Clinical trial NCT05678374: Exploring Immunological Markers Associated With Mental Fatigue in Graves' Disease
Official title: Exploring Immunological Markers in Blood and Cerebrospinal Fluid Associated With Mental Fatigue in Euthyroidism After Graves' Disease- a Cross Sectional Study
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Graves Disease
Graves Ophthalmopathy
Mental Fatigue
Autoimmune Diseases
Thyroid Diseases
Keywords: Biomarkers
Cerebrospinal fluid in Graves' disease
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2023-01-10
Enrollment: 180
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients are recruited from the both previous patients at the Endocrine outpatient Clinic at Sahlgrenska University Hospital in Gothenburg and from advertising. They are invited to a web based screening form where the ones eligible are contacted by study personal and eligibility criteria are checked again.

Controls are recruited by the same way and by contacting a random sample from the population registration (based on Swedish social security number).

Groups are matched for age, educational level and smoking habits.

Brief summary: Mental fatigue occurs in many diseases and the reasons are mostly unknown. The investigators hypothesize that remaining mental fatigue after restored hyperthyroidism in Graves' disease is an autoimmune complication. The aim of this study is to explore immunological markers possibly associated with mental fatigue in Graves' disease, which the investigators plan to validate in another study (ImmunoGraves wp 2).

Using a cross-sectional study design, mental fatigue is scored using a questionnaire to find 60 patients with and 60 without mental fatigue 15-60 months after diagnosis of Graves disease. The patients and 60 thyroid healthy controls without mental fatigue are assessed for thyroid hormones, quality of life, anxiety and depression, self-evaluated stress, coping strategies, eye symptoms and background variables. SciLifeLab in Stockholm, the national facility for autoimmune profiling, has pre-set large arrays including 42000 human proteins. Serum and cerebrospinal fluid will be separately pooled and analysed for a subgroup of patients with or without mental fatigue and for a subgroup of the control group. Proteins that preferably bind to antibodies in sera and/or cerebrospinal fluid from Graves' patients with mental fatigue in comparison to non-mental fatigue patients, will be screened against the Human Protein Atlas and the Allen brain map to identify those proteins that are expressed in the brain. Antibodies at higher concentration in the mental fatigue pools compared to the group without mental fatigue will be selected for further analyses on an individual level in the whole cohort together with antibodies targeting g-protein coupled receptors, thyroid autoantibodies, cytokines and biomarkers indicating organic and structural nerve damage.


Eligibility criteria: Inclusion Criteria

* If patient: Graves' disease with positive TSH-receptor antibodies and thyroid hormones above the upper reference limit at diagnosis
* Diagnosis15 to 60 months ago. If recidive both episodes must have occurred within 15 months to 60 months.
* Thyroid hormones within normal range without anti thyroid drugs
* If control: No thyroid disease
* Patient and control without mental fatigue: Mental Fatigue Score ≤8 (cut off 10.5)
* Patient with mental fatigue: Mental Fatigue Score \>13 and debut of symptoms of mental fatigue in parallel with debut of Graves' disease, without other obvious cause

Exclusion Criteria

* Person unable to follow protocol
* Multiple sclerosis, myalgic encephalomyelitis/chronic fatigue syndrome, any other neurological disease
* Traumatic brain injury with unconsciousness
* Other disease strongly associated with fatigue
* Pregnancy and breast-feeding
* On-going or recent systemic treatment with steroids
* Radioiodine therapy within the last 18 months

Primary outcomes:
measure: Identifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease complicated by mental fatigue than in Graves' disease not complicated by mental fatigue
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary outcomes:
measure: Identifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease complicated by mental fatigue than in thyroid healthy controls without mental fatigue
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Identifying autoantibodies targeting antigens occurring in the brain that are higher in Graves' disease not complicated by mental fatigue than in thyroid healthy controls without mental fatigue
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Thyroid autoantibodies compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Cytokines compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Biomarkers indicating organic and structural nerve damage compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Autoantibodies to other g-protein coupled receptors compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Prevalence of endocrine ophthalmopathy in Graves' complicated by mental fatigue compared to prevalence of endocrine ophtalmopathy in Graves' not complicated by mental fatigue
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Self evaluated quality of life in relation to ophthalmopathy will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Self evaluated quality of life in relation to thyroid symptoms will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Self evaluated quality of life and well being will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Self evaluated symptoms of anxiety and depression will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Self evaluated stress will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Coping strategies will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Optimistic self-beliefs to cope with difficulties in life will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
measure: Personality traits will be compared between patients with Graves' with and without mental fatigue and to healthy controls
timeFrame: Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Department of Endocrinology, Sahlgrenska University Hospital
Study officials:
affiliation: Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
name: Helena Filipsson
role: PRINCIPAL_INVESTIGATOR
References: