Exposure Therapy vs. Standardized Education for Distress Related to Somatic Symptoms (SOMEX1)

Randomized Controlled Trial of Internet-delivered Exposure-based Treatment vs. Standardized Education for Distress Related to Somatic Symptoms in Primary Care

The annual societal cost of medically unexplained symptoms in Sweden is approximately 40 billion SEK, i.e., similar to the annual cost of cancer. Prevalent chronic diseases like asthma and diabetes are also commonly associated with somatic symptoms that lead to significant distress and pervasive behavioral changes that result in functional impairment and place added strain on the health care system. Exposure-based treatment, where the patient willingly engages with stimuli that give rise to unwanted physical sensations or distress, has shown promise in reducing somatic symptom load and increasing quality of life in several conditions where patients commonly report substantial distress related to somatic symptoms, such as in asthma, musculoskeletal pain, and functional gastrointestinal syndromes. In routine care, however, access to such exposure-based treatment is limited. One reason for this is probably that there exists no flexible exposure-based treatment protocol that can be easily tailored to suit a wide spectrum of patient groups who suffer from distress related to recurrent somatic symptoms. In a recent single group feasibility trial (N=33) at Karolinska Institutet, Sweden, the investigators found that such a tailored exposure-based treatment delivered in an online text-based format can be acceptable, with high treatment adherence, adequate treatment satisfaction, large and lasting within-group improvement, and no serious adverse events. This is a randomized controlled trial (N=160) where the investigators aim to test if the same tailored internet-delivered exposure-based treatment is more efficacious than a standardized education control for adult patients with clinically significant distress related to somatic symptoms in a primary care setting. Primary outcome is change in self-rated somatic symptom burden as modelled using linear mixed models fitted on weekly Patient Health Questionnaire 15 sum scores over the treatment period. Long-term efficacy is assessed up to one year after treatment and cost-effectiveness is investigated based on the incremental cost-effectiveness ratio.

Study Overview

• Status: Active, not recruiting
• Conditions: Medically Unexplained Symptoms; Somatic Symptom and Related Disorders; Psychological Factors Affecting Other Medical Conditions
• Intervention / Treatment: Behavioral: Exposure; Behavioral: Standardized education; Behavioral: Prolonged assessment

Detailed Description

Approximately one fifth of primary care patients seek care for symptoms that cannot readily be given a medical explanation. In addition, primary care is tasked with offering care for prevalent chronic diseases such as asthma and diabetes where somatic symptoms often lead to distress and pervasive behavioral changes. Though a concern with somatic symptoms can be fully warranted, helpful, and transient, it can also be persistent and lead to much unnecessary suffering. Existing treatments commonly yield insufficient effects on medically unexplained symptoms.

Psychological factors - in particular the preoccupation with symptoms - have been found to affect the perception and intensity of a large number of physical symptoms, both with and without a clear medical genesis. In pain, it has for example been found that fear and the preoccupation with symptoms can have a more substantial predictive value for chronicity than pain itself. In general, in individuals who suffer from clinically significant symptom preoccupation, behaviors intended to evaluate symptoms, seek information about symptoms, or avoid discomfort have been found to often contribute to worsened function and increased symptom burden in the long term.

This makes exposure, where the patient willingly and systematically approaches stimuli that give rise to unwanted symptoms or discomfort while refraining from acting on symptoms, a logical intervention. There are several examples where exposure-based treatment has been found to be efficacious when protocols were written to suit a particular group of patients where distress associated with somatic symptoms is common, e.g., a particular functional somatic syndrome in terms of fibromyalgia and irritable bowel syndrome, or a chronic somatic condition such as asthma or atrial fibrillation. Typically, effects on symptoms and the preoccupation with symptoms have been large, and there is evidence to suggests that a reduction in somatic symptom burden may have been mediated by a reduction in symptom preoccupation or behaviors that serve to reduce distress in the short term.

Generalist primary care clinics typically do not have the resources necessary for administering specific psychological treatments for a large number specific functional somatic syndromes or chronic somatic conditions. The investigators suspect that a more general treatment protocol that can be tailored to suit a wide spectrum of physical symptoms could dramatically improve access to exposure-based treatment for patients with distress related to somatic symptoms. This may be particularly true if treatment can be delivered via the internet, which requires less therapist time but often results in similar effects as face-to-face treatment.

The investigators recently completed a feasibility trial at Karolinska Institutet, Sweden (NCT04511286), where the investigators found that an internet-delivered flexible exposure-based treatment for individuals with high levels of symptom preoccupation regardless of somatic symptom domain (N=33; e.g., functional gastrointestinal symptoms, atrial fibrillation, migraine) can be delivered with high treatment adherence, adequate client satisfaction, large and lasting improvement in self-reported somatic symptoms and symptom preoccupation, and no serious adverse events. It is thus motivated to evaluate this treatment format further.

In further evaluating the flexible exposure-based treatment approach for patients with distress related to somatic symptoms it is imperative to conduct a randomized controlled trial versus an informative control condition, focusing on effects on somatic symptoms and symptom preoccupation. It is also important to evaluate if the treatment can be effective in a routine clinical setting and when patients are referred via a clinician such as a general practitioner. In this trial, the investigators aim to evaluate if flexible internet-delivered exposure-based treatment is more effective than an internet-delivered standardized routine care education program for patients with distress related to somatic symptoms in primary care.

• Primary research question:

Compared to the control condition, does flexible internet-delivered exposure-based treatment lead to a larger average improvement in self-rated somatic symptom burden as assessed using the Patient Health Questionnaire 15 (PHQ-15)? Hypothesis: Yes.

• Key secondary research questions:

Compared to the control condition, does flexible internet-delivered exposure-based treatment lead to a larger average improvement in symptom preoccupation, psychiatric symptom burden, and functional impairment? Hypothesis: Yes.

In flexible internet-delivered exposure-based treatment, are effects typically maintained up to 12 months after treatment? Hypothesis: Yes.

Is flexible internet-delivered exposure-based treatment cost-effective compared to the control condition? Hypothesis: Yes.

Is the controlled effect of the flexible exposure-based treatment on self-rated somatic symptoms moderated by baseline symptoms and preoccupation? Hypothesis: Yes.

Is the effect of the flexible exposure-based treatment on self-rated somatic symptom burden mediated by a reduction in symptom preoccupation? Hypothesis: Yes.

• Study Type: Interventional
• Enrollment (Actual): 161
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Erland Axelsson, PhD; Phone Number: +46 0706171039; Email: erland.axelsson@ki.se

Study Locations

• Sweden
  • Stockholm, Sweden, 11763
    • Liljeholmen academic primary care clinic

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• (i) Either much bothered by at least one somatic symptom (2 points on at least one item of the PHQ-15) or at least a moderate overall somatic symptom burden (PHQ-15 sum ≥10), with (ii) recurrent distress related to somatic symptoms ≥4 months
• Interested in completing an intense psychological treatment with the aim of reducing distress associated with physical symptoms
• Adult (≥18 years old)
• Living in Stockholm County
• Can read and write in Swedish
• Complete baseline assessment

Exclusion Criteria:

• Symptoms best explained by, or clinical picture dominated by, severe health anxiety or a non-somatoform psychiatric disorder such as depression, panic disorder, primary insomnia, a chronic stress disorder, or an acute stress disorder
• Severe psychiatric condition or suicidal ideation
• Clear medical risk in taking part in exposure-based treatment (e.g., pregnancy) or somatic condition (e.g., recent cancer diagnosis), or treatment for somatic condition (e.g., recent chemotherapy), makes treatment unfeasible
• Continuous psychotropic medication (antidepressants, anticonvulsants, mood-stabilizers, antipsychotics) not stable in past 4 weeks, or not expected to remain stable over the main phase of the trial
• Severe alcohol or substance use disorder likely to interfere with treatment
• Planned absence for more than 1 week during the intended main phase

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Internet-delivered exposure-based treatment; 10 weeks of therapist-guided exposure-based treatment delivered via the Internet.	Behavioral: Exposure; Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Active Comparator: Internet-delivered standardized education and prolonged assessment; 10 weeks of therapist-guided intervention based on prolonged assessment and routine care educational material delivered via the Internet.	Behavioral: Standardized education; Standardized routine care education for individuals suffering from distress related to somatic symptoms, primarily focusing on healthy lifestyle behaviors such as sleep, diet, and exercise; Behavioral: Prolonged assessment; Patients are encouraged to keep a rudimentary symptom diary to track if and how their symptoms interact with mood and lifestyle behaviors

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patient Health Questionnaire-15 (PHQ-15)	Theoretical range: 0-30. A higher score indicates a higher subjective somatic symptom burden.	Change over the main phase, as modelled using data from all 11 assessments from the baseline assessment to the primary endpoint (≤45 days after treatment). Secondary analyses incorporate 6- and 12-months follow-up assessments.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Somatic Symptom Disorder-B Criteria Scale (SSD-12)	Theoretical range: 0-48. A higher score indicates higher degree of preoccupation with symptoms.	Change over the main phase, as modelled using data from all 11 assessments from the baseline assessment to the primary endpoint (≤45 days after treatment). Additional analyses incorporate 6- and 12-months follow-up assessments.
Symptom Preoccupation Scale (preliminary scale)	Under development. A higher score indicates higher degree of preoccupation with symptoms.	Change over the main phase, as modelled using data from all 11 assessments from the baseline assessment to the primary endpoint (≤45 days after treatment). Additional analyses incorporate 6- and 12-months follow-up assessments.
GAD-7	Theoretical range: 0-21. A higher score indicates more general anxiety.	Change over the main phase, as modelled using data from the baseline assessment and primary endpoint (≤45 days after treatment). Additional analyses incorporate 6- and 12-months follow-up assessments.
Patient Health Questionnaire (PHQ-9)	Theoretical range: 0-27. A higher score indicates more symptoms of depression.	Change over the main phase, as modelled using data from the baseline assessment and primary endpoint (≤45 days after treatment). Additional analyses incorporate 6- and 12-months follow-up assessments.
12-item WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)	Theoretical range: 0-100. A higher score indicates more disability.	Change over the main phase, as modelled using data from the baseline assessment and primary endpoint (≤45 days after treatment). Additional analyses incorporate 6- and 12-months follow-up assessments.
14-item Health Anxiety Inventory (HAI-14)	Theoretical range: 0-42. A higher score indicates more health anxiety.	Screening only
Alcohol Use Disorders Identification Test (AUDIT)	Theoretical range: 0-40. A higher score indicates more problematic alcohol use.	Screening only
Drug Use Disorders Identification Test (DUDIT)	Theoretical range: 0-44. A higher score indicates more problematic substance use.	Screening only
Credibility/Expectancy scale (C/E scale)	Theoretical range: 0-50. A higher score indicates higher credibility/expectancy.	Week 3 of main phase
Working Alliance Inventory (WAI)	Theoretical range: 6-42. A higher score indicates better relationship with the therapist.	Week 3 of main phase
Client Satisfaction Questionnaire (CSQ-8)	Theoretical range: 8-32. A higher score indicates higher satisfaction with treatment.	Primary endpoint assessment (≤45 days after treatment)
EuroQol 5D (EQ-5D)	Theoretical range: 0-1, i.e., scored as utility for the purpose of calculating quality-adjusted life years for health economic analysis. A higher utility score indicates a higher health-related quality of life.	Data from the baseline assessment, the primary endpoint, and the 6- and 12-month follow-up are used for health economic analysis focusing on the main phase.
Trimbos Institute and Institute of Medical Technology Questionnaire for Costs Associated with Psychiatric Illness (TIC-P)	This instrument is scored in terms of resource use for the purpose of calculating societal costs for health economic analysis.	Data from the baseline assessment, the primary endpoint, and the 6- and 12-month follow-up are used for health economic analysis focusing on the main phase.
Four questions corresponding to presumed components of subjective somatic symptom burden	These questions concern (1) somatic symptom severity, (2) somatic symptom frequency/duration, (3) distress related to somatic symptoms, and (4) the impact of somatic symptoms on disability. Answers are given on visual analogue scales.	Measured at screening, baseline assessment, and the primary endpoint
Seven questions probing into basic emotions related to somatic symptoms	Answers are given on visual analogue scales.	Measured at screening, baseline assessment, and the primary endpoint

Collaborators and Investigators

• Sponsor: Region Stockholm
• Collaborators: Karolinska Institutet
• Investigators: Principal Investigator: Erland Axelsson, PhD, Liljeholmen academic primary care clinic, Region Stockholm

Publications and helpful links

Helpful Links

• Simple exposure protocol administered over 10 weeks

Study record dates

Study Major Dates

• Study Start (Actual): October 7, 2021
• Primary Completion (Estimated): January 31, 2025
• Study Completion (Estimated): January 31, 2025

Study Registration Dates

• First Submitted: June 17, 2021
• First Submitted That Met QC Criteria: June 18, 2021
• First Posted (Actual): June 28, 2021

Study Record Updates

• Last Update Posted (Actual): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: primary care; exposure
• Additional Relevant MeSH Terms: Medically Unexplained Symptoms
• Other Study ID Numbers: 2021-01400

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: We are willing to consider reasonable requests for individual participant data (IPD) and to consult the responsible parties. However, we do not expect to be granted permission to share IPD as long as, under Swedish and European Union (EU) data protection and privacy legislation, the IPD constitutes personal data meaning that it is possible to, using the existing study database, link the IPD to an identifiable living natural person. Ten years after the last publication, the information necessary for individuals to be identified will be deleted and documentation from the trial will be archived for long-term storage. We expect to include anonymized IPD in this archive. It is our understanding that, under EU law, IPD without the existence of information necessary for individuals to be identified does not constitute personal because the IPD can no longer be linked to a living natural person. Thus, 10 years after the last publication and onwards, we expect to be able to share IPD on request.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No