Graves DiseaseNCT06081439
Validating Immunological Markers Associated With Mental Fatigue in Graves' Disease
An observational study of Graves Disease and Mental Fatigue, run by Vastra Gotaland Region at 1 site in Sweden.
Trial summary
Mental fatigue occurs in many diseases and the reasons are mostly unknown. The investigators hypothesize that remaining mental fatigue after restored euthyroidism in Graves' disease is an autoimmune complication. Read more about this study
- Who is it for?
- Ages 18 to 72 years
- Conditions the study is for
- Graves Disease, Mental Fatigue
- How many people
- 430 participants
- Where
- 1 siteSweden
- Study dates
- 12 Sep 2019to 20 Dec 2030
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 72 years
- All sexes
- Adult, Older adult
Study population: 310 patients with Graves' are recruited from Endocrine Clinic at Sahlgrenska University Hospital and Östra Hospital. Patients meeting the inclusion criteria are consecutively asked to participate. A subgroup of maximum 120 patients who are willing to give cerebrospinal fluid are recruited to the sub-study with magnetoencephalography. Controls to this sub-study are recruited from records from the tax authority.
Who may be able to join
- Recently diagnosed Graves' disease
- Positive thyroid stimulating hormone (TSH)-receptor antibodies (TRAb)
- Thyroid hormones above the upper reference limit
- Inclusion within three weeks after start of antithyroid drugs
- Controls: Matched for gender and age
Who cannot join
- Person unable to follow protocol as with psychosis, dementia or not able to answer questionnaires in Swedish.
- Recidive of Graves' disease
- Pregnancy
- Controls: -Thyroid disease
- Neurological disease
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Helena Filipsson, ass prof contact
Sweden1 site, 1 recruiting
- Recruiting
Endokrina Forskningsenheten, Sahlgrenska University Hospital
Gothenburg, 41346
Karin Tammelin, PhD student, +46313427331, karin.tammelin@vgregion.se
About this study
Official title: Validating Immunological Markers in Blood and Cerebrospinal Fluid Associated With Mental Fatigue in Graves' Disease and Their Association With Functional Changes in Neuronal Activation
Mental fatigue occurs in many diseases and the reasons are mostly unknown. The investigators hypothesize that remaining mental fatigue after restored euthyroidism in Graves' disease is an autoimmune complication. This is a confirmatory study of the biomarkers from ImmunoGraves WP1 in which immunological markers with possible association with mental fatigue in Graves' disease are explored.
In ImmunoGraves WP2, 310 patients with Graves' disease are assessed for symptoms of mental fatigue, quality of life, anxiety and depression, self-evaluated stress, coping strategies, personality traits, eye symptoms and background variables. Participants are examined in hyperthyroidism at inclusion, within three weeks from diagnosis, and in euthyroidism after 15 months. Serum and cerebrospinal fluid (in a subsample of participants) is collected at both visits and will be evaluated for the immunological markers identified in WP1 as well as for thyroid hormones, thyroid autoantibodies and biomarkers indicating organic and structural nerve damage. Significant predictors for mental fatigue will be identified by logistic regression.
To assess functional changes in the brain, magnetoencephalography will be performed in a subset of patients and in healthy controls at inclusion and after 15 to 18 months. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation during attention testing.
- Conditions
- Graves Disease, Mental Fatigue
- Medical subject headings
- Graves Disease, Mental Fatigue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| patients | 310 | |
| controls | 120 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Identifying the immunological markers in blood at inclusion that significantly increases the risk for mental fatigue at follow up.
Immunological markers in blood identified in the on-going study ImmunoGraves Wp1 are analysed between participants who at follow up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Secondary outcomes (31)
Levels of the previously identified immunological markers in serum at inclusion compared between participants who at follow up have high scores at the Mental Fatigue Scale and participants who at follow up have low scores at the Mental Fatigue Scale
Immunological markers identified in the on-going study ImmunoGraves Wp1 are compared between participants who at follow up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of the previously identified immunological markers in cerebrospinal fluid at inclusion compared between patients with high and low scores at the Mental Fatigue Score at follow-up
Immunological markers identified in the on-going study ImmunoGraves Wp1 are compared between participants who at follow up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Cerebrospinal fluid drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion
Levels of the previously identified immunological markers in serum at follow up compared between patients with high and low scores at the Mental Fatigue Scale at follow-up and to healthy controls
Immunological markers identified in the on-going study ImmunoGraves Wp1 are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of the previously identified immunological markers in cerebrospinal fluid at follow up compared between patients with high and low scores at the Mental Fatigue Scale at follow-up
Immunological markers identified in the on-going study ImmunoGraves Wp1 are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Cerebrospinal fluid drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of thyroid hormones at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at follow-up
Levels of thyroid hormones, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of thyroid hormones at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at inclusion
Levels of thyroid hormones, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at inclusion have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
Levels of thyroid antibodies at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at follow-up
Levels of thyroid autoantibodies, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of thyroid antibodies at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at inclusion
Levels of thyroid autoantibodies, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale at inclusion. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
Levels of thyroid antibodies at follow-up compared in patients with high and low scores at the Mental Fatigue Scale at follow-up.
Levels of thyroid autoantibodies, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of biomarkers indicating organic and structural nerve damage at inclusion in patients with high and low scores at the Mental Fatigue Scale at follow-up
Levels of biomarkers indicating organic and structural nerve damage, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood and, in a subgroup, cerebrospinal fluid drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Levels of biomarkers indicating organic and structural nerve damage at inclusion in patients with high and low scores at the Mental Fatigue Scale at inclusion
Levels of biomarkers indicating organic and structural nerve damage, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at inclusion have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood and, in a subgroup, cerebrospinal fluid, drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
Levels of biomarkers indicating organic and structural nerve damage at follow-up in patients with high and low scores at the Mental Fatigue Scale at follow-up
Levels of biomarkers indicating organic and structural nerve damage, analysed with the standard method of the laboratory at Sahlgrenska University Hospital, compared between participants who at follow up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Blood and, in a subgroup, cerebrospinal fluid, drawn at follow-up after 15 months. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Prevalence of endocrine ophthalmopathy at inclusion compared between patients with high and low scores at the Mental Fatigue Scale at follow-up
Endocrine ophthalmopathy defined as Clinical Activity Score of 3/7 or more, compared between participants who at follow up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Higher scores at the Clinical Activity Score means more serious endocrine ophthalmopathy.
Measured: Patients examined at inclusion, Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Prevalence of endocrine ophthalmopathy at follow-up compared between patients with high and low scores at the Mental Fatigue Scale at follow-up
Endocrine ophthalmopathy defined as Clinical Activity Score of 3/7 or more, compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue. Higher scores at the Clinical Activity Score means more serious endocrine ophthalmopathy.
Measured: Patients examined and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Scores at the Mental Fatigue Scale at inclusion compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
Scores at the Mental Fatigue Scale at inclusion compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.
Measured: Mental Fatigue Scale completed by participants at inclusion and follow-up at 15 months after inclusion, by controls at inclusion.
Self-evaluated quality of life in relation to ophthalmopathy compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls.
Evaluated by the validated questionnaire the Graves' Ophthalmopathy Quality of Life Questionnaire (GO QoL). Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue. Higher scores at the Graves' Ophthalmopathy Quality of Life Questionnaire means better quality of life.
Measured: Graves' Ophthalmopathy Quality of Life Questionnaire and Mental Fatigue Scale completed by participants at inclusion and follow-up at 15 months after inclusion, by controls at inclusion.
Self-evaluated quality of life in relation to thyroid symptoms will be compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls.
Evaluated by the validated questionnaire Thyroid-specific Patient-Reported Outcome short-form (ThyPro 39). Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue.Higher scores at the Thyroid-specific Patient-Reported Outcome short-form means worse quality of life.
Measured: Thyroid-specific Patient-Reported Outcome short-form and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
Self-evaluated quality of life and well-being will be compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
Evaluated by the validated questionnaire Psychological General Well Being index (PGWB). Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue. Higher scores at the Psychological General Well Being means higher quality of life.
Measured: Psychological General Well Being indexed Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
Self-evaluated symptoms of anxiety and depression compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
Evaluated by the validated questionnaire the Comprehensive Psychopathological Rating Scale (CPRS). Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Mental Fatigue Scale means more brain fatigue. Higher scores at the Comprehensive Psychopathological Rating Scale mean more symptoms of anxiety and depression.
Measured: Comprehensive Psychopathological Rating Scale and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
Self-evaluated stress compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
Evaluated by the validated questionnaire Perceived Stress Scale (PSS-14). Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the Perceived Stress Scale mean more symptoms of stress.
Measured: Perceived Stress Scale and Mental Fatigue Scale completed by participants at inclusion and follow up 15 months after inclusion, by controls at inclusion.
Coping strategies will be compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls
Evaluated by the validated questionnaire Brief cope. Coping strategies are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.
Measured: Brief cope and Mental Fatigue Scale completed by participants at inclusion and follow up 15 months after inclusion, by controls at inclusion.
Optimistic self-beliefs to cope with difficulties in life will be compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls.
Evaluated by the validated questionnaire General Self-Efficacy. Scores are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale. Higher scores at the General Self-Efficacy questionnaire means higher optimistic self-beliefs.
Measured: General self efficacy and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
Personality traits will be compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls
Evaluated by the validated questionnaire NEO Five-Factor Inventory-3 (NEO-FFI-3). Personality traits are compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.
Measured: NEO Five-Factor Inventory-3 and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
Observations of hippocampal neuronal activation during attention testing in hyperthyroidism and in healthy controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing.
Measured: Magnetoencephalography will be performed in patients and in controls at inclusion.
Observations of neuronal activation during attention testing in patients with Graves' disease at follow-up and in healthy controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing.
Measured: Magnetoencephalography will be performed in patients at follow-up 15 months after inclusion, in controls at inclusion.
Observations of neuronal activation during attention testing at follow-up compared between patients with and without mental fatigue and in healthy controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. The alfa- and theta-band oscillations will be compared between participants who at follow-up have 10.5 points or more at the Mental Fatigue Scale and participants who have less than 10.5 points at the Mental Fatigue Scale.
Measured: Magnetoencephalography will be performed in patients after 15 months, in controls at inclusion. Mental Fatigue Scale will be completed by patients at follow-up 15 months after inclusion, by controls at inclusion.
Immunological markers from Primary Outcome will be compared in patients with changed hippocampal neuronal activation compared to controls, and in controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. Immunological markers identified in the on-going study ImmunoGraves wp1 and in Primary Outcome.
Measured: Magnetoencephalography will be performed in patients at inclusion and after 15 month, in controls at inclusion. Blood and cerebrospinal fluid will be drawn at inclusion.
Immunological markers from Primary Outcome will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. Immunological markers identified in the on-going study ImmunoGraves wp1 and in Primary Outcome.
Measured: Magnetoencephalography will be performed in patients at inclusion and after 15 months, in controls at inclusion. Blood and cerebrospinal fluid will be drawn at inclusion.
Biomarkers indicating organic and structural nerve damage will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. Biomarkers indicating organic and structural nerve damage analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Measured: Magnetoencephalography will be performed in patients at inclusion and at follow-up 15 months after inclusion, in controls at inclusion. Blood and cerebrospinal fluid will be drawn at inclusion.
Thyroid autoantibodies will be compared in patients with changed hippocampal neuronal activation compared to controls, and in controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. Thyroid autoantibodies analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Measured: Magnetoencephalography will be performed in patients at inclusion and after 15 months, in controls at inclusion. Blood and cerebrospinal fluid will be drawn at inclusion.
Thyroid autoantibodies will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
Magnetoencephalography will be performed in a subset of patients and in healthy controls. Combined with magneto resonance imaging (MRI), magnetoencephalography gives information on neuronal activation by measuring alfa- and theta-band oscillations during attention testing. Thyroid autoantibodies analysed with the standard method of the laboratory at Sahlgrenska University Hospital.
Measured: Magnetoencephalography will be performed in patients at inclusion and after 15 months, in controls at inclusion. Blood and cerebrospinal fluid will be drawn at inclusion.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2023
- Study start12 Sep 2019
- Primary completion20 Dec 2029 (estimated)
- Study completion20 Dec 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Graves DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 430 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Vastra Gotaland Region
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Helena Filipsson, ass prof, Principal investigator, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Department of Endocrinology, Sahlgrenska University Hospital, Wallenberg Center for Molecular and Translational Medicine, all in Gothenburg, Sweden
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06081439
- Sponsor's protocol ID
- ImmunoGraves wp2
- Status last verified
- Sep 2026
- First submitted
- 28 Sep 2023
- Last updated
- 10 Sep 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No