AIR-program and HUS Internet Therapy Compared to Treatment as Usual in Functional Disorders and Post Covid-19 Condition

• ClinicalTrials.gov Identifier: NCT05212467
• Recruitment Status: Recruiting
• First Posted: January 28, 2022
• Last Update Posted: February 10, 2022
• Sponsor: Helsinki University Central Hospital
• Information provided by (Responsible Party): Helena Liira, Helsinki University Central Hospital

Tracking Information

• First Submitted Date: January 24, 2022
• First Posted Date: January 28, 2022
• Last Update Posted Date: February 10, 2022
• Estimated Study Start Date: January 31, 2022
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: January 24, 2022): Change from baseline in functional ability as measured by the WHODAS2.0 instrument at six months. [ Time Frame: 3, 6 and 12 months ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: January 24, 2022)

• 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 ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: AIR-program and HUS Internet Therapy Compared to Treatment as Usual in Functional Disorders and Post Covid-19 Condition
• 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)
• Brief 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. 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 Type: Interventional
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

Patients are randomized to one of the three treatment groups

Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Treatment

Condition

• Functional Disorders
• Post Covid-19

Intervention

• Behavioral: AIR-program
  This is a guided self management program that is added on the treatment as usual.
• Behavioral: HUS Internet therapy
  This is a guided self management program that is added on the treatment as usual.
• Behavioral: Treatment as usual
  The patients receive routine care from their physician which may include drugs, visits or rehabilitation

Study Arms

• Active Comparator: AIR-program
  • 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
  Interventions:

  • Behavioral: AIR-program
  • Behavioral: Treatment as usual
• Active Comparator: HUS Internet therapy
  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.
  Interventions:

  • Behavioral: HUS Internet therapy
  • Behavioral: Treatment as usual
• Placebo Comparator: Treatment as usual
  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.
  Intervention: Behavioral: Treatment as usual

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: January 24, 2022): 360
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 31, 2024
• Estimated Primary Completion Date: December 31, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• • 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.

Exclusion Criteria:

• • 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Helena Liira, MD, PhD; +358 50 577 1351; helena.liira@hus.fi

Contact: Jari Arokoski, Prof; +358 50 428 7901; jari.arokoski@hus.fi

• Listed Location Countries: Finland

Administrative Information

• NCT Number: NCT05212467
• Other Study ID Numbers: HUS/2239/2021
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided
• Plan Description: We have applied for EU Horizon funding and may share data in that project.

• Current Responsible Party: Helena Liira, Helsinki University Central Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Helsinki University Central Hospital
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Helsinki University Central Hospital
• Verification Date: January 2022