Functional DisordersNCT05212467
AIR-program and HUS Internet Therapy Compared to Treatment as Usual in Functional Disorders and Post Covid-19 Condition
A study testing AIR-program, HUS Internet therapy and Treatment as usual in people with Functional Disorders and Post Covid-19, run by Helsinki University Central Hospital at 2 sites in Finland.
Trial summary
This study will compare an Amygdala and insula retraining (AIR) program to an internet therapy developed at Helsinki University Hospital. The study will be a multi-center randomized controlled trial. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Functional Disorders, Post Covid-19
- What is being tested?
- AIR-program, HUS Internet therapy and Treatment as usual
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 360 participants
- Where
- 2 sitesFinland
- Study dates
- 31 Jan 2022to 31 Dec 2024
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- • The criteria of bodily stress syndrome, fibromyalgia, chronic fatigue syndrome, or long Covid fulfilled AND
- Diagnostic examinations have ruled out the potential somatic reasons for the symptoms AND
- Disabling symptoms have lasted at least 3 months AND
- Patient is willing to receive a psychoeducation or brain retraining intervention.
Who cannot join
- • Patients for whom participation could be overly demanding because of physical constraints (for example, patients who cannot write because of dystonia or bedridden patients)
- Patients with presence of severe psychiatric and severe somatic disorders, e.g. moderate or severe depression or newly onset cancer for which the study could be overly strenuous.
Trial locations and contacts
2 sites in 1 country.
Finland2 sites, 2 recruiting
- Recruiting
Clinic for Functional Disorders, HUS
Helsinki, 00029
Markku Sainio, MD, PhD, +358 40 569 3186, markku.sainio@hus.fi
- Recruiting
Clinic for Long Covid, HUS
Helsinki, 00029
Helena Liira, MD, PhD, +358 50 577 1351, helena.liira@hus.fi
About this study
Official title: Amygdala and Insula Retraining (AIR) Program and HUS Internet Therapy Compared to Treatment as Usual in Bodily Stress Syndrome, Fibromyalgia, Post Covid-19, and Chronic Fatigue Syndrome (ME/CFS)
This study will compare an Amygdala and insula retraining (AIR) program to an internet therapy developed at Helsinki University Hospital. The study will be a multi-center randomized controlled trial. Study units will be recruited from the Network for Functional Disorders that is hosted by the HUS Clinic for Functional Disorders and potentially later from international collaborators. The trial will clarify whether internet-based non-drug based therapies are helpful in overcoming the central sensitization and the functional disabilities caused by these disorders.
Read the detailed description
Functional disorders are a challenging group of conditions treated both in primary and secondary care. Recently, mounting evidence shows that central nervous system sensitization is one of the involved mechanisms, giving new treatment opportunities. There are self-management programs and internet therapies that aim at overcoming the central sensitization by creating new neural networks in the brain. This study aims to test whether an Amygdala and insula retraining (AIR) program compared to an internet therapy developed at HUS (Helsinki University Hospital) and treatment as usual (TAU) is effective in the treatment of functional disorders, fibromyalgia, long Covid, and chronic fatigue syndrome (ME/CFS).
The investigators will perform a multi-center randomized controlled trial in volunteering health units and with volunteering patients aiming at 360 patients altogether. The physicians in charge of the patients will be recruited from the Network for Functional Disorders launched by the novel clinic at HUS. The participating centers will receive an introduction in functional disorders, the underlying mechanisms, and treatment opportunities.
For functional disorders, this study applies the ICD-11 primary care code of Bodily stress syndromes (BSS), which covers fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, and other, both single system and multiorgan functional disorders. In addition, for patients with fibromyalgia, chronic fatigue symptoms, and Post Covid-19 condition, we will apply specific diagnostic criteria. Both primary and secondary care treatment units that manage these disorders can recruit patients.
The studied interventions are an Amygdala and insula retraining (AIR) program and an internet therapy developed at HUS, and patients receive usual care in addition to these interventions. The third study arm consists of treatment as usual for six months after which the patients receive the AIR program or the internet therapy if they so wish. When the participating physicians consider that a patient could benefit from a self-management program, they introduce the trial to the patient. The consenting patient fills in a baseline survey and is followed up at 3, 6, and 12 months with the help of the HUSeCRF (online surveys at the HUS electronic Case Report Form), or research nurse's interviews.
This study will give new insight into the opportunities of self-management programs in the treatment of bodily stress syndromes, fibromyalgia, Post Covid-19, and ME/CFS. The investigators will find out whether the training programs increase patients' functional ability and quality of life as measured on a scale from 0 to 10. These scales and functional ability as measured by WHODAS 2.0 serve as main outcome measures for this study. This trial is the first large-scale randomized trial that assesses these methods developed to overcome the central sensitization of brain. The results will have an impact on the management of these common and often debilitating conditions.
- Conditions
- Functional Disorders, Post Covid-19
- Being tested
- AIR-program, HUS Internet therapy, Treatment as usual
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AIR-programBehavioural
This is a guided self management program that is added on the treatment as usual.
HUS Internet therapyBehavioural
This is a guided self management program that is added on the treatment as usual.
Treatment as usualBehavioural
The patients receive routine care from their physician which may include drugs, visits or rehabilitation
| Study group | Role | What they receive |
|---|---|---|
| AIR-program | Active comparator | • The Amygdala and insula retraining program consists of novel brain retraining approaches focused on hypothetically interrupting and retraining the conditioned defensive hyper-stimulation of the sympathetic nervous system and aspects of the immune system by the amygdala and insula, to bring the brain and body back to homeostasis. It includes supportive techniques such as breathing, meditation, and neurolinguistic programming. The patients are invited to an online program of video session and eight weekly 2 h webinar sessions followed by three monthly sessions. The patients are assigned to do daily homework that takes approximately 15 to 20 min to complete Receives: Behavioral: AIR-program; Behavioral: Treatment as usual |
| HUS Internet therapy | Active comparator | The HUS internet therapy for bodily stress syndromes (iHUSbss) includes psychoeducation about autonomic nervous system and of the effects of patient's own thinking and action on the nervous system. The exercises aim at relaxing the body, at novel ways to observe the symptoms, and at developing acceptance and self-compassion. The program includes exercises that are done regularly in everyday life. Receives: Behavioral: HUS Internet therapy; Behavioral: Treatment as usual |
| Treatment as usual | Placebo comparator | The patients may have appointments with their physician, physiotherapist, or another health professional, and they may attend group interventions. If possible, medication is kept the same during the intervention and three months afterwards. If there is need to change the medication during the trial, the changes will be recorded. Appointments with health professionals and attendance in group interventions are monitored. Receives: Behavioral: Treatment as usual |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in functional ability as measured by the WHODAS2.0 instrument at six months.
Measured: 3, 6 and 12 months
Secondary outcomes (7)
Change from baseline in quality of life as measured by EUROHIS-8
Measured: 3, 6 and 12 months
Change from baseline in health related quality of life as measured by 15D
Measured: 3, 6 and 12 months
Change from baseline in symptoms as measured by SSD-12 and PHQ-15
Measured: 3, 6 and 12 months
Change from baseline in depression as measured by PHQ-9
Measured: 3, 6 and 12 months
Change from baseline in anxiety as measured by GAD-7
Measured: 3, 6 and 12 months
Change in sleep as measured by ISI
Measured: 3, 6 and 12 months
Change in resilience as measured by Resilience Scale-14
Measured: 3, 6 and 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jan 2022
- Study start31 Jan 2022 (estimated)
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Functional DisordersStudies of the same condition, open and under way.
- 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
- Parallel groups
- Model description
- Patients are randomized to one of the three treatment groups
- Masking
- Double blind
- Who is masked
- Investigator, Outcomes assessor
- Enrolment
- 360 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Helsinki University Central Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Helena Liira, Helsinki University Central Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05212467
- Sponsor's protocol ID
- HUS/2239/2021
- Status last verified
- Jan 2022
- First submitted
- 24 Jan 2022
- Last updated
- 10 Feb 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: We have applied for EU Horizon funding and may share data in that project.
Publications
Vangelova-Korpinen V, Liira H, Kurki SN, Sainio M, Malmivaara A, Kanerva M, Stenberg JH, Varonen M, Venalainen M, Vuorela P, Arokoski J. Effectiveness of mindfulness-based online therapy or internet-delivered cognitive behavioral therapy compared with treatment as usual among patients with persistent somatic symptoms: Protocol for a randomized controlled trial. PLoS One. 2025 Feb 12;20(2):e0316169. doi: 10.1371/journal.pone.0316169. eCollection 2025.
PubMed 39937805
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Amygdala and Insula Retraining (AIR) Program and HUS Internet Therapy Compared to Treatment as Usual in Bodily Stress Syndrome, Fibromyalgia, Post Covid-19, and Chronic Fatigue Syndrome (ME/CFS)
- ClinicalTrials.gov ID
- NCT05212467
- Acronym / sponsor ID
- HUS/2239/2021
- Conditions
- Functional Disorders, Post Covid-19
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 360 participants (estimated)
- Lead sponsor
- Helsinki University Central HospitalUniversity, hospital or other
- Study start
- 31 Jan 2022 (estimated)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 28 Jan 2022 (actual)
- 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.
This study will compare an Amygdala and insula retraining (AIR) program to an internet therapy developed at Helsinki University Hospital. The study will be a multi-center randomized controlled trial. Study units will be recruited from the Network for Functional Disorders that is hosted by the HUS Clinic for Functional Disorders and potentially later from international collaborators. The trial will clarify whether internet-based non-drug based therapies are helpful in overcoming the central sensitization and the functional disabilities caused by these disorders.
Detailed description
Functional disorders are a challenging group of conditions treated both in primary and secondary care. Recently, mounting evidence shows that central nervous system sensitization is one of the involved mechanisms, giving new treatment opportunities. There are self-management programs and internet therapies that aim at overcoming the central sensitization by creating new neural networks in the brain. This study aims to test whether an Amygdala and insula retraining (AIR) program compared to an internet therapy developed at HUS (Helsinki University Hospital) and treatment as usual (TAU) is effective in the treatment of functional disorders, fibromyalgia, long Covid, and chronic fatigue syndrome (ME/CFS).
The investigators will perform a multi-center randomized controlled trial in volunteering health units and with volunteering patients aiming at 360 patients altogether. The physicians in charge of the patients will be recruited from the Network for Functional Disorders launched by the novel clinic at HUS. The participating centers will receive an introduction in functional disorders, the underlying mechanisms, and treatment opportunities.
For functional disorders, this study applies the ICD-11 primary care code of Bodily stress syndromes (BSS), which covers fibromyalgia, irritable bowel syndrome, multiple chemical sensitivities, and other, both single system and multiorgan functional disorders. In addition, for patients with fibromyalgia, chronic fatigue symptoms, and Post Covid-19 condition, we will apply specific diagnostic criteria. Both primary and secondary care treatment units that manage these disorders can recruit patients.
The studied interventions are an Amygdala and insula retraining (AIR) program and an internet therapy developed at HUS, and patients receive usual care in addition to these interventions. The third study arm consists of treatment as usual for six months after which the patients receive the AIR program or the internet therapy if they so wish. When the participating physicians consider that a patient could benefit from a self-management program, they introduce the trial to the patient. The consenting patient fills in a baseline survey and is followed up at 3, 6, and 12 months with the help of the HUSeCRF (online surveys at the HUS electronic Case Report Form), or research nurse's interviews.
This study will give new insight into the opportunities of self-management programs in the treatment of bodily stress syndromes, fibromyalgia, Post Covid-19, and ME/CFS. The investigators will find out whether the training programs increase patients' functional ability and quality of life as measured on a scale from 0 to 10. These scales and functional ability as measured by WHODAS 2.0 serve as main outcome measures for this study. This trial is the first large-scale randomized trial that assesses these methods developed to overcome the central sensitization of brain. The results will have an impact on the management of these common and often debilitating conditions.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Patients are randomized to one of the three treatment groups
| Arm | Type | Receives |
|---|---|---|
| AIR-program | Active comparator | Behavioral: AIR-program, Behavioral: Treatment as usual• The Amygdala and insula retraining program consists of novel brain retraining approaches focused on hypothetically interrupting and retraining the conditioned defensive hyper-stimulation of the sympathetic nervous system and aspects of the immune system by the amygdala and insula, to bring the brain and body back to homeostasis. It includes supportive techniques such as breathing, meditation, and neurolinguistic programming. The patients are invited to an online program of video session and eight weekly 2 h webinar sessions followed by three monthly sessions. The patients are assigned to do daily homework that takes approximately 15 to 20 min to complete |
| HUS Internet therapy | Active comparator | Behavioral: HUS Internet therapy, Behavioral: Treatment as usualThe HUS internet therapy for bodily stress syndromes (iHUSbss) includes psychoeducation about autonomic nervous system and of the effects of patient's own thinking and action on the nervous system. The exercises aim at relaxing the body, at novel ways to observe the symptoms, and at developing acceptance and self-compassion. The program includes exercises that are done regularly in everyday life. |
| Treatment as usual | Placebo comparator | Behavioral: Treatment as usualThe patients may have appointments with their physician, physiotherapist, or another health professional, and they may attend group interventions. If possible, medication is kept the same during the intervention and three months afterwards. If there is need to change the medication during the trial, the changes will be recorded. Appointments with health professionals and attendance in group interventions are monitored. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- • The criteria of bodily stress syndrome, fibromyalgia, chronic fatigue syndrome, or long Covid fulfilled AND
Key exclusion criteria (2 listed)
- • Patients for whom participation could be overly demanding because of physical constraints (for example, patients who cannot write because of dystonia or bedridden patients)
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 |
|---|---|---|
| AIR-programThis is a guided self management program that is added on the treatment as usual. | Behavioural | AIR-program |
| HUS Internet therapyThis is a guided self management program that is added on the treatment as usual. | Behavioural | HUS Internet therapy |
| Treatment as usualThe patients receive routine care from their physician which may include drugs, visits or rehabilitation | Behavioural | AIR-program, HUS Internet therapy, Treatment as usual |
Primary outcome
Change from baseline in functional ability as measured by the WHODAS2.0 instrument at six months.
Time frame: 3, 6 and 12 months
7 secondary outcomes
Change from baseline in quality of life as measured by EUROHIS-8
Time frame: 3, 6 and 12 months
Change from baseline in health related quality of life as measured by 15D
Time frame: 3, 6 and 12 months
Change from baseline in symptoms as measured by SSD-12 and PHQ-15
Time frame: 3, 6 and 12 months
Change from baseline in depression as measured by PHQ-9
Time frame: 3, 6 and 12 months
Change from baseline in anxiety as measured by GAD-7
Time frame: 3, 6 and 12 months
Change in sleep as measured by ISI
Time frame: 3, 6 and 12 months
Change in resilience as measured by Resilience Scale-14
Time frame: 3, 6 and 12 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2022.
- Derived from this study: PubMed 39937805Vangelova-Korpinen V, Liira H, Kurki SN, Sainio M, Malmivaara A, Kanerva M, Stenberg JH, Varonen M, Venalainen M, Vuorela P, Arokoski J. Effectiveness of mindfulness-based online therapy or internet-delivered cognitive behavioral therapy compared with treatment as usual among patients with persistent somatic symptoms: Protocol for a randomized controlled trial. PLoS One. 2025 Feb 12;20(2):e0316169. doi: 10.1371/journal.pone.0316169. eCollection 2025.
- Individual participant dataSharing planned: Undecided. We have applied for EU Horizon funding and may share data in that project.
Related trials for Functional Disorders
Active, not recruiting
Measuring Impact of Computer Gaming on Arm Use in Rett Syndrome
Rett Syndrome
RecruitingPhase 3
Vibegron for ENergy Thinking and Resilience in Aging
Obesity
Not yet recruiting
Creatine and Beta-Hydroxy-Beta-Methylbutyrate (HMB) Supplementation Plus Home-Based Exercise for Sarcopenia in Huntington's Disease
Huntington Disease, Sarcopenia
Active, not recruiting
Smartphone-Guided Paced Breathing and Aerobic Exercise for Essential Hypertension
Essential (Primary) Hypertension
Recruiting
Effects of Mirror Therapy and Motor Imagery on Upper Limb Motor Functions in Middle Cerebral Artery Stroke
Stroke
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.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing AIR-program, HUS Internet therapy and Treatment as usual in people with Functional Disorders and Post Covid-19, run by Helsinki University Central Hospital at 2 sites in Finland.
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 2 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: status not confirmed, as of the sponsor's last update on 10 Feb 2022. 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 Finland. 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. Some participants in this study may receive a placebo. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Helena Liira, MD, PhD (+358 50 577 1351, helena.liira@hus.fi), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in functional ability as measured by the WHODAS2.0 instrument at six months. (time frame: 3, 6 and 12 months). 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 NCT05212467, which also lists 1 linked publication.
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 10 Feb 2022.