Central Processing of Odour Stimuli in Patients With Functional Somatic Disorder, MCS or Post Covid Compared to Healthy Controls

NCT04935307 | Active Not Recruiting

• 1 other identifier: 1-10-72-273-20 MR pilot
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Functional somatic disorders (FSD) are frequent in all medical settings and characterized by persistent physical symptoms that cannot be explained by other somatic or psychiatric conditions. In recent decades, a number of different types of functional somatic disorders have been defined, but so far there is no clear explanation for the pathophysiology. The high prevalence of olfactory problems in some patients with FSD suggests that olfactory symptoms are a potential diagnostic biomarker, especially in patients with multiple chemical sensitivity (MCS) and/ or post-covid. The olfactory system is a unique sense with direct pathways to the limbic system, which is associated with emotion and mood. The focus on the olfactory system has revealed a significant association of this sense with numerous diseases. Hypotheses:

• Patients with MCS and FSD have normal olfactory tests (normosmic subjects according to TDI score using "sniffing test") but differ in habituation test compared to healthy controls.
• MCS, post-covid and FSD patients have different odour perception processing in the brain as a "fingerprint" of functional somatic disorder compared to healthy controls. Research plan: The aim of this parts of the study is to identify specific MRI and paraclinical measures for MCS, post covid and BDS. In the first phase, 5 patients with MCS and 5 healthy controls will have a full clinical test of the olfactory system at the Flavour Institute, AU. In addition, they will be scanned (for "fingerprinting") where the investigators expect to find changes in olfactory connectivity similar to those seen in depression. This phase of the study will lead to a conclusion on the exact MR parameters to be used in the main study. In the second phase of the study, 10 patients with MCS, 10 with post-covid, 10 with FSD, and 10 healthy controls will be evaluated using a test battery of questionnaires and paraclinical tests. Perspectives: Previous imaging studies have focused on pain stimulation paradigms, rest-state fMRI, and DTI, but the olfactory system may be the "missing link" in identifiying a quantitative candidate in terms of whole-brain computational modeling and could potentially be used as a "fingerprint" in diagnosis and treatment monitoring.

Conditions

Functional Disorder; Bodily Distress Syndrome; Multiple Chemical Sensitivity; Post COVID-19

Outcome Measures

Primary Outcomes (2)

• "Fingerprinting"

  The investigators seek to employ whole-brain computational modeling based on MRI-derived functional and structural connectomes. The investigators will use the 3T MR Siemens® scanner that is situated at Aarhus University Hospital. A T1 structural image sequence will be run to obtain an image for later co-registration. After scanning data analyses including pre-processing, first-level analyses, and higher-level analyses will carry out.

  Through study completion, an average of 6 months

• "Sniffing Stick test"

  The standardized psychophysical olfactory test, the "Sniffing Stick" test; will be performed on all three groups of participants before the scanning session. This battery of tests consists of odor threshold (T), discrimination (D), and identification (I) parts. The total score (TDI) was determined by the sum of the three scores (T+D+I). Habituation test; In order to test the flexible hedonic evaluation of odors in MCS and BDS compare to healthy controls the investigators will carry out habituation tests. The evaluation task asks the participant to rate the odors pleasantness, all individuals responses will be arranged by Likert scale 1-5.

  Through study completion, an average of 6 months.

Secondary Outcomes (3)

• Pain thresholds

  Through study completion, an average of 3 months.

• Heart Rate Variability

  Through study completion, an average of 6 months.

• Cognitive testing

  Through study completion, an average of 6 months.

Study Arms (4)

Patients with multiple chemical sensitivity (MCS)

EXPERIMENTAL

MCS is characterized by odour intolerance and various somatic symptoms attributed to the influence of toxic environmental chemicals in low usually harmless doses.

Diagnostic Test: MRI and paraclinical tests

Patients with multi-systemic functional somatic disorders (FSD)

EXPERIMENTAL

Based on empirical research, a phenotype of multi-systemic FSD or multi-organ bodily distress syndrome (multi-organ BDS) has been identified in the most severely affected patients who have symptoms from multiple organ systems, thus fulfilling the criteria for multiple FSS. Multi-organ BDS is a research diagnosis, and the terms FSD and BDS are used as synonyms. This diagnosis is defined by an identifiable physical symptom pattern with symptoms from four groups (a cardiopulmonary, a gastrointestinal, a musculoskeletal, and a general symptom group).

Diagnostic Test: MRI and paraclinical tests

Healthy controls

EXPERIMENTAL

Healthy participants

Diagnostic Test: MRI and paraclinical tests

Patients with post-covid

EXPERIMENTAL

Post covid is according to WHO characterized by continuation og development of new symptom 3 months after the initial SARS-CoV-2 infection, with these symptoms lasting for at least 2 months with no other explanation. Symptoms include fatigue, shortness of breath and cognitive dysfunction over 200 different symptoms have been reported that can have an impact on everyday functioning.

Diagnostic Test: MRI and paraclinical tests

Interventions

MRI and paraclinical tests DIAGNOSTIC_TEST

The patients and controls will be evaluated using MRI and furthermore a large test battery of questionnaires and paraclinical tests. Including the following test: MCS checklist, BDS-Checklist, Symptom Checklist-92 (SCL-92), Whiteley-8, SF-36, Major Depression Inventory (MDI), GAD-10 anxiety scale, and related questionnaire, behavioral olfactory test (TDI), habituation test, pain measurement thresholds tests, Heart Rate Variability and cognitive testing.

Healthy controls; Patients with multi-systemic functional somatic disorders (FSD); Patients with multiple chemical sensitivity (MCS); Patients with post-covid

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female patients and healthy controls 18-70 years old.
• Patients with moderate or severe MCS or multi-organ BDS or post-covid.
• Symptoms present \>6 months.
• Written and verbal informed consent and letter of authority.

You may not qualify if:

• Before the beginning of the study; Current sinonasal illness or upper respiratory tract allergy.
• Serious or unstable medical illness (e.g. Apoplexy, Parkinson's, Alzheimer's disease, ischemic extremity pain, renal failure, liver failure, epilepsy, and Raynaud's phenomenon) that is confirmed by medical history and, if possible, compared to medical records.
• Current and previous diagnosis of mania, bipolar disorder, psychosis, severe agitation, imminent deliria, current suicide risk, alcohol or drug dependence (ICD-10). Confirmed by psychiatric history and, if possible, compared to psychiatric or medical records.
• Pregnancy and lactation.
• MR \& MEG scanner incompatibility, assessed by an MR/MEG control questionnaire.
• After the beginning of the study;
• MRI diagnosis of incidental pathologic findings; Lesions, Hemorrhage, etc.
• The onset of acute depression or serve anxiety. Relevant transference to treatment option should be initiated immediately.
• Suicide risk (treatment will be initiated immediately).
• Pregnancy and lactation.
• The patient wishes to leave the study.
• The patient cannot co-operate during the examination.

Sponsors & Collaborators

• University of Aarhus: lead

Study Sites (1)

The Research Clinic for Functional Disorders

Aarhus, 8000, Denmark

Location

MeSH Terms

Conditions

Multiple Chemical Sensitivity

Interventions

Magnetic Resonance Imaging

Condition Hierarchy (Ancestors)

Environmental Illness; Hypersensitivity; Immune System Diseases; Disorders of Environmental Origin

Intervention Hierarchy (Ancestors)

Tomography; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis

Study Officials

• Lise Gormsen, PhD

  Functional Disorders

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: DIAGNOSTIC
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The aim of this study is to identify specific MRI and paraclinical measures for multiple chemical sensitivity (MCS), multi-organ bodily distress syndrome (multi-organ BDS) and post covid compared to Healthy controls

Study Record Dates

• First Submitted: June 9, 2021
• First Posted: June 23, 2021
• Study Start: November 2, 2021
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)