Auto-immune Contribution in Symptom-based Sensory and Autonomic Disorders

NCT06992531 | Not Yet Recruiting

• 1 other identifier: 352817
• Study Type: observational
• Target: 250
• Locations: 0 countries
• Sites: N/A

Brief Summary

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.

Conditions

Postural Orthostatic Tachycardia Syndrome (POTS); Fibromyalgia (FM)

Keywords

Postural orthostatic Tachycardia Syndrome; Fibromyalgia Syndrome; Widespread pain; Autoantibodies; Autonomic and sensory functions

Outcome Measures

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.

  From enrollment until passive tranfer experiments are performed.

Secondary Outcomes (4)

• Assessment of electrical activity recorded from nerve fibres in humans

  From enrollment until Visit 1.

• Evidence of small fibre neuropathy (SFN)

  From enrollment until passive tranfer experiments are performed.

• IgG binding to rodent neurons

  From enrollment until passive tranfer experiments are performed.

• Correlation between participants symptoms and IgG effects in mice

  From enrollment until passive tranfer experiments are performed.

Study Arms (4)

PoTS with pain

Participants with PoTS with an additional diagnosis of FMS

Other: Questionnaire and Physical Exam; Diagnostic Test: Nerve conduction studies; Diagnostic Test: Microneurography; Diagnostic Test: Quantitative Sensory Testing; Diagnostic Test: Skin biopsy; Biological: Blood Product

PoTS without pain

Participants with PoTS without pain

Other: Questionnaire and Physical Exam; Diagnostic Test: Nerve conduction studies; Diagnostic Test: Microneurography; Diagnostic Test: Quantitative Sensory Testing; Diagnostic Test: Skin biopsy; Biological: Blood Product

FMS

Participants with FMS without dysautonomia

Other: Questionnaire and Physical Exam; Diagnostic Test: Nerve conduction studies; Diagnostic Test: Microneurography; Diagnostic Test: Quantitative Sensory Testing; Diagnostic Test: Skin biopsy; Biological: Blood Product

Healthy volunteers

Healthy volunteers with no diagnosed autoimmune, chronic pain, or dysautonomia condition.

Other: Questionnaire and Physical Exam; Diagnostic Test: Nerve conduction studies; Diagnostic Test: Microneurography; Diagnostic Test: Quantitative Sensory Testing; Diagnostic Test: Skin biopsy; Biological: Blood Product

Interventions

Questionnaire and Physical Exam OTHER

Standardised 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).

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Nerve conduction studies DIAGNOSTIC_TEST

Measures how fast an electrical impulse moves through sensory and motor nerves. The test will be used to identify/rule out large fibre peripheral neuropathy.

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Microneurography DIAGNOSTIC_TEST

Electrophysiological 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.

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Quantitative Sensory Testing DIAGNOSTIC_TEST

Measures 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.

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Skin biopsy DIAGNOSTIC_TEST

Safe and minimally invasive procedure to quantify intraepidermal nerve fibres density (IENFD). Reduced IENF density is associated with small fibre neuropathy.

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Blood Product BIOLOGICAL

A 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.

FMS; Healthy volunteers; PoTS with pain; PoTS without pain

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

100 patients diagnosed with PoTS (50% with comorbid FMS) 50 patients diagnosed with FMS without dysautonomia Up to 100 healthy volunteers

You may qualify if:

• 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.
• Diagnostic criteria for participants:
• PoTS: following Heart Rhythm Society Expert Consensus Statement criteria, 2015, with or without comorbid FMS.
• FMS: following the American College of Rheumatology criteria 2016, with Fibromyalgia Impact Questionnaire (FIQ) exceeding 50, and with an average pain intensity exceeding 5.5.
• Healthy volunteers: no diagnosed autoimmune, chronic pain, or dysautonomia condition.

You may not qualify if:

• 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.
• Pregnancy.
• History of regular alcohol consumption (exceeding 14 units per week) or recent alcohol consumption exceeding 14 units per week over the last 6 months (14 units is equivalent to 7 pints \[568 mL/pint\] of beer at 3.6% alcohol by volume or 6 standard glasses \[176 mL/glass\] of wine at 12% alcohol by volume).
• Excessive consumption of caffeinated beverages (e.g., coffee, tea, cola, energy drinks), is defined as greater than 6 servings per day (1 serving/236 mL equals approximately 120 mg of caffeine).
• A history of drug abuse or addiction within 2 years before study, current regular or recreational use of marijuana (or any cannabis derivative).

Sponsors & Collaborators

• King's College London: lead
• King's College Hospital NHS Trust: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator

Biospecimen

Retention: SAMPLES WITHOUT DNA

Blood collection (Serum and Peripheral blood mononuclear cells) Skin biopsies

MeSH Terms

Conditions

Postural Orthostatic Tachycardia Syndrome; Fibromyalgia

Interventions

Surveys and Questionnaires; Restraint, Physical; Nerve Conduction Studies

Condition Hierarchy (Ancestors)

Orthostatic Intolerance; Primary Dysautonomias; Autonomic Nervous System Diseases; Nervous System Diseases; Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases

Intervention Hierarchy (Ancestors)

Data Collection; Epidemiologic Methods; Investigative Techniques; Health Care Evaluation Mechanisms; Quality of Health Care; Health Care Quality, Access, and Evaluation; Public Health; Environment and Public Health; Behavior Control; Therapeutics; Immobilization; Diagnostic Techniques, Neurological; Diagnostic Techniques and Procedures; Diagnosis; Electrodiagnosis

Central Study Contacts

David Andersson

CONTACT

+447986420716; david.andersson@kcl.ac.uk

Ana Ribeiro

CONTACT

+447768974020; anaribeiro@nhs.net

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2025
• First Posted: May 28, 2025
• Study Start: October 1, 2025
• Primary Completion (Estimated): October 1, 2029
• Study Completion (Estimated): October 1, 2030
• Last Updated: May 28, 2025

Record last verified: 2025-05