Clinical trial NCT06081439: Validating Immunological Markers Associated With Mental Fatigue in Graves' Disease
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
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Graves Disease
Mental Fatigue
Lead sponsor: Vastra Gotaland Region
Sponsor class: OTHER_GOV
First posted: 2023-10-13
Enrollment: 430
Sex: ALL
Minimum age (years): 18
Maximum age (years): 72
Standard ages: ADULT
OLDER_ADULT
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
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.

Brief 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. 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.


Eligibility criteria: Inclusion Criteria:

* 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

Exclusion Criteria:

* 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

Primary outcomes:
measure: Identifying the immunological markers in blood at inclusion that significantly increases the risk for mental fatigue at follow up.
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
Secondary outcomes:
measure: 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
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: 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
timeFrame: Cerebrospinal fluid drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion
measure: 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
timeFrame: Blood drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: 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
timeFrame: Cerebrospinal fluid drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: Levels of thyroid hormones at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at follow-up
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: Levels of thyroid hormones at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at inclusion
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
measure: Levels of thyroid antibodies at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at follow-up
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: Levels of thyroid antibodies at inclusion compared in patients with high and low scores at the Mental Fatigue Scale at inclusion
timeFrame: Blood drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
measure: Levels of thyroid antibodies at follow-up compared in patients with high and low scores at the Mental Fatigue Scale at follow-up.
timeFrame: Blood drawn and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: 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
timeFrame: Blood and, in a subgroup, cerebrospinal fluid drawn at inclusion. Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: 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
timeFrame: Blood and, in a subgroup, cerebrospinal fluid, drawn at inclusion. Mental Fatigue Scale completed by participants at inclusion.
measure: 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
timeFrame: 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.
measure: Prevalence of endocrine ophthalmopathy at inclusion compared between patients with high and low scores at the Mental Fatigue Scale at follow-up
timeFrame: Patients examined at inclusion, Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: Prevalence of endocrine ophthalmopathy at follow-up compared between patients with high and low scores at the Mental Fatigue Scale at follow-up
timeFrame: Patients examined and Mental Fatigue Scale completed by participants at follow-up 15 months after inclusion.
measure: 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
timeFrame: Mental Fatigue Scale completed by participants at inclusion and follow-up at 15 months after inclusion, by controls at inclusion.
measure: 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.
timeFrame: 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.
measure: 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.
timeFrame: 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.
measure: 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
timeFrame: Psychological General Well Being indexed Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
measure: Self-evaluated symptoms of anxiety and depression compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
timeFrame: Comprehensive Psychopathological Rating Scale and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
measure: Self-evaluated stress compared between patients with Graves' with and without mental fatigue at follow-up and to healthy controls
timeFrame: Perceived Stress Scale and Mental Fatigue Scale completed by participants at inclusion and follow up 15 months after inclusion, by controls at inclusion.
measure: Coping strategies will be compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls
timeFrame: Brief cope and Mental Fatigue Scale completed by participants at inclusion and follow up 15 months after inclusion, by controls at inclusion.
measure: 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.
timeFrame: General self efficacy and Mental Fatigue Scale completed by participants at inclusion and follow-up 15 months after inclusion, by controls at inclusion.
measure: Personality traits will be compared between patients with Graves' with and without mental fatigue at follow-up, and to healthy controls
timeFrame: 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.
measure: Observations of hippocampal neuronal activation during attention testing in hyperthyroidism and in healthy controls.
timeFrame: Magnetoencephalography will be performed in patients and in controls at inclusion.
measure: Observations of neuronal activation during attention testing in patients with Graves' disease at follow-up and in healthy controls.
timeFrame: Magnetoencephalography will be performed in patients at follow-up 15 months after inclusion, in controls at inclusion.
measure: Observations of neuronal activation during attention testing at follow-up compared between patients with and without mental fatigue and in healthy controls.
timeFrame: 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.
measure: Immunological markers from Primary Outcome will be compared in patients with changed hippocampal neuronal activation compared to controls, and in controls.
timeFrame: 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.
measure: Immunological markers from Primary Outcome will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
timeFrame: 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.
measure: Biomarkers indicating organic and structural nerve damage will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
timeFrame: 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.
measure: Thyroid autoantibodies will be compared in patients with changed hippocampal neuronal activation compared to controls, and in controls.
timeFrame: 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.
measure: Thyroid autoantibodies will be compared in patients without changed hippocampal neuronal activation compared to controls, and in controls.
timeFrame: 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.
Other outcomes:
Locations:
city: Gothenburg
country: Sweden
facility: Endokrina Forskningsenheten, Sahlgrenska University Hospital
Study officials:
affiliation: 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
name: Helena Filipsson, ass prof
role: PRINCIPAL_INVESTIGATOR
References: