Axial SpondyloarthritisNCT02744014
Add-on Therapy for Axial Spondyloarthritis
A study testing Add-on Therapy for Axial Spondyloarthritis in people with Axial Spondyloarthritis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.
Trial summary
Rationale: Recent investigations suggest that, through certain concentration/meditation techniques, it is possible to modulate autonomic activity. The results of a recent randomized controlled trial investigating the "Wim Hof Method" have shown a direct biological effect on in-vivo cytokine production and are strongly… Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Axial Spondyloarthritis
- What is being tested?
- Add-on Therapy for Axial Spondyloarthritis
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 2 sitesNetherlands
- Study dates
- 21 Apr 2016to 19 Dec 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Clinical diagnosis of axSpA as assessed by the treating rheumatologist fulfilling the ASAS classification for axial SpA [Rudwaleit 2009]
- Between 18 and 45 years of age at screening
- Active disease as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of >2.1 and a CRP value of ≥5 at the screening visit.
- Ability and willingness to participate to the study and give written informed consent.
Who cannot join
- Patients who cannot give written consent or, in the opinion of the investigator, cannot comply to the requirements of the study protocol. Significant comorbidity, including a cardiac, renal, hepatic, neurological, metabolic or any other severe disease, which in the opinion of the investigator may interfere with the study or lead to deleterious effects for the patient.
- Recent history of (or persistent) infection requiring hospitalization or antibiotic treatment within 4 weeks of baseline.
- If female, patient should not be pregnant. A urine pregnancy-test will be performed at screening and has to be negative.
- Initiation of treatment with corticosteroids or DMARDs (synthetic and biologic) within 8 weeks before screening.
- Initiation of treatment with NSAID within 2 weeks before screening.
- Variation of the treatment doses within 6 weeks of screening.
Show all 10Show fewer
- Intra-articular injection with corticosteroids within 4 weeks prior to screening.
- Daily doses of systemic corticosteroids exceeding the equivalent of 10 mg prednisolone per day.
- Use of other drugs and treatments that may affect the evaluation of systemic inflammation as judged by the investigator.
- Cardiovascular risk factors such as a personal history of cardiovascular disease, familial history of major adverse cardiovascular events (MACE) at age younger than 45 yrs, hypercholesterolemia and stroke.
Trial locations and contacts
2 sites in 1 country.
Netherlands2 sites
Academic Medical Center
Amsterdam
Ziekenhuis Bernhoven
Uden
About this study
Official title: Evidence-Based Mindset & Physical Therapy for Add-on Treatment of Active Axial Spondyloarthritis: Safety and Efficacy
Rationale: Recent investigations suggest that, through certain concentration/meditation techniques, it is possible to modulate autonomic activity. The results of a recent randomized controlled trial investigating the "Wim Hof Method" have shown a direct biological effect on in-vivo cytokine production and are strongly encouraging the clinical evaluation of the technique's efficacy in immune-mediated inflammatory diseases.
Objective: To investigate whether an add-on mindset \& physical therapy program based on the "Wim Hof Method" can safely and efficaciously be applied in patients with active axial spondyloarthritis.
Read more
Study design: Prospective open-label randomized controlled trial, safety and efficacy.
Study population: Twenty-four patients with active axial spondyloarthritis between 18 and 45 years of age.
Intervention: A 30-day training program of add-on mindset and physical therapy for axial spondyloarthritis, using the methodology as designed and instructed by Wim Hof. It involves breathing techniques, training of mindset and concentration, and gradual cold exposure.
Main study parameters/endpoints: Safety evaluation of the program is the primary aim of the study. Secondary endpoint is the modulation of serum CRP levels. Exploratory objectives include modulation of clinical disease activity (ASDAS), quality of life (SF-36, EQ-5D), depressive symptoms (HADS), and predictive role of generalized and specific outcome expectancies (EPQ-N, LOT-R, VAS scales).
Read the detailed description
Axial spondyloarthritis (axSpA) is a common systemic autoinflammatory disease affecting approximately 7 in 1.000 individuals. Recent investigations suggest that, through certain concentration/meditation techniques, it is possible to modulate autonomic activity. The endotoxemia experiment in an individual (named Wim Hof) who used a self-created concentration/meditation technique is strongly supportive of these findings. The use of his technique - including breathing techniques, training of mindset and concentration, and gradual cold exposure - seemed to evoke a controlled stress response. This response was characterized by sympathetic nervous system activation and subsequent catecholamine/cortisol release, which seemed to attenuate the innate immune response. The remarkable results in the studied individual led to a randomised controlled trial of this technique at the Radboud UMC. Twenty-four healthy individuals were randomised to receive an instruction course of the technique or no instructions at all and subsequently underwent an endotoxemia experiment. The experiment involved the intravenous administration of very low doses of lipopolysaccharide and measuring the in-vivo cytokine response and clinical symptoms. The results of this study have shown a direct biological effect on in-vivo cytokine production and are strongly encouraging the evaluation of the technique's efficacy in clinical practice.
The techniques of the Wim Hof Method have been modulated to a scientifically reproducible mindset \& physical training program for add-on therapy of axSpA. Specifically, it has been adjusted for potential functional limitations of axSpA.
Primary Objective: To investigate whether the add-on mindset \& physical therapy program can safely be applied in patients with active axSpA using clinical safety parameters.
Secondary Objective: To assess whether the add-on mindset \& physical therapy program can modulate objective signs of inflammation in patients with active axSpA using serum biomarkers (e.g. CRP).
Exploratory objective: To assess whether the add-on mindset \& physical therapy program has an influence on the Ankylosing Spondylitis Disease Activity Score, quality of life, and depressive symptoms (HADS), and to explore the predictive role of generalized and specific outcome expectancies in patients with active axSpA
- Conditions
- Axial Spondyloarthritis
- Being tested
- Add-on Therapy for Axial Spondyloarthritis
- Medical subject headings
- Axial Spondyloarthritis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Add-on Therapy for Axial SpondyloarthritisBehavioural
Also called Wim Hof Method
| Study group | Role | What they receive |
|---|---|---|
| Early intervention group | Experimental | The program starts with a 30-days training course led by course instructor Wim Hof and supervised by the research team. The mindset \& physical therapy based on the Wim Hof Method includes breathing techniques, training of mindset and concentration, and gradual cold exposure. Receives: Behavioral: Add-on Therapy for Axial Spondyloarthritis |
| Late intervention group | Other | This group will receive the same training with a delay of 60-90 days, serving initially as control. Receives: Behavioral: Add-on Therapy for Axial Spondyloarthritis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Measured: 60 days
Change in CRP value
Measured: 60 days
Secondary outcomes (2)
Change in circulating cytokines
Measured: 30, 60, 180 days
Change in other serum inflammation biomarkers (ESR, calprotectin)
Measured: 30, 60, 180 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2016 (estimated)
- Study start21 Apr 2016
- Primary completion22 Mar 2017
- Study completion19 Dec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Axial SpondyloarthritisStudies of the same condition, open and under way.
- More trials run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- Bernhoven Hospital, Radboud University Medical Center
- Responsible party
- Principal investigator, D.L.P. Baeten, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
- Investigators
- Dominique Baeten, MD PhD, Principal investigator, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02744014
- Sponsor's protocol ID
- Academic_Medical_Center
- Status last verified
- Jun 2018
- First submitted
- 2 Mar 2016
- Last updated
- 12 Jun 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Kox M, Stoffels M, Smeekens SP, van Alfen N, Gomes M, Eijsvogels TM, Hopman MT, van der Hoeven JG, Netea MG, Pickkers P. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012 Jun;74(5):489-94. doi: 10.1097/PSY.0b013e3182583c6d.
PubMed 22685240Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7379-84. doi: 10.1073/pnas.1322174111. Epub 2014 May 5.
PubMed 24799686Buijze GA, De Jong HMY, Kox M, van de Sande MG, Van Schaardenburg D, Van Vugt RM, Popa CD, Pickkers P, Baeten DLP. An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial. PLoS One. 2019 Dec 2;14(12):e0225749. doi: 10.1371/journal.pone.0225749. eCollection 2019.
PubMed 31790484
Study at a glance
From the registry record, last updated by the sponsor on 12 Jun 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Evidence-Based Mindset & Physical Therapy for Add-on Treatment of Active Axial Spondyloarthritis: Safety and Efficacy
- ClinicalTrials.gov ID
- NCT02744014
- Acronym / sponsor ID
- Academic_Medical_Center
- Conditions
- Axial Spondyloarthritis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)University, hospital or other
- Collaborators
- Bernhoven Hospital, Radboud University Medical Center
- Study start
- 21 Apr 2016 (actual)
- Primary completion
- 22 Mar 2017 (actual)
- Study completion
- 19 Dec 2017 (actual)
- First posted
- 19 Apr 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Rationale: Recent investigations suggest that, through certain concentration/meditation techniques, it is possible to modulate autonomic activity. The results of a recent randomized controlled trial investigating the "Wim Hof Method" have shown a direct biological effect on in-vivo cytokine production and are strongly encouraging the clinical evaluation of the technique's efficacy in immune-mediated inflammatory diseases.
Objective: To investigate whether an add-on mindset \& physical therapy program based on the "Wim Hof Method" can safely and efficaciously be applied in patients with active axial spondyloarthritis.
Study design: Prospective open-label randomized controlled trial, safety and efficacy.
Study population: Twenty-four patients with active axial spondyloarthritis between 18 and 45 years of age.
Intervention: A 30-day training program of add-on mindset and physical therapy for axial spondyloarthritis, using the methodology as designed and instructed by Wim Hof. It involves breathing techniques, training of mindset and concentration, and gradual cold exposure.
Main study parameters/endpoints: Safety evaluation of the program is the primary aim of the study. Secondary endpoint is the modulation of serum CRP levels. Exploratory objectives include modulation of clinical disease activity (ASDAS), quality of life (SF-36, EQ-5D), depressive symptoms (HADS), and predictive role of generalized and specific outcome expectancies (EPQ-N, LOT-R, VAS scales).
Detailed description
Axial spondyloarthritis (axSpA) is a common systemic autoinflammatory disease affecting approximately 7 in 1.000 individuals. Recent investigations suggest that, through certain concentration/meditation techniques, it is possible to modulate autonomic activity. The endotoxemia experiment in an individual (named Wim Hof) who used a self-created concentration/meditation technique is strongly supportive of these findings. The use of his technique - including breathing techniques, training of mindset and concentration, and gradual cold exposure - seemed to evoke a controlled stress response. This response was characterized by sympathetic nervous system activation and subsequent catecholamine/cortisol release, which seemed to attenuate the innate immune response. The remarkable results in the studied individual led to a randomised controlled trial of this technique at the Radboud UMC. Twenty-four healthy individuals were randomised to receive an instruction course of the technique or no instructions at all and subsequently underwent an endotoxemia experiment. The experiment involved the intravenous administration of very low doses of lipopolysaccharide and measuring the in-vivo cytokine response and clinical symptoms. The results of this study have shown a direct biological effect on in-vivo cytokine production and are strongly encouraging the evaluation of the technique's efficacy in clinical practice.
The techniques of the Wim Hof Method have been modulated to a scientifically reproducible mindset \& physical training program for add-on therapy of axSpA. Specifically, it has been adjusted for potential functional limitations of axSpA.
Primary Objective: To investigate whether the add-on mindset \& physical therapy program can safely be applied in patients with active axSpA using clinical safety parameters.
Secondary Objective: To assess whether the add-on mindset \& physical therapy program can modulate objective signs of inflammation in patients with active axSpA using serum biomarkers (e.g. CRP).
Exploratory objective: To assess whether the add-on mindset \& physical therapy program has an influence on the Ankylosing Spondylitis Disease Activity Score, quality of life, and depressive symptoms (HADS), and to explore the predictive role of generalized and specific outcome expectancies in patients with active axSpA
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Early intervention group | Experimental | Behavioral: Add-on Therapy for Axial SpondyloarthritisThe program starts with a 30-days training course led by course instructor Wim Hof and supervised by the research team. The mindset \& physical therapy based on the Wim Hof Method includes breathing techniques, training of mindset and concentration, and gradual cold exposure. |
| Late intervention group | Other | Behavioral: Add-on Therapy for Axial SpondyloarthritisThis group will receive the same training with a delay of 60-90 days, serving initially as control. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- Clinical diagnosis of axSpA as assessed by the treating rheumatologist fulfilling the ASAS classification for axial SpA [Rudwaleit 2009]
- Between 18 and 45 years of age at screening
- Active disease as defined by an Ankylosing Spondylitis Disease Activity Score (ASDAS) of >2.1 and a CRP value of ≥5 at the screening visit.
- Ability and willingness to participate to the study and give written informed consent.
Key exclusion criteria (10 listed)
- Patients who cannot give written consent or, in the opinion of the investigator, cannot comply to the requirements of the study protocol. Significant comorbidity, including a cardiac, renal, hepatic, neurological, metabolic or any other severe disease, which in the opinion of the investigator may interfere with the study or lead to deleterious effects for the patient.
- Recent history of (or persistent) infection requiring hospitalization or antibiotic treatment within 4 weeks of baseline.
- If female, patient should not be pregnant. A urine pregnancy-test will be performed at screening and has to be negative.
- Initiation of treatment with corticosteroids or DMARDs (synthetic and biologic) within 8 weeks before screening.
- Initiation of treatment with NSAID within 2 weeks before screening.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Add-on Therapy for Axial SpondyloarthritisAlso: Wim Hof Method | Behavioural | Early intervention group, Late intervention group |
Primary outcome
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time frame: 60 days
Number of Participants With Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment
Change in CRP value
Time frame: 60 days
2 secondary outcomes
Change in circulating cytokines
Time frame: 30, 60, 180 days
Change in other serum inflammation biomarkers (ESR, calprotectin)
Time frame: 30, 60, 180 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Jun 2018.
- Background: PubMed 22685240Kox M, Stoffels M, Smeekens SP, van Alfen N, Gomes M, Eijsvogels TM, Hopman MT, van der Hoeven JG, Netea MG, Pickkers P. The influence of concentration/meditation on autonomic nervous system activity and the innate immune response: a case study. Psychosom Med. 2012 Jun;74(5):489-94. doi: 10.1097/PSY.0b013e3182583c6d.
- Results publication: PubMed 24799686Kox M, van Eijk LT, Zwaag J, van den Wildenberg J, Sweep FC, van der Hoeven JG, Pickkers P. Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans. Proc Natl Acad Sci U S A. 2014 May 20;111(20):7379-84. doi: 10.1073/pnas.1322174111. Epub 2014 May 5.
- Derived from this study: PubMed 31790484Buijze GA, De Jong HMY, Kox M, van de Sande MG, Van Schaardenburg D, Van Vugt RM, Popa CD, Pickkers P, Baeten DLP. An add-on training program involving breathing exercises, cold exposure, and meditation attenuates inflammation and disease activity in axial spondyloarthritis - A proof of concept trial. PLoS One. 2019 Dec 2;14(12):e0225749. doi: 10.1371/journal.pone.0225749. eCollection 2019.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dominique Baeten, MD PhD principal investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Add-on Therapy for Axial Spondyloarthritis in people with Axial Spondyloarthritis, run by Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) at 2 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 60 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02744014, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jun 2018.