Trial Outcomes & Findings for Exposure-Based Treatment for Undifferentiated Somatic Symptom Disorder (NCT NCT04511286)

NCT ID: NCT04511286

Last Updated: 2025-03-19

Results Overview

According to the Patient Health Questionnaire-15 (PHQ-15, theoretical range: 0-30, higher score indicates more distressing physical symptoms)

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 33 participants
• Primary outcome timeframe: Pre-treatment assessment (within 2 weeks before treatment)
• Results posted on: 2025-03-19

Participant Flow

We originally aimed to recruit 40 participants for 80% power in two-sided tests of moderate effects (d=0.5) on efficacy outcomes measured at two time points, given a 5% alpha and 15% missing data at post-treatment. In light of the high data retention, prior to the data analysis, we ended the recruitment with 33 participants included in November 2020.

All participants were enrolled in treatment.

Participant milestones

Measure	Internet-delivered Exposure-based Treatment Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Overall Study STARTED	33
Overall Study COMPLETED	32
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Age, Continuous	46 years STANDARD_DEVIATION 14 • n=33 Participants
Sex: Female, Male Female	22 Participants n=33 Participants
Sex: Female, Male Male	11 Participants n=33 Participants
Region of Enrollment Sweden	33 participants n=33 Participants
University education	27 Participants n=33 Participants
Employment Working full-time	21 Participants n=33 Participants
Employment Working part-time (<90%)	7 Participants n=33 Participants
Employment Retired	4 Participants n=33 Participants
Employment Student	1 Participants n=33 Participants

PRIMARY outcome

Timeframe: Pre-treatment assessment (within 2 weeks before treatment)

According to the Patient Health Questionnaire-15 (PHQ-15, theoretical range: 0-30, higher score indicates more distressing physical symptoms)

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 1: Distribution of Physical Symptoms	11.8 score on a scale Interval 3.0 to 20.0

PRIMARY outcome

Timeframe: Week 3 of treatment

Population: All participants completed the week 3 assessment.

Theoretical range: 0-50, higher score indicates higher credibility/expectancy

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 2: Credibility/Expectancy Based on the Credibility/Expectancy Scale	34.5 score on a scale Standard Deviation 7.0

PRIMARY outcome

Timeframe: Adherence data collected over the entire course of the treatment, up to 8 weeks.

Population: In this study, all 33 participants were enrolled in the same type of treatment and were thus offered to work with the same five treatment modules.

Preregistered target: at least 60% completed modules in the sample as a whole. In this study, all participants were enrolled in the same type of treatment and were thus offered to work with the same treatment modules. This outcome was the proportion of modules completed in total by all participants, out of the total modules available to all participants.

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=165 Modules Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 3: Adherence to the Protocol #1: Percentage Completed Modules in the Sample as a Whole	150 Modules

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

From 0 ("not at all relevant") to 10 ("extremely relevant"). Was originally intended to be administered at week 3, but was administered post-treatment due to an administrative error

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 4: Patient-reported Adequacy of Rationale as Assessed Using a Questionnaire Developed Specifically for This Purpose (Theoretical Range: 0-10)	8.4 score on a scale Standard Deviation 1.5

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

Population: Because the question about the measurement strategy was administered at the post-treatment assessment, which was completed by 32/33 participants, 32 was the denominator for this outcome.

Preregistered target: less than 30% missing data at post-treatment, and at least 75% finding the measurement strategy acceptable (less than 7 on a scale from 0 ["Not at all stressful/bothering"] to 10 ["Extremely stressful/bothering"])

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 5: Adequacy of the Measurement Strategy Missing data at post-treatment	1 Participants
Feasibility 5: Adequacy of the Measurement Strategy Found the measurement strategy acceptable (no cause for distress)	27 Participants

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

Theoretical range: 8-32, higher score indicates higher satisfaction. This sum score is based on 8 items, each scored 1-4.

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=32 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 6: Satisfaction With Treatment as Indicated by a Mean Client Satisfaction Questionnaire (CSQ-8) Score of at Least 22	25.3 score on a scale Standard Deviation 4.7

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

The respondent was instructed to describe up to three adverse events.

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=32 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 7a: Adverse Events Measured Using Free-text Items #1: Total Number of Reported Events	6 adverse events

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

Theoretical range: 0-80, higher score indicates more severe adverse events

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=32 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 7b: Adverse Events Measured Using the 20-item Negative Effects Questionnaire (NEQ-20)	5.7 score on scale Standard Deviation 8.2

PRIMARY outcome

Timeframe: Adherence data collected over the entire course of the treatment, up to 8 weeks.

Preregistered target: at least 50% of participants completing at least 2 exposure exercises

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 3: Adherence to the Protocol #2: Percentage of Participants Completing at Least 2 Exposure Exercises	32 Participants

PRIMARY outcome

Timeframe: Post-treatment assessment (immediately after treatment, completed within 45 days)

The respondent was instructed to describe up to three adverse events.

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=32 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Feasibility 7a: Adverse Events Measured Using Free-text Items #2: Number of Participants Who Reported at Least One Adverse Event	5 Participants

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), weekly during treatment, Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-30, higher score indicates more distressing physical symptoms

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Patient Health Questionnaire-15 (PHQ-15)	-4.2 units on a scale Interval -5.5 to -2.9

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), weekly during treatment, Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-48, higher score indicates higher degree of preoccupation with symptoms

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Somatic Symptom Disorder-B Criteria Scale (SSD-12)	-13.0 Likert scale units Interval -16.5 to -9.4

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), weekly during treatment, Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Under development, higher score indicates higher degree of preoccupation with symptoms. This is to be regarded as an item pool that will be further analyzed in 2024-2025, and in conjunction with data from other clinical trials. As of September 2023, it is therefore not yet possible to provide a theoretical range for this scale, and it is also not possible to provide outcomes.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-42, higher score indicates more health anxiety

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
14-item Health Anxiety Inventory (HAI-14)	-6.7 Likert scale units Interval -9.3 to -4.2

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), post-treatment assessment Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-64, higher score indicates more anxiety sensitivity

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Anxiety Sensitivity Index (ASI)	-9.5 Likert scale units Interval -13.1 to -6.0

SECONDARY outcome

Timeframe: Pre-treatment assessment (within 2 weeks before treatment), post-treatment assessment Post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-21, higher score indicates more general anxiety

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
GAD-7	-3.4 Likert scale units Interval -5.0 to -1.7

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), weekly during treatments (suicidality), post-treatment assesment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-27, higher score indicates more symptoms of depression

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Patient Health Questionnaire (PHQ-9)	-3.2 units on a scale Interval -4.6 to -1.8

SECONDARY outcome

Timeframe: Screening, pre-treatment assessment (within 2 weeks before treatment), post-treatment assessment (immediately after treatment, completed within 45 days), 3 months after treatment

Change pre-post, as derived from linear mixed effects regression models fitted by maximum likelihood estimation using data from all 33 participants, and fitted on all 11 measurement points over the treatment phase (from pre-treatment to post-treatment). Theoretical range: 0-100, higher score indicates more disability

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
12-item WHO Disability Assessment Schedule 2.0 (WHODAS 2.0)	-8.8 units on a scale Interval -13.0 to -4.6

SECONDARY outcome

Timeframe: Screening only

Theoretical range: 0-40, higher score indicates more problematic alcohol use

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Alcohol Use Disorders Identification Test (AUDIT)	4.7 score on a scale Standard Deviation 5.7

SECONDARY outcome

Timeframe: Screening only

Theoretical range: 0-44, higher score indicates more problematic substance use

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Drug Use Disorders Identification Test (DUDIT)	0.2 score on a scale Standard Deviation 0.8

SECONDARY outcome

Timeframe: Week 3 of treatment

Theoretical range: 6-42, higher score indicates better relationship with the therapist

Outcome measures

Measure	Internet-delivered Exposure-based Treatment n=33 Participants Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Working Alliance Inventory (WAI)	35.2 score on a scale Standard Deviation 5.7

Adverse Events

Internet-delivered Exposure-based Treatment

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Measure	Internet-delivered Exposure-based Treatment n=32 participants at risk；n=33 participants at risk Eight weeks of therapist-guided exposure-based treatment delivered via the Internet. Exposure: Systematic confrontation with stimuli associated with symptom-related distress, to achieve therapeutic changes in cognitions or behavior
Psychiatric disorders increased anxiety, stress or distress	9.4% 3/32 • 8-week treatment period We assessed adverse events using free-text items where the respondent was instructed to describe up to three adverse events and rate how much this affected them at the time it occurred and at post treatment. We also administered the 20-item Negative Efects Questionnaire (NEQ-20). The reason why 32 (not 33) is reported as the number at risk for the "other" subtype of adverse events is that these data were derived from a post-treamtent questionnaire that was completed by 32/33 participants.
Psychiatric disorders a negative outlook on the future caused by poor treatment outcome	3.1% 1/32 • 8-week treatment period We assessed adverse events using free-text items where the respondent was instructed to describe up to three adverse events and rate how much this affected them at the time it occurred and at post treatment. We also administered the 20-item Negative Efects Questionnaire (NEQ-20). The reason why 32 (not 33) is reported as the number at risk for the "other" subtype of adverse events is that these data were derived from a post-treamtent questionnaire that was completed by 32/33 participants.
Psychiatric disorders distress caused by conflicting information on how to optimise the effect of meditation	3.1% 1/32 • 8-week treatment period We assessed adverse events using free-text items where the respondent was instructed to describe up to three adverse events and rate how much this affected them at the time it occurred and at post treatment. We also administered the 20-item Negative Efects Questionnaire (NEQ-20). The reason why 32 (not 33) is reported as the number at risk for the "other" subtype of adverse events is that these data were derived from a post-treamtent questionnaire that was completed by 32/33 participants.

Additional Information

Dr. Erland Axelsson

Karolinska Institutet

Phone: 0706171039

Email: erland.axelsson@ki.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place