Auto-immune Contribution in Symptom-based Sensory and Autonomic Disorders
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-80
SponsorKing's College London
About this trial
Postural Orthostatic Tachycardia Syndrome (PoTS) is a condition where the heart rate increases when standing up, causing symptoms like dizziness and fainting. It primarily affects young women and can be very disabling, impacting daily life. In addition to the typical symptoms related to standing, people with PoTS also experience unexplained pain and fatigue, which worsen their quality of life. The exact causes of PoTS are still unknown, but it is often triggered by viral infections and some PoTS patients show signs of immune system involvement, such as the presence of certain autoantibodies and other autoimmune conditions. Research on other chronic pain disorders, including fibromyalgia syndrome (FMS), has found that autoantibodies can cause pain by affecting how the nerves work. This study aims to investigate if similar immune-related mechanisms are behind the widespread pain seen in PoTS. This study will also look at how PoTS affects the nervous system by testing nerve activity in participants and assessing the number of nerve fibres in the skin, to check if similar changes can be seen in mice. This study will also involve participants with fibromyalgia syndrome and healthy volunteers.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
Between 18 and 80 years of age.
In the capacity to understand and sign an Informed Consent Form.
Willing and able to comply with scheduled visits and study procedures.
PoTS: following Heart Rhythm Society Expert Consensus Statement criteria, 2015, with or without comorbid FMS.
Disqualifiers
Previous diagnosis of an established autoimmune condition or dermatological conditions affecting skin afferents (e.g. psoriasis, lupus, vitiligo, dermatitis…).
Application of local anaesthetics or steroid injections within 35 days prior to the microneurography visit.
Current use of anticoagulant therapy.
History of peripheral neuropathy or conditions usually associated with peripheral neuropathy, such as Diabetes Mellitus, Vitamin B12 deficiency, Lyme disease, a screen positive for hepatitis B surface antigen, hepatitis C virus antibody, or antibodies against human immunodeficiency viruses 1 and 2.
Trial population
100 patients diagnosed with PoTS (50% with comorbid FMS) 50 patients diagnosed with FMS without dysautonomia Up to 100 healthy volunteers
Trial design
Design model
Other
Time perspective
Prospective
Treatments tested in this trial
Questionnaire and Physical Exam
Other interventionStandardised participant questionnaires assessing neurological symptoms, including pain (NPSI, DN4, BPI), fatigue (Fatigue Severity Scale), depression and anxiety (PHQ9 and GAD7) and autonomic dysfunction (Malmo PoTS Score and COMPASS-31).
Nerve conduction studies
Diagnostic testMeasures how fast an electrical impulse moves through sensory and motor nerves. The test will be used to identify/rule out large fibre peripheral neuropathy.
Microneurography
Diagnostic testElectrophysiological technique that can record action potentials from individual peripheral nerve axons in humans. The test will be used to identify/rule out small nerve fibre dysfunction.
Quantitative Sensory Testing
Diagnostic testMeasures psychophysical sensory perception in response to different types of stimuli, such as thermal, mechanical, pressure and vibration. The test will be used to identify/rule out nerve fibre dysfunction, by generating a quantitative sensory profile of different sensory modalities.
Skin biopsy
Diagnostic testSafe and minimally invasive procedure to quantify intraepidermal nerve fibres density (IENFD). Reduced IENF density is associated with small fibre neuropathy.
Blood Product
Biological/VaccineA blood sample of a maximum of 120ml will be collected from a superficial upper limb vein. Blood aliquots (50ml tubes) will then be centrifuged to separate serum from the peripheral blood cells.
Treatment groups
250 Participants
are divided into 4 treatment groupsGroup A: PoTS with pain6 interventions
Group B: PoTS without pain6 interventions
Group C: FMS6 interventions
Group D: Healthy volunteers6 interventions
Trial outcomes
Primary outcomes
1
Evidence of immune-mediated pain mechanisms and autonomic dysfunction
To determine whether IgG antibodies from PoTS participants (with or without FMS) induce pain-like behaviours and autonomic abnormalities in mice, following passive transfer.
Time frame
From enrollment until passive tranfer experiments are performed.Secondary outcomes
1
Assessment of electrical activity recorded from nerve fibres in humans
To use microneurography to measure nerve activity in participants and identify patterns consistent with small nerve fibre dysfunction.
Time frame
From enrollment until Visit 1.2
Evidence of small fibre neuropathy (SFN)
To evaluate intra-epidermal nerve fibre density (IENFD) in skin biopsies from PoTS participants to identify signs of SFN; similar analysis will be conducted in mice receiving participants' IgG.
Time frame
From enrollment until passive tranfer experiments are performed.3
IgG binding to rodent neurons
To test whether IgG from participants' serum binds to neurons in vitro, using cell-based assays and immunofluorescence.
Time frame
From enrollment until passive tranfer experiments are performed.4
Correlation between participants symptoms and IgG effects in mice
To explore whether clinical symptom severity (e.g., pain, autonomic dysfunction) correlates with the degree of abnormality observed in mice after IgG transfer.
Time frame
From enrollment until passive tranfer experiments are performed.Locations
Sponsors and contacts
Click on the lead sponsor to view all of their trials.
King's College London
Lead sponsor
King's College Hospital NHS Trust
Collaborator
Guy's and St Thomas' NHS Foundation Trust
Collaborator
Source ClinicalTrials.gov
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