Exploring Immunological Markers Associated With Mental Fatigue in Graves' Disease

Autoimmune Diseases Clinical Trial

Official title:

Exploring Immunological Markers in Blood and Cerebrospinal Fluid Associated With Mental Fatigue in Euthyroidism After Graves' Disease- a Cross Sectional Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05678374
• Other study ID #: ImmunoGraves WP1
• Status: Recruiting
• Start date: October 1, 2019
• Est. completion date: December 20, 2024

Study information

• Verified date: March 2024
• Source: Vastra Gotaland Region
• Contact: Karin Tammelin
• Phone: +46313427331
• Email: karin.tammelin[@]vgregion.se
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: December 20, 2024
• Est. primary completion date: December 20, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 72 Years

Eligibility

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

Related Conditions & MeSH terms

• Autoimmune Diseases
• Eye Diseases
• Fatigue
• Graves Disease
• Graves Ophthalmopathy
• Mental Fatigue
• Thyroid Diseases

Locations

Country	Name	City	State
Sweden	Department of Endocrinology, Sahlgrenska University Hospital	Gothenburg

Sponsors (1)

Lead Sponsor	Collaborator
Vastra Gotaland Region

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Each group will be analysed in arrays for antibodies targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to antibodies in mental fatigue patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Each group will be analysed in arrays for antibodies targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to antibodies in mental fatigue patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Each group will be analysed in arrays for Ab targeting 42000 human proteins (ScilifeLabs, Stockholm). Proteins binding to Ab in MF patients will be screened against the Human Protein Atlas (www.proteinatlas.org) and the Allen brain map (www.brain-map.org) and those expressed in the brain will be compared between groups.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Thyroid autoantibodies compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls	Levels of thyroid autoantibodies will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Cytokines compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls	Levels of cytokines will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Biomarkers will be analysed with the standard method of the laboratory at Sahlgrenska University Hospital.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Levels of autoantibodies to g-protein coupled receptors will be measured using enzyme-linked immunosorbent assays	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Prevalence of endocrine ophthalmopathy in Graves' complicated by mental fatigue compared to prevalence of endocrine ophtalmopathy in Graves' not complicated by mental fatigue	Prevalence defined as endocrine ophthalmopathy that has required assessment/and or follow up at ophthalmologist.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Evaluated by the validated questionnaire the Graves' Ophthalmopathy Quality of Life Questionnaire (GO QoL).	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Evaluated by the validated questionnaire Thyroid-specific Patient-Reported Outcome short-form (ThyPro 39)	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Self evaluated quality of life and well being will be compared between patients with Graves' with and without mental fatigue and to healthy controls	Evaluated by the validated questionnaire Psychological General Well Being index (PGWB)	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Self evaluated symptoms of anxiety and depression will be compared between patients with Graves' with and without mental fatigue and to healthy controls	Evaluated by the validated questionnaire the Comprehensive Psychopathological Rating Scale (CPRS).	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Self evaluated stress will be compared between patients with Graves' with and without mental fatigue and to healthy controls	Evaluated by the validated questionnaire Perceived Stress Scale (PSS-14).	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Coping strategies will be compared between patients with Graves' with and without mental fatigue and to healthy controls	Evaluated by the validated questionnaire Brief cope.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	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	Evaluated by the validated questionnaire General self efficacy.	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.
Secondary	Personality traits will be compared between patients with Graves' with and without mental fatigue and to healthy controls	Evaluated by the validated questionnaire NEO Five-Factor Inventory-3 (NEO-FFI-3).	Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.