097 0
Country [1] 319097 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 315613 0
Bellberry Human Research Ethics Committee L
Ethics committee address [1] 315613 0
Ethics committee country [1] 315613 0
Australia
Date submitted for ethics approval [1] 315613 0
15/08/2024
Approval date [1] 315613 0
04/11/2024
Ethics approval number [1] 315613 0
2024-09-1158

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

Contacts
Principal investigator
Name 135254 0
Prof Mark Hutchinson
Address 135254 0
The University of Adelaide, School of Medical Sciences, 30 Frome Road, Adelaide SA 5005.
Country 135254 0
Australia
Phone 135254 0
+61 8 8313 0322
Fax 135254 0
Email 135254 0
mark.hutchinson@adelaide.edu.au
Contact person for public queries
Name 135255 0
Dr Kelsi Dodds
Address 135255 0
The University of Adelaide, School of Medical Sciences, 30 Frome Road, Adelaide SA 5005.
Country 135255 0
Australia
Phone 135255 0
+61 8 8313 7198
Fax 135255 0
Email 135255 0
kelsi.dodds@adelaide.edu.au
Contact person for scientific queries
Name 135256 0
Mr Joshua Woenig
Address 135256 0
The University of Adelaide, School of Medical Sciences, 30 Frome Road, Adelaide SA 5005.
Country 135256 0
Australia
Phone 135256 0
+61 8 8313 4261
Fax 135256 0
Email 135256 0
josh.woenig@adelaide.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
Individual data will not be shared due to the nature of the data and to respect the privacy and confidentiality of all participants.


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.