Exploring Immunological Markers Associated With Mental Fatigue in Graves' Disease

NCT05678374 | Recruiting

• 1 other identifier: ImmunoGraves WP1
• Study Type: observational
• Target: 180
• Locations: 1 country
• Sites: 1

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.

Conditions

Graves Disease; Graves Ophthalmopathy; Mental Fatigue; Autoimmune Diseases; Thyroid Diseases

Keywords

Biomarkers; Cerebrospinal fluid in Graves' disease

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (15)

• 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

  Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.

• 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

  Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.

• Thyroid autoantibodies compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls

  Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.

• Cytokines compared between Graves' disease complicated by mental fatigue, Graves' disease not complicated by mental fatigue and healthy controls

  Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.

• 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

  Patients and controls will be examined at one occasion, for patients 15-60 months after diagnosis of Graves' disease.

Study Arms (3)

Graves' patients with mental fatigue

Women diagnosed with Graves 15 moths to 60 months ago with Mental Fatigue Scale score of more than 13 (maximum 42, cut of 10,5 for mental fatigue)

Graves' patients without mental fatigue

Women diagnosed with Graves 15 moths to 60 months ago with Mental Fatigue Scale score of less than 8 (maximum 42, cut of 10,5 for mental fatigue)

Thyroid healthy controls without mental fatigue

Women without current or previous thyroid disease and with Mental Fatigue Scale scores of less than 8

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Vastra Gotaland Region: lead

Study Sites (1)

Department of Endocrinology, Sahlgrenska University Hospital

Gothenburg, 41346, Sweden

RECRUITING

MeSH Terms

Conditions

Graves Disease; Graves Ophthalmopathy; Mental Fatigue; Autoimmune Diseases; Thyroid Diseases

Condition Hierarchy (Ancestors)

Exophthalmos; Orbital Diseases; Eye Diseases; Goiter; Endocrine System Diseases; Hyperthyroidism; Immune System Diseases; Eye Diseases, Hereditary; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Fatigue; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior

Study Officials

• Helena Filipsson

  Institute of Medicine, Sahlgrenska Academy, University of Gothenburg

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karin Tammelin

CONTACT

+46313427331; karin.tammelin@vgregion.se

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 19, 2022
• First Posted: January 10, 2023
• Study Start: October 1, 2019
• Primary Completion (Estimated): December 20, 2028
• Study Completion (Estimated): December 20, 2028
• Last Updated: September 29, 2025

Record last verified: 2025-09

Locations

SE (1)